Journal Description
Journal of Molecular Pathology
Journal of Molecular Pathology
is an international, peer-reviewed, open access journal on every topic related to modern histopathology and cytopathology, predictive pathology and molecular cytopathology, published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within CAPlus / SciFinder, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 24.9 days after submission; acceptance to publication is undertaken in 3.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Latest Articles
Human Metastatic Melanoma Cell Lines Panel for In Vitro and In Vivo Investigations
J. Mol. Pathol. 2024, 5(1), 11-27; https://doi.org/10.3390/jmp5010002 - 08 Jan 2024
Abstract
►
Show Figures
The melanoma origin of cell lines obtained from the axillary lymph node (mel Kas, mel Pet, and mel Lap from patients with a verified diagnosis) was confirmed by the detection of the Melan A melanocyte marker expression. A hyperdiploid (2n+) for the mel
[...] Read more.
The melanoma origin of cell lines obtained from the axillary lymph node (mel Kas, mel Pet, and mel Lap from patients with a verified diagnosis) was confirmed by the detection of the Melan A melanocyte marker expression. A hyperdiploid (2n+) for the mel Kas line; near-diploid (2n), and in some cells near-tertaploid (4n), and even hypo-octaploid (8n) set (172–179 chromosomes) in the mel Pet cell line; and a hypotetraploid (4n−) for the mel Lap line were detected by karyotypic analysis. All three cell lines are tumorigenic; however, mel Pet demonstrates tumor growth in Balb/c nude mice only in the presence of matrigel. All three lines showed a high expression of TUBB3 and PD-L1 markers, while ERa was low (minimum for mel Pet). Significant differences in the expression level were shown for the Cyt molecular marker. In the transplantation of cells to Balb/c nude mice, a stable expression level is observed only for TUBB3. For the rest of the markers, a decrease in their expression level of varying degrees was noted when the cells were growing in solid tumors in vivo. Mutations were detected in oncogenes (BRAF, EZH2, KIT, KRAS, NRAS, ROS1) and tumor suppressor genes (CDKN2A, FAT4, KMT2C, LRP1B, PTEN, PTPRB, TP53). The detailed characterization of the cell lines makes them valuable for various scientific and regulatory experiments, particularly those involving preclinical data on antiproliferative drugs for malignant melanoma or investigations into melanoma cell properties and progression.
Full article
Open AccessArticle
Novel Approach to Proficiency Testing Highlights Key Practice Variations in Cancer Biomarker Delivery
by
, , , , , , , , and
J. Mol. Pathol. 2024, 5(1), 1-10; https://doi.org/10.3390/jmp5010001 - 05 Jan 2024
Abstract
►▼
Show Figures
Biomarkers are fundamental to modern oncology practice, forming a close link to pathology practice. Pathology results must be accurate, timely, comprehensive, and comprehendible. External proficiency testing is a key tool in maintaining biomarker quality. Here, we demonstrate the feasibility and utility of a
[...] Read more.
Biomarkers are fundamental to modern oncology practice, forming a close link to pathology practice. Pathology results must be accurate, timely, comprehensive, and comprehendible. External proficiency testing is a key tool in maintaining biomarker quality. Here, we demonstrate the feasibility and utility of a novel end-to-end proficiency testing exercise exploring accuracy, turnaround time, and communication. Challenge specimens were made using resected colon cancer tissue, each paired with a fictional clinical vignette, and distributed to participants who were asked to provide all molecular testing required and return a final report for each case upon completion. Reports were redistributed to an assessor team including medical oncologists, each of whom was asked to recommend a systemic therapy based on each lab’s biomarker report. Participants were graded based on their ability to guide oncologists to the correct treatment. Eight laboratories participated. Three laboratories were found to have suboptimal results, two leading oncologists to incorrect therapeutic prescriptions, and one withdrawn. Turnaround time ranged from 6 to 86 days (median 24). Substantial qualitative reporting differences were identified. This study demonstrates the feasibility of end-to-end proficiency testing. The approach provides considerable value beyond analytic accuracy, including specimen management, turnaround time, and communication of results. Results suggest that reporting differences may lead to treatment disparities. This style of quality assurance will help reinforce good practices critical to the delivery of precision cancer care.
Full article
Figure 1
Open AccessReview
DRP1 Regulation as a Potential Target in Hypoxia-Induced Cerebral Pathology
by
, , , , , , , and
J. Mol. Pathol. 2023, 4(4), 333-348; https://doi.org/10.3390/jmp4040027 - 09 Dec 2023
Abstract
►▼
Show Figures
The following review considers current concepts concerning the characteristics of DRP1-related mitochondrial division in brain cells during hypoxic-ischemic pathology. The functional role of DRP1 in neurons and astroglia in cerebral ischemia conditions was analyzed. We discuss the potential for regulating DRP1 activity through
[...] Read more.
The following review considers current concepts concerning the characteristics of DRP1-related mitochondrial division in brain cells during hypoxic-ischemic pathology. The functional role of DRP1 in neurons and astroglia in cerebral ischemia conditions was analyzed. We discuss the potential for regulating DRP1 activity through the selective inhibitor of mitochondrial fission, mdivi-1. The article also presents data on DRP1 involvement in astro- and microglia-mediated intercellular mitochondrial transport. Understanding of the molecular mechanisms responsible for mitochondrial fission during hypoxic-ischemic exposure will allow us to consider DRP1 as an effective therapeutic target for treating conditions with a hypoxic component.
Full article
Figure 1
Open AccessReview
The Role of Macrophages in Cardiac Function and Disease
by
and
J. Mol. Pathol. 2023, 4(4), 318-332; https://doi.org/10.3390/jmp4040026 - 07 Dec 2023
Abstract
►▼
Show Figures
A tight association between inflammation and cardiac damage has been extensively recognized. In this review, we will focus on macrophages as key players in the physiology and pathology of the heart and on their role in the functional crosstalk between inflammation and heart
[...] Read more.
A tight association between inflammation and cardiac damage has been extensively recognized. In this review, we will focus on macrophages as key players in the physiology and pathology of the heart and on their role in the functional crosstalk between inflammation and heart disease. In the steady state, macrophages contribute to the homeostasis of cardiac tissue. Indeed, cardiac resident macrophages promote coronary development and tissue homeostasis, favor electric conduction in cardiomyocytes, and contribute to mitochondrial quality control. However, macrophages also take part in adverse cardiac events contributing to the development or the progression of several pathologic conditions. Infiltrating cells derived from circulating monocytes contribute to tissue injury through the release of inflammatory cytokines and catecholamines. In particular, the present review will discuss the role of macrophages in heart failure, atherosclerosis, and anthracycline-dependent cardiotoxicity. Prolonged inflammatory response and increased apoptotic cell death sustained by chronic activation of the transcription factor NFκB are the basis of heart failure pathogenesis. Here, we will discuss the involvement of NFκB signaling in macrophage-dependent cardiac damage and its use as a therapeutic target in the treatment of cardiovascular pathologies.
Full article
Figure 1
Open AccessArticle
Assessing the Impact of Melanin Content on the Reliability of the Idylla™ BRAF Mutation Test
J. Mol. Pathol. 2023, 4(4), 307-317; https://doi.org/10.3390/jmp4040025 - 29 Nov 2023
Abstract
►▼
Show Figures
Aims: This study aims to investigate the potential influence of melanin content on the performance of the Idylla™ BRAF Mutation Test. Specifically, we assess whether melanin levels in samples impact the test’s reliability, thereby validating its clinical utility in accelerating melanoma diagnosis and
[...] Read more.
Aims: This study aims to investigate the potential influence of melanin content on the performance of the Idylla™ BRAF Mutation Test. Specifically, we assess whether melanin levels in samples impact the test’s reliability, thereby validating its clinical utility in accelerating melanoma diagnosis and potentially improving patient prognosis. Methods: We conducted a retrospective analysis of 98 confirmed melanoma samples collected between February 2020 and November 2020. Formalin-fixed paraffin-embedded (FFPE) slides were evaluated by two independent observers using light microscopy to categorise samples into three groups based on melanin content (no, low, or high) following a standardised system. The samples underwent the Idylla™ BRAF Mutation Test and were compared with results obtained from next-generation sequencing (NGS). Results: Quantification cycle (Cq) values were utilised to assess for interference from melanin levels on the Idylla™ BRAF Mutation Test results. Statistical analyses revealed no significant differences in Cq values based on melanin content categories. Furthermore, analysis of polymerase chain reaction PCR curves did not indicate any notable influence of melanin. Discordant results with NGS are discussed. Conclusions: The study demonstrates that melanin content in samples does not significantly affect the performance of the Idylla™ BRAF Mutation Test. These results provide robust evidence supporting the confident application of the test in clinical settings, even for samples with high melanin content. The ability to obtain rapid on-site results holds promising potential in guiding timely and appropriate treatment decisions, thereby contributing to improved patient prognosis. What is already known on this topic—Prior research conducted by Petty et al. (2020) including 23 melanoma samples suggested that melanin does not significantly interfere with the Idylla™ BRAF Mutation Test by stating they were concordant with reference laboratory testing. What this study adds—This current study builds upon prior research with a larger sample size of 98. In addition to examining concordance between the Idylla™ BRAF Mutation Test and next generation sequencing, this study examines PCR curves and effect on Cq values, providing more robust evidence that melanin content in FFPE samples does not have a significant impact on the accuracy of the Idylla™ BRAF Mutation Test. How this study might affect research, practice or policy—The additional evidence base provided by this study is valuable for researchers, clinicians, and policymakers, as it supports the integration of the Idylla™ BRAF Mutation Test as a rapid and accurate method for detecting these mutations in melanoma patients.
Full article
Figure 1
Open AccessReview
STING-Associated Vasculopathy with Onset in Infancy: A Review Focusing on Pathophysiology and Treatment Options
J. Mol. Pathol. 2023, 4(4), 294-306; https://doi.org/10.3390/jmp4040024 - 13 Nov 2023
Abstract
STING-associated vasculopathy with onset in infancy (SAVI) is a rare type Ι interferonopathy caused by gain of function mutations in an encoding stimulator of interferon genes (STING) protein 1. SAVI is characterized by neonatal or infantile-onset systemic inflammation, mainly affecting peripheral cutaneous blood
[...] Read more.
STING-associated vasculopathy with onset in infancy (SAVI) is a rare type Ι interferonopathy caused by gain of function mutations in an encoding stimulator of interferon genes (STING) protein 1. SAVI is characterized by neonatal or infantile-onset systemic inflammation, mainly affecting peripheral cutaneous blood vessels, skin, and lungs. The main disease manifestations include recurrent febrile episodes, cough, dyspnea, and failure to thrive, in association with progressive interstitial lung disease, polyarthritis, and cold-induced red violet plaques or papules on fingers, knees, toes, heels, nasal tip, and ears that can lead to distal ulcerations, skin necrosis, tissue loss, and autoamputation. For the management of SAVI, JAK inhibitors can be a valuable therapeutic intervention that hampers disease progression, while conventional immunosuppressive treatments have shown minimal efficacy. This review aims to describe the underlying pathophysiologic mechanisms of SAVI, highlighting the main clinical manifestations and discussing the current treatment approaches.
Full article
(This article belongs to the Collection Feature Papers in Journal of Molecular Pathology)
►▼
Show Figures
Figure 1
Open AccessReview
Mitochondrial Dynamics in Ovarian Cancer: Pathophysiology and Therapeutic Implications
J. Mol. Pathol. 2023, 4(4), 275-293; https://doi.org/10.3390/jmp4040023 - 06 Nov 2023
Abstract
►▼
Show Figures
Background: Ovarian cancer is often characterized by aggressive growth and chemoresistance, leading to a poor prognosis. The energy and nutrient acquisition through metabolic reprogramming has been reported to facilitate cancer cell proliferation, invasion, and metastasis. Therefore, a therapeutic strategy to consider is to
[...] Read more.
Background: Ovarian cancer is often characterized by aggressive growth and chemoresistance, leading to a poor prognosis. The energy and nutrient acquisition through metabolic reprogramming has been reported to facilitate cancer cell proliferation, invasion, and metastasis. Therefore, a therapeutic strategy to consider is to rewire energy metabolism. Mitochondrial dynamics have a profound impact on the metabolic profiles. In this review, we summarize the current understanding of the molecular mechanisms governing mitochondrial dynamics and their impact on cell proliferation and invasion and discuss future perspectives for therapeutic strategies and research directions. Methods: A search was conducted for literature published up to 30 June 2023 using the online databases PubMed and Google Scholar in this narrative literature review. Results: Mitochondria are essential for regulating metabolic reprogramming to meet the increasing energy demand for rapid cancer cell proliferation and invasion. A metabolic switch from OXPHOS to glycolysis may promote invasion, and OXPHOS-driven metabolism may be associated with proliferation, chemoresistance, and stemness. Many ovarian cancer cells are known to favor glycolysis over OXPHOS, but the opposite takes place in the subpopulation of cancer cells. The preference for glycolysis versus OXPHOS in ovarian cancer cells may be determined by histopathologic types, the unique genetic profile of energy metabolism, and intrinsic (e.g., oncogenic signaling) and extrinsic (e.g., nutritional status and hypoxia) factors. Conclusions: Preclinical studies suggest that mitochondrial dynamics regulators have therapeutic potential in ovarian cancer, but some factors limit their beneficial effects.
Full article
Figure 1
Open AccessBrief Report
Technical Validation of a Fully Integrated NGS Platform in the Real-World Practice of Italian Referral Institutions
by
, , , , , , , , , , , , and
J. Mol. Pathol. 2023, 4(4), 259-274; https://doi.org/10.3390/jmp4040022 - 31 Oct 2023
Abstract
►▼
Show Figures
Aims: To date, precision medicine has played a pivotal role in the clinical administration of solid-tumor patients. In this scenario, a rapidly increasing number of predictive biomarkers have been approved in diagnostic practice or are currently being investigated in clinical trials. A pitfall
[...] Read more.
Aims: To date, precision medicine has played a pivotal role in the clinical administration of solid-tumor patients. In this scenario, a rapidly increasing number of predictive biomarkers have been approved in diagnostic practice or are currently being investigated in clinical trials. A pitfall in molecular testing is the diagnostic routine sample available to analyze predictive biomarkers; a scant tissue sample often represents the only diagnostical source of nucleic acids with which to conduct molecular analysis. At the sight of these critical issues, next-generation sequencing (NGS) platforms emerged as referral testing strategies for the molecular analysis of predictive biomarkers in routine practice, but the need for highly skilled personnel and extensive working time drastically impacts the widespread diffusion of this technology in diagnostic settings. Here, we technically validate a fully integrated NGS platform on diagnostic routine tissue samples previously tested with an NGS-based diagnostic workflow by a referral institution. Methods: A retrospective series of n = 64 samples (n = 32 DNA, n = 32 RNA samples), previously tested using a customized NGS assay (SiRe™ and SiRe fusion), was retrieved from the internal archive of the University of Naples Federico II. Each sample was tested by adopting an Oncomine Precision Assay (OPA), which is able to detect 2769 molecular actionable alterations [hotspot mutations, copy number variations (CNV) and gene fusions] on fully integrated NGS platforms (Genexus, Thermo Fisher Scientific (Waltham, MA, USA). The concordance rate between these technical approaches was determined. Results: The Genexus system successfully carried out molecular analysis in all instances. A concordance rate of 96.9% (31 out of 32) was observed between the OPA and SiRe™ panels both for DNA- and RNA-based analysis. A negative predictive value of 100% and a positive predictive value of 96.9% (62 out of 64) were assessed. Conclusions: A fully automatized Genexus system combined with OPA (Thermo Fisher Scientific) may be considered a technically valuable, time-saving sequencing platform to test predictive biomarkers in diagnostic routine practice.
Full article
Figure 1
Open AccessArticle
Mobilising Collaboration among Stakeholders to Optimise the Growing Potential of Data for Tackling Cancer
by
, , , , , , , , , , , , , , , , , , , , , , and add
Show full author list
remove
Hide full author list
J. Mol. Pathol. 2023, 4(4), 234-258; https://doi.org/10.3390/jmp4040021 - 27 Oct 2023
Abstract
Effective cancer diagnosis, treatment and control depend on interactions among numerous distinct factors, from technology to data to skills to sociology. But a crucial influence is the extent to which the health system takes account of the distinct perspectives of the many different
[...] Read more.
Effective cancer diagnosis, treatment and control depend on interactions among numerous distinct factors, from technology to data to skills to sociology. But a crucial influence is the extent to which the health system takes account of the distinct perspectives of the many different groups of interdependent stakeholders concerned with cancer, including patients, practitioners and planners. This paper provides some elucidation as to how far and how efficiently these interactions currently take place in Europe. It also makes some tentative suggestions as to how conscious systematic interventions could improve cancer outcomes. It is based on a series of expert panels and surveys conducted by the European Alliance for Personalised Medicine (EAPM) that provided information at the national level on three selected parameters: implementation of next-generation sequencing (NGS) and liquid biopsy (LB), attitudes of patients to prevention and practices of sharing genomic data among healthcare professionals (HCPs). The varying data infrastructure highlights the urgent need for substantial improvements to accommodate the increasing importance of genomics data in cancer diagnosis and care. Additionally, we identify disparities in age-specific approaches to cancer prevention, emphasising the necessity for tailored strategies to address unique age group perspectives. Moreover, distinct regional prioritizations in cancer treatment underscore the importance of considering regional variations when shaping future cancer care strategies. This study advocates for collaborative data sharing supported by technological innovation to overcome these challenges, ultimately fostering a holistic and equitable provision of cancer care in Europe.
Full article
(This article belongs to the Topic Novel Discoveries in Oncology)
►▼
Show Figures
Figure 1
Open AccessCase Report
Intraoperative Flow Cytometry Upon and Beyond the Cell Cycle: A Case Study of the Characterization of a Bone Metastasis
by
, , , , , , , and
J. Mol. Pathol. 2023, 4(4), 225-233; https://doi.org/10.3390/jmp4040020 - 25 Oct 2023
Abstract
►▼
Show Figures
The accurate assessment of malignancy and the precise characterization of cancer type are pivotal in guiding clinical decisions and ensuring optimal patient outcomes. The challenging task of identifying the primary site of carcinoma, especially during a surgical procedure, is not always possible and
[...] Read more.
The accurate assessment of malignancy and the precise characterization of cancer type are pivotal in guiding clinical decisions and ensuring optimal patient outcomes. The challenging task of identifying the primary site of carcinoma, especially during a surgical procedure, is not always possible and necessitates the exploration of novel, innovative diagnostic techniques. In this report, we detail a unique case of carcinoma of unknown primary origin encountered during an orthopedic surgical procedure. We introduce a novel intraoperative flow cytometry (iFC) methodology, distinctly different from traditional flow cytometry, which is tailored for real-time assessment during surgeries. This iFC technique, applied in a bone metastasis case of unknown primary origin, enabled DNA content analysis and the quantification of cytokeratin for rapid malignancy characterization, presenting an avenue for immediate surgical guidance and decision making. The case was distinctively characterized using iFC, shedding light on the potential of this emerging technique. iFC has been gaining traction because of its ability to facilitate cancer cell assessment and margin evaluation. It has been successfully applied across a wide spectrum of neoplastic conditions. Our innovative, two-step approach using iFC encompasses (1) DNA content analysis, which serves as a reliable indicator for the detection of cancer cells, and (2) the quantification of cytokeratin, a pivotal marker, which aids in the characterization and classification of a malignancy. In this case, the malignancy was classified as a carcinoma. The findings obtained from iFC were subsequently validated through pathology assessment, confirming the accuracy and reliability of our approach. This noteworthy case strengthens the potential of iFC as a novel tool in malignancy assessment, which is not just limited to cell cycle analysis but instead extends beyond this application. The promising results obtained from this case study serve as a testament to the need for more extensive research in clinical studies.
Full article
Figure 1
Open AccessSystematic Review
IL10 Gene and Neurodegenerative Sclerosis: A Systematic Review and Meta-Analysis
by
, , , and
J. Mol. Pathol. 2023, 4(4), 213-224; https://doi.org/10.3390/jmp4040019 - 29 Sep 2023
Abstract
Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are incurable degenerative scleroses with unclear etiology. Neuroinflammation is an important factor in the neurodegeneration characteristic of these diseases. Additionally, Interleukin 10 (IL10) can inhibit the synthesis of inflammatory cytokines and plays a protective role
[...] Read more.
Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are incurable degenerative scleroses with unclear etiology. Neuroinflammation is an important factor in the neurodegeneration characteristic of these diseases. Additionally, Interleukin 10 (IL10) can inhibit the synthesis of inflammatory cytokines and plays a protective role against neurodegeneration associated with neuroinflammation. Thus, we developed a systematic review and meta-analysis in order to clarify the relationship between polymorphisms in the IL10 gene and MS and/or ALS. We searched for observational studies in four international databases without time restrictions. Seventeen studies were added to the systematic review and six polymorphisms were observed: IL10-592 (rs1800872; C>A), IL10-819 (rs1800871; C>T), IL10-1082 (rs1800896; A>G), IL10-2763 (rs6693899; A>C), IL10-2849 (rs6703630; A>G) and IL10-3575 (rs1800890; A>T). In the meta-analysis, we used odds ratio (OR) and 95% confidence interval (CI) to evaluate the association of IL10-1082, IL10-819 and IL10-592 polymorphisms and MS. We found a positive association of MS with the IL10-1082 SNP in genotypic comparison (AG+GG vs. AA) (OR = 1.23; 95% CI = 1.01–1.51; p = 0.04). Our search did not find any article relating polymorphisms in the IL10 gene with ALS. Therefore, our analysis indicates a possible association of IL10 gene SNPs in the development and progression of MS.
Full article
(This article belongs to the Special Issue State-of-the-Art in Neuropathology)
►▼
Show Figures
Figure 1
Open AccessReview
The Potential Role of Histone Modifications in Glioblastoma Therapy: Review Article
J. Mol. Pathol. 2023, 4(4), 196-212; https://doi.org/10.3390/jmp4040018 - 25 Sep 2023
Abstract
Glioblastoma (GBM) is considered the most aggressive primary brain tumor. Recurrence after treatment is a significant problem with a failed response to optimal therapies. The recurrence of GBM is linked to different cellular and molecular pathways. Not only genetics are involved in gliomagenesis,
[...] Read more.
Glioblastoma (GBM) is considered the most aggressive primary brain tumor. Recurrence after treatment is a significant problem with a failed response to optimal therapies. The recurrence of GBM is linked to different cellular and molecular pathways. Not only genetics are involved in gliomagenesis, but also epigenetics. Histone modulation through acetylation, phosphorylation, ubiquitination, and methylation can regulate gene expression and may play a role in the pathogenesis of GBM. Preclinical and clinical studies currently target epigenetic enzymes in gliomas, including a new generation of histone deacetylase (HDAC) inhibitors. Herein, I tried to highlight current research in glioma epigenetics, focusing on the culprit of histone modifications and the use of HDAC target therapies as a possible treatment line for glioblastoma.
Full article
(This article belongs to the Collection Feature Papers in Journal of Molecular Pathology)
►▼
Show Figures
Figure 1
Open AccessStudy Protocol
Relationship between Burnout, Cardiovascular Risk Factors, and Inflammatory Markers: A Protocol for Scoping Review
by
, , , , , , , , and
J. Mol. Pathol. 2023, 4(3), 189-195; https://doi.org/10.3390/jmp4030017 - 04 Aug 2023
Abstract
Background: Burnout is increasingly being recognized as a contributory factor to the erosion of a positive psychological state. Studies have examined the relationship between burnout and various inflammatory markers such as IL-1, IL-6, and TNF-alpha. Burnout is also associated with increased systemic inflammation
[...] Read more.
Background: Burnout is increasingly being recognized as a contributory factor to the erosion of a positive psychological state. Studies have examined the relationship between burnout and various inflammatory markers such as IL-1, IL-6, and TNF-alpha. Burnout is also associated with increased systemic inflammation along a continuum of symptom severity. This protocol is for a scoping review looking at the link between burnout, inflammatory markers, and cardiovascular risks or diseases. Methods: This study will be based on the preferred reporting items for systematic reviews and meta-analyses guidelines/checklists and the report of the review will be based on the same guideline. The study seeks to address the following principal questions. (i) What are the relevant inflammatory biomarkers that mediate cardiovascular risk factors in burnout? (ii) How do inflammatory biomarkers mediate cardiovascular risk factors in burnout? The outputs obtained from the literature search will be deduplicated using the Rayyan software. Results: We would create table summaries of findings to inform a narrative synthesis of the evidence from the papers included. Conclusion: The review article would help to concisely synthesize the available evidence on the relationship between burnout, inflammatory markers, and cardiovascular diseases.
Full article
(This article belongs to the Topic Molecular and Cellular Mechanisms of Diseases: Heart Disease)
Open AccessArticle
Activating Transcription Factor 1 (ATF1) Immunohistochemical Marker Distinguishes HCCC from MEC
J. Mol. Pathol. 2023, 4(3), 178-188; https://doi.org/10.3390/jmp4030016 - 01 Aug 2023
Abstract
The study aimed to compare 15 cases of mucoepidermoid carcinoma (MEC) and 15 cases of hyalinizing clear cell carcinoma (HCCC) using immunohistochemical staining and molecular analysis. Thirty samples were examined, and markers, including p63, CK5/6, SOX10, CK7, ATF1, and FISH probes specific to
[...] Read more.
The study aimed to compare 15 cases of mucoepidermoid carcinoma (MEC) and 15 cases of hyalinizing clear cell carcinoma (HCCC) using immunohistochemical staining and molecular analysis. Thirty samples were examined, and markers, including p63, CK5/6, SOX10, CK7, ATF1, and FISH probes specific to EWSR1 and MAML2, were used. Clear cell differentiation was observed in all MEC cases to some extent, with clear cell MEC showing the most prominent findings. Clear cell features were also present in conventional MEC, oncocytic MEC, and Warthin-like MEC, although to a lesser extent. The majority of cases were classified as low-grade MECs. MAML2 rearrangement was detected in all cases (except cases 11 and 14), while EWSR1 rearrangement was observed in a single case of clear cell MEC. These findings helped identify distinct subtypes within the mucoepidermoid carcinoma spectrum. The study emphasized the importance of utilizing immunohistochemical profiles, histopathological features, and molecular analysis for accurate diagnosis and classification of salivary gland neoplasms. HCCC was also discussed, and ATF1 was proposed as a marker to distinguish HCCC from morphologically similar neoplasms. The study concluded that a comprehensive approach combining immunohistochemistry, histopathology, and clinical correlation is essential for accurate diagnosis and classification, considering the variable expression of markers and potential overlap with other tumor types.
Full article
(This article belongs to the Special Issue Oncogenic Pathways in Maxillofacial Neoplasms That Differ From Other Topographies: Implications for Therapeutic and Prognostic Outcomes)
►▼
Show Figures
Figure 1
Open AccessArticle
Distribution of HPV Types in Tumor Tissue from Non-Vaccinated Women with Cervical Cancer in Norway
J. Mol. Pathol. 2023, 4(3), 166-177; https://doi.org/10.3390/jmp4030015 - 28 Jul 2023
Abstract
►▼
Show Figures
Background: Understanding the distribution of HPV types in cervical cancer cases is crucial for evaluating the effectiveness of HPV screening and vaccination in reducing cervical cancer burden. This study aimed to assess genotype prevalence in the pre-vaccine era among 178 cervical cancer cases
[...] Read more.
Background: Understanding the distribution of HPV types in cervical cancer cases is crucial for evaluating the effectiveness of HPV screening and vaccination in reducing cervical cancer burden. This study aimed to assess genotype prevalence in the pre-vaccine era among 178 cervical cancer cases detected during a 20-year screening period in Northern Norway and compare the potential efficacy of HPV vaccines in preventing cervical cancer. Methods: A total of 181 formalin-fixed paraffin-embedded (FFPE) tissue samples from non-vaccinated women diagnosed with cervical cancer between 1995 and 2015 in Troms and Finnmark, Norway, were analyzed using a 45-type HPV DNA test. The results were compared to a 7-type HPV mRNA test targeting oncogenic types included in the nonavalent HPV vaccine. Results: Invalid HPV test results were observed in 1.7% (3/181) of the samples and were subsequently excluded from further analysis. Among the remaining cases, 92.7% (165/178) tested positive for HPV using any test combination. HPV DNA was detected in 159 cases (89.3%), while HPV mRNA was detected in 149 cases (83.7%). The most prevalent HPV types were 16 and 18, responsible for 70.8% of the cases, with the nonavalent vaccine types accounting for 86.6% of cases. HPV 35 was identified in eight cases (4.5%). Conclusion: The bivalent/quadrivalent HPV vaccines have the potential to prevent 76.4% (126/165) of HPV-positive cervical cancer cases, while the nonavalent vaccine could prevent 93.3% (154/165) of cases. Tailoring screening strategies to target HPV types with the highest oncogenic potential may improve cervical cancer detection and enable targeted interventions for high-risk individuals. The use of a 7-type HPV mRNA test holds promise as an advantageous approach.
Full article
Figure 1
Open AccessArticle
A Real-World Study Reporting the Use of Foundation Medicine® Testing in Portugal
by
and
J. Mol. Pathol. 2023, 4(3), 156-165; https://doi.org/10.3390/jmp4030014 - 20 Jul 2023
Abstract
►▼
Show Figures
Foundation Medicine® testing is a next-generation sequence (NGS)-based platform that allows clinicians to obtain the comprehensive genomic profiling (CGP) of several cancers. By using NGS approaches, relevant genomic alterations can be identified in a short timeframe, providing guidance to diagnostic and therapeutic
[...] Read more.
Foundation Medicine® testing is a next-generation sequence (NGS)-based platform that allows clinicians to obtain the comprehensive genomic profiling (CGP) of several cancers. By using NGS approaches, relevant genomic alterations can be identified in a short timeframe, providing guidance to diagnostic and therapeutic decisions. This study reports the implementation of three commercially available Foundation Medicine® tests in a Portuguese institution and explores the genomic alterations identified. Data obtained from 72 patients tested with Foundation Medicine® between July 2017 and December 2020 were analysed retrospectively. A total of 290 gene alterations were identified, and TP53 was the gene most frequently altered. Among the 67 successfully profiled samples, 37.3% presented a potentially actionable variation. Breast carcinoma represented the most frequent tumour-carrying variation that can be targeted using currently approved drugs. A limited number of potentially actionable variants using approved drugs was found in this study; however, the genomic information provided by Foundation Medicine® may help clinicians in directing cancer patients into clinical trials or to off-label treatments.
Full article
Figure 1
Open AccessReview
Liquid Biopsy in Advanced Colorectal Cancer: Clinical Applications of Different Analytes
by
, , , , , , , , and
J. Mol. Pathol. 2023, 4(3), 128-155; https://doi.org/10.3390/jmp4030013 - 05 Jul 2023
Abstract
Colorectal cancer is one of the most prevalent cancers nowadays. In the metastatic setting, diagnosis and treatment have relied on tumor tissue analysis. However, the different limitations of this approach have recently opened the door to the introduction of liquid biopsy in the
[...] Read more.
Colorectal cancer is one of the most prevalent cancers nowadays. In the metastatic setting, diagnosis and treatment have relied on tumor tissue analysis. However, the different limitations of this approach have recently opened the door to the introduction of liquid biopsy in the clinical setting. Liquid biopsy provides real-time information about the tumor and its heterogeneity in a simple, non-invasive, and repeatable way. There are several analytes that can be sought: exosomes, circulating tumor cells, and circulating tumor DNA, showing promising results in the areas of early detection, minimal residual disease, prognosis, or response to treatment. Here, we review the clinical applications of liquid biopsy in advanced colorectal cancer patients, focusing on metastatic diagnosis, prognostic assessment, drug sensitivity, treatment response, and acquired resistance monitoring.
Full article
(This article belongs to the Special Issue Liquid Biopsy in Solid Tumors)
►▼
Show Figures
Figure 1
Open AccessArticle
Analytical Validation and Clinical Utilization of the Oncomine Comprehensive Assay Plus Panel for Comprehensive Genomic Profiling in Solid Tumors
by
, , , , , , , , , and
J. Mol. Pathol. 2023, 4(2), 109-127; https://doi.org/10.3390/jmp4020012 - 07 Jun 2023
Cited by 1
Abstract
►▼
Show Figures
The detection of driver oncogenic variants and the recent identification of tumor-agnostic genomic biomarkers has driven the use of comprehensive genomic profiling (CGP) for disease diagnosis, prognosis, and treatment selection. The Oncomine™ Comprehensive Assay Plus (OCA+) panel uses DNA and RNA to detect
[...] Read more.
The detection of driver oncogenic variants and the recent identification of tumor-agnostic genomic biomarkers has driven the use of comprehensive genomic profiling (CGP) for disease diagnosis, prognosis, and treatment selection. The Oncomine™ Comprehensive Assay Plus (OCA+) panel uses DNA and RNA to detect single nucleotide variants (SNVs), small insertions/deletions (Indels), and structural variants (SVs) across 501 genes. Moreover, microsatellite instability (MSI), tumor mutational burden (TMB), and homologous recombination deficiency (HRD) status are assessed in a single workflow. Herein, we present the analytical validation and clinical utilization of OCA+. By using commercial reference materials, we found good analytical sensitivity, specificity, and precision for all biomarkers analyzed. The limit of detection (LoD) was validated for SNVs and Indels at 4%, except for Indels located in homopolymeric regions, where the LoD was 10%. An additional set of 81 tumor samples, including cytology smears, were sequenced to assess the clinical utility of the OCA+ across different tumor types. Among the clinical cohort, OCA+ demonstrated 100% accuracy, sensitivity, and specificity for all biomarkers analyzed, except for MSI assessment of endometrial cancer cases, where 83% accuracy and 67% sensitivity were achieved, compared to PCR and IHC. The validation of accuracy and robustness of this assay supports the OCA+’s utility for solid tumor CGP.
Full article
Figure 1
Open AccessReview
Different Subtypes of Osteosarcoma: Histopathological Patterns and Clinical Behaviour
J. Mol. Pathol. 2023, 4(2), 99-108; https://doi.org/10.3390/jmp4020011 - 16 May 2023
Cited by 1
Abstract
►▼
Show Figures
Osteosarcoma (OS) is a primary malignant bone tumour that usually occurs in children and adolescents. OS is a highly aggressive tumour type with a propensity for local invasion and systemic early metastasis to the lungs or other bones. According to the World Health
[...] Read more.
Osteosarcoma (OS) is a primary malignant bone tumour that usually occurs in children and adolescents. OS is a highly aggressive tumour type with a propensity for local invasion and systemic early metastasis to the lungs or other bones. According to the World Health Organization, there are different subtypes of OS, including conventional OS (osteoblastic, chondroblastic, fibroblastic), telangiectatic OS, low-grade OS, small-cell OS, parosteal OS, periosteal OS, and high-grade surface OS. In this mini review, we will discuss the background of OS and histopathological patterns and clinical behaviour of the disease. Understanding the subtypes of OS and their pathogenesis is crucial for developing more precise and effective therapies for OS patients.
Full article
Figure 1
Open AccessArticle
Sinonasal Hyalinizing Adenoid Cystic Carcinoma Is Molecularly Different from Its Salivary and Breast Counterparts
J. Mol. Pathol. 2023, 4(2), 89-98; https://doi.org/10.3390/jmp4020010 - 15 May 2023
Abstract
Adenoid cystic carcinoma (AdCC) is known to behave differently based on its location, histologic features, and molecular profile. Despite this understanding, efforts to use these molecular findings to develop personalized treatments have not yet been successful. The purpose of this retrospective study is
[...] Read more.
Adenoid cystic carcinoma (AdCC) is known to behave differently based on its location, histologic features, and molecular profile. Despite this understanding, efforts to use these molecular findings to develop personalized treatments have not yet been successful. The purpose of this retrospective study is to examine the molecular characteristics of AdCC with various histologic features in three different locations. A reference group of 20 classic cribriform AdCC cases from the parotid gland was included, along with 10 salivary AdCCs (Group 1), 10 sinonasal AdCCs with hyalinization (Group 2), and 10 solid mammary AdCCs with basaloid features (Group 3). Tissue samples were processed and tested using various molecular techniques, and the Wilcoxon signed-rank test was used to compare the different groups. Molecular data were obtained for both common and rare cases of sinonasal, salivary, and mammary AdCCs, revealing differences in molecular features depending on the tumor’s location. The molecular profile of the AdCCs in the experimental group varied depending on the site, with MYB gene rearrangements being common in all cases. We report the first MYB::KMT2C/D fusions in a subset of salivary AdCCs and sinonasal AdCCs but not in mammary adenoid cystic carcinoma with basaloid features. We conclude that co-occurring genetic alterations may vary among different sites and may have implications for the prognosis and treatment plan of AdCC. More research is needed to fully understand the mechanisms of KMT2C and KMT2D mutations in the development and progression of head and neck cancer, including their interactions with the NOTCH pathway.
Full article
(This article belongs to the Special Issue Oncogenic Pathways in Maxillofacial Neoplasms That Differ From Other Topographies: Implications for Therapeutic and Prognostic Outcomes)
►▼
Show Figures
Figure 1
Highly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Biomolecules, Cells, JMP, Pathogens, Viruses
Molecular and Cellular Mechanisms of Diseases: HIV
Topic Editors: Mara Biasin, Daria Lucia TrabattoniDeadline: 1 February 2024
Topic in
Biomedicines, CIMB, Endocrines, IJMS, JMP, Life, Reprod. Med.
Pathogenesis of Pregnancy-Related Complications 2.0
Topic Editors: Ilona Hromadnikova, Katerina KotlabovaDeadline: 31 August 2024
Topic in
Biomolecules, Cells, IJMS, JMP, Muscles
Molecular Mechanisms of Exercise and Healthspan
Topic Editors: Robert Wessells, Zhen YanDeadline: 2 November 2024
Topic in
Biomolecules, Cancers, Cells, IJMS, JCM, JMP, Organoids
Novel Discoveries in Oncology
Topic Editors: Alessia Filippone, Giovanna Casili, Marika Lanza, Michela CampoloDeadline: 30 November 2024
Conferences
Special Issues
Special Issue in
JMP
State-of-the-Art in Neuropathology
Guest Editors: Flavio Pisani, Valerio PisaniDeadline: 31 March 2024
Special Issue in
JMP
New Insights into Molecular Pathology of Brain Tumor
Guest Editor: Antonella ArcellaDeadline: 15 April 2024
Special Issue in
JMP
Liquid Biopsy in Solid Tumors
Guest Editors: Umberto Malapelle, Francesco PassigliaDeadline: 31 May 2024
Topical Collections
Topical Collection in
JMP
Feature Papers in Journal of Molecular Pathology
Collection Editors: Giancarlo Troncone, Pasquale Pisapia
Topical Collection in
JMP
Juggling the Various Facets of Modern Anatomic Pathology
Collection Editors: Pasquale Pisapia, Giancarlo Troncone