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J. Mol. Pathol., Volume 3, Issue 4 (December 2022) – 15 articles

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17 pages, 3929 KiB  
Review
Intertwining Neuropathogenic Impacts of Aberrant Circadian Rhythm and Impaired Neuroregenerative Plasticity in Huntington’s Disease: Neurotherapeutic Significance of Chemogenetics
by Sowbarnika Ravichandran, Ramalingam Suhasini, Sudhiksha Madheswaran Deepa, Divya Bharathi Selvaraj, Jemi Feiona Vergil Andrews, Viruthachalam Thiagarajan and Mahesh Kandasamy
J. Mol. Pathol. 2022, 3(4), 355-371; https://doi.org/10.3390/jmp3040030 - 09 Dec 2022
Viewed by 2293
Abstract
Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by abnormal progressive involuntary movements, cognitive deficits, sleep disturbances, and psychiatric symptoms. The onset and progression of the clinical symptoms have been linked to impaired adult neurogenesis in the brains of subjects with HD, [...] Read more.
Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by abnormal progressive involuntary movements, cognitive deficits, sleep disturbances, and psychiatric symptoms. The onset and progression of the clinical symptoms have been linked to impaired adult neurogenesis in the brains of subjects with HD, due to the reduced neurogenic potential of neural stem cells (NSCs). Among various pathogenic determinants, an altered clock pathway appears to induce the dysregulation of neurogenesis in neurodegenerative disorders. Notably, gamma-aminobutyric acid (GABA)-ergic neurons that express the vasoactive intestinal peptide (VIP) in the brain play a key role in the regulation of circadian rhythm and neuroplasticity. While an abnormal clock gene pathway has been associated with the inactivation of GABAergic VIP neurons, recent studies suggest the activation of this neuronal population in the brain positively contributes to neuroplasticity. Thus, the activation of GABAergic VIP neurons in the brain might help rectify the irregular circadian rhythm in HD. Chemogenetics refers to the incorporation of genetically engineered receptors or ion channels into a specific cell population followed by its activation using desired chemical ligands. The recent advancement of chemogenetic-based approaches represents a potential scientific tool to rectify the aberrant circadian clock pathways. Considering the facts, the defects in the circadian rhythm can be rectified by the activation of VIP-expressing GABAergic neurons using chemogenetics approaches. Thus, the chemogenetic-based rectification of an abnormal circadian rhythm may facilitate the neurogenic potentials of NSCs to restore the neuroregenerative plasticity in HD. Eventually, the increased neurogenesis in the brain can be expected to mitigate neuronal loss and functional deficits. Full article
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16 pages, 2468 KiB  
Article
DNA Mismatch Repair Proteins and BRAF V600E Detection by Immunohistochemistry in Colorectal Cancer Demonstrates Concordance with Next Generation Sequencing
by Joel Yambert, Leigh A. Henricksen, June Clements, Andrew Hannon, Alyssa Jordan, Shalini Singh, Katerina Dvorak, Colin C. Pritchard and Eric Q. Konnick
J. Mol. Pathol. 2022, 3(4), 339-354; https://doi.org/10.3390/jmp3040029 - 02 Dec 2022
Viewed by 2473
Abstract
Background and Aims: Multiple laboratory methods are used to screen patients with colorectal cancer (CRC) for mismatch repair (MMR) protein deficiency to identify possible Lynch syndrome patients. The goal of this study was to compare the agreement between ready-to-use immunohistochemistry (IHC) assays for [...] Read more.
Background and Aims: Multiple laboratory methods are used to screen patients with colorectal cancer (CRC) for mismatch repair (MMR) protein deficiency to identify possible Lynch syndrome patients. The goal of this study was to compare the agreement between ready-to-use immunohistochemistry (IHC) assays for MLH-1, PMS-2, MSH-2, MSH-6, and mutated BRAF at V600E and molecular methods in CRC cases. The inclusion of the BRAF V600E mutation testing is important for the identification of patients with sporadic CRC, as the BRAF V600E mutation is very rarely observed in patients with Lynch syndrome tumors. Methods: CRC cases were analyzed by ColoSeqTM tumor sequencing assay and VENTANA MMR IHC Panel that included anti-MLH1, anti-PMS2, anti-MSH2, anti-MSH6, and anti-BRAF V600E antibodies. Additionally, CRC cases with MLH1 IHC loss were evaluated for MLH1 promoter hypermethylation. Results: One hundred and eighteen cases were analyzed. The overall percent agreement (OPA) for each evaluated marker status compared to next-generation sequencing (NGS) exceeded 96%. Twenty-three cases were positive for the BRAF V600E mutation by IHC and NGS, and twenty cases showed loss of MLH1 protein and were positive for MLH1 hypermethylation. Samples with loss of MMR protein expression by IHC demonstrated genetic and/or epigenetic alterations that were consistent with the observed protein expression patterns. Conclusions: The results of this study indicate that ready-to-use IHC assays can correctly identify the loss of MMR proteins and the presence of mutated BRAF V600E protein, supporting the utility of the VENTANA MMR IHC Panel as an aid to stratify patients with sporadic CRC vs. potential Lynch syndrome. Full article
(This article belongs to the Topic Diagnostic Imaging and Pathology in Cancer Research)
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10 pages, 537 KiB  
Review
Optimal Assessment of Metastatic Breast Carcinoma: The Value of Cytopathology Combined with Molecular Analysis
by Ricella Souza da Silva and Fernando Schmitt
J. Mol. Pathol. 2022, 3(4), 329-338; https://doi.org/10.3390/jmp3040028 - 22 Nov 2022
Cited by 1 | Viewed by 1452
Abstract
Metastatic breast cancer (MBC) remains in most cases an incurable disease with genetic complexity and heterogeneity. Improvements in classification and management have been introduced, in addition to the development of endocrine and anti-HER2 targeted therapies. Currently, efforts are being made to delineate the [...] Read more.
Metastatic breast cancer (MBC) remains in most cases an incurable disease with genetic complexity and heterogeneity. Improvements in classification and management have been introduced, in addition to the development of endocrine and anti-HER2 targeted therapies. Currently, efforts are being made to delineate the best approach for the genomic landscape of MBC and, as result, molecular therapeutic targets. Here, we highlight the recent developments in the cytopathology of MBC, discussing cytological diagnostic approaches in the characterization of hallmarks, such as immunocytochemistry and genomic biomarkers. Cytological material can be processed for ancillary testing for diagnostic and therapeutic purposes. Reassessment of receptor status is indicated due to changes in tumor biology and metastatic presentation. PD-L1 expression is the only approved biomarker for predicting immune checkpoint inhibitor response in metastatic TNBC, evaluated by immunostaining. The feasibility of applying PD-L1 assays in MBC cytological samples can be recommended, with the adoption of a combined positive score. Non-formalin cytological samples provide higher purity, cellular yield, and better tumor fraction for single-multi gene assays. In MBC, molecular tests enable personalized therapy such as PIK3CA, NTRK fusion genes, and MSI. Cytopathology combined with molecular analysis must be performed effectively in routine clinical practice, through procedure standardization and experience dissemination. Full article
(This article belongs to the Special Issue The Cytopathology of Metastatic Breast Cancer)
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10 pages, 1757 KiB  
Article
The p16 Antagonist Gankyrin Is Overexpressed in Melanocytic Neoplasms
by Sara Moradi and Torsten Ehrig
J. Mol. Pathol. 2022, 3(4), 319-328; https://doi.org/10.3390/jmp3040027 - 21 Nov 2022
Viewed by 1447
Abstract
Gankyrin has a household function in essentially all cells by acting as a chaperone in the assembly of the 26S proteasome, but also functions as a tumor-promoting protein by antagonizing the tumor suppressors retinoblastoma protein, p16, and p53. While gankyrin is overexpressed in [...] Read more.
Gankyrin has a household function in essentially all cells by acting as a chaperone in the assembly of the 26S proteasome, but also functions as a tumor-promoting protein by antagonizing the tumor suppressors retinoblastoma protein, p16, and p53. While gankyrin is overexpressed in many neoplasms outside the skin, its expression in normal skin and cutaneous neoplasms has not been reported previously. We studied the expression of gankyrin in archival human formalin-fixed tissues of cutaneous neoplasms by immunohistochemistry with a monoclonal antibody, and found gankyrin to be overexpressed in 3 of 20 squamous cell carcinomas, none of 10 basal cell carcinomas, 13 of 18 melanocytic nevi, and 7 of 10 melanomas, in many cases with a predominantly nuclear location. Normal epidermal melanocytes expressed gankyrin to a lesser extent than neoplastic melanocytes. The overexpression in the in situ stage of squamous cell carcinoma and in melanocytic nevi suggests that gankyrin acts as a tumor-promoting protein in the early stages of the transition from normal to neoplastic cells. The frequent overexpression of gankyrin in melanocytic neoplasms is significant because it antagonizes the tumor suppressor, p16, which is strongly expressed in melanocytic nevi and some melanomas. Full article
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12 pages, 2503 KiB  
Commentary
RNA-Based Next-Generation Sequencing in the Somatic Molecular Testing of Non-Small-Cell Lung Cancer (NSCLC) in a Centralized Model: Real-World Data to Suggest It Is Time to Reconsider Testing Options
by Alison Finall
J. Mol. Pathol. 2022, 3(4), 307-318; https://doi.org/10.3390/jmp3040026 - 08 Nov 2022
Cited by 1 | Viewed by 2277
Abstract
Best practice in the management of non-squamous, non-small-cell lung cancer patients involves somatic testing for a range of molecular markers. Actionable oncogenic drivers of malignancy are increasingly being detected using RNA-based next-generation sequencing in the UK by referral to centralized genomic laboratory hubs. [...] Read more.
Best practice in the management of non-squamous, non-small-cell lung cancer patients involves somatic testing for a range of molecular markers. Actionable oncogenic drivers of malignancy are increasingly being detected using RNA-based next-generation sequencing in the UK by referral to centralized genomic laboratory hubs. Recent audit data from the author’s case work have demonstrated an RNA sequencing failure rate of 35%. This article examines the real-world context, which may account for this failure rate, and discusses alternative options for patient care pathways. Full article
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14 pages, 2302 KiB  
Review
Comprehensive Review of Metastatic Breast Carcinoma in Cytology Specimens
by Swikrity U. Baskota, Daniel Qazi, Ashish Chandra and Poonam Vohra
J. Mol. Pathol. 2022, 3(4), 293-306; https://doi.org/10.3390/jmp3040025 - 07 Nov 2022
Cited by 1 | Viewed by 4033
Abstract
Breast carcinomas are known to metastasize to various organs of the human body. Fine needle aspiration cytology or exfoliative cytology often are the standard method for diagnosis at these metastatic sites due to ease of procurement of diagnostic material, accessibility, less complications, high [...] Read more.
Breast carcinomas are known to metastasize to various organs of the human body. Fine needle aspiration cytology or exfoliative cytology often are the standard method for diagnosis at these metastatic sites due to ease of procurement of diagnostic material, accessibility, less complications, high sensitivity, and specificity of diagnosis and evaluation of biomarker status needed to guide future management. This comprehensive review article discusses in detail metastatic patterns, cytomorphology of metastatic breast cancer at different body sites, immunohistochemistry needed for diagnosis of breast carcinoma, sensitivity and specificity of diagnosis and breast biomarker assays in the cytology material. Full article
(This article belongs to the Special Issue The Cytopathology of Metastatic Breast Cancer)
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7 pages, 851 KiB  
Article
Langerhans Cell Histiocytosis-Associated Pulmonary Adenocarcinoma: A Word of Caution during Molecular Determinations
by Laura Melocchi, Michele Mondoni, Umberto Malapelle and Giulio Rossi
J. Mol. Pathol. 2022, 3(4), 286-292; https://doi.org/10.3390/jmp3040024 - 03 Nov 2022
Viewed by 1641
Abstract
Background: Smoking habit is a common cause of pulmonary Langerhans cell histiocytosis (PLCH) and lung cancer and both diseases may coexist in the lung and share genetic alterations, such as V600E BRAF mutations. We collected a small series of three cases of PLCH-associated [...] Read more.
Background: Smoking habit is a common cause of pulmonary Langerhans cell histiocytosis (PLCH) and lung cancer and both diseases may coexist in the lung and share genetic alterations, such as V600E BRAF mutations. We collected a small series of three cases of PLCH-associated lung adenocarcinoma in order to evaluate the molecular setup in both components and underline the critical role of careful tissue selection for predictive molecular driver testing. Methods: Three cases of PLCH-associated adenocarcinoma were collected from consultation files. Clinical data from referring physicians and clinical data were obtained. The surgical biopsies were tested by immunohistochemistry and molecular analysis after separate dissection of adenocarcinoma cells and Langerhans histiocytes. Results: There were three active smoking men with a median age at diagnosis of 60.6 years. PLCH was disclosed at imaging during work-up for suspected lung cancer. Molecular analysis revealed KRAS (G12C and G13C) mutations in two cases and V600E BRAF mutation in one case of PLCH. Immunostaining with the V600E BRAF mutation specific primary antibody VE1 correctly recognized BRAF-mutated LCH. One case was wild-type in both diseases. Two similar cases were found in the literature, one of which showed a discrepant KRAS (G12D) mutation in adenocarcinoma and a V600E BRAF mutation in LCH; Conclusions: This case series of PLCH-associated adenocarcinoma underline the possibility to disclose identical genetic alterations in co-existing benign and malignant pathologies, then potentially creating erroneous interpretation of molecular analysis leading to inadequate therapeutic options in case of incorrect diagnostic recognition and inappropriate selection of both components through microdissection. Full article
(This article belongs to the Special Issue Liquid Biopsy in Solid Tumors)
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13 pages, 7317 KiB  
Article
Adenosquamous Carcinomas and Mucinous Adenocarcinoma of the Minor Salivary Glands: Immunohistochemical and Molecular Insights
by Bacem Khalele, Juan B. Laforga, Karol Kajo and Katarína Kajová Macháleková
J. Mol. Pathol. 2022, 3(4), 273-285; https://doi.org/10.3390/jmp3040023 - 03 Nov 2022
Cited by 2 | Viewed by 1688
Abstract
There is confusion about the diagnosis, histogenesis and taxonomical efforts regarding adenosquamous carcinomas (ASCs) and mucinous adenocarcinomas (MACs), especially with calls for reconsidering the nature of high-grade mucoepidermoid carcinoma (MEC). This study aims to compare the genetic profiles of ASCs and MACs that [...] Read more.
There is confusion about the diagnosis, histogenesis and taxonomical efforts regarding adenosquamous carcinomas (ASCs) and mucinous adenocarcinomas (MACs), especially with calls for reconsidering the nature of high-grade mucoepidermoid carcinoma (MEC). This study aims to compare the genetic profiles of ASCs and MACs that have been previously reported in the literature and investigate if either ASC or MAC is closer in genetic mutations to high-grade MEC. Systematic searches in the NCBI, Web of Science, and Scopus databases were performed between January 2000 and August 2022. The retrieved genetic mutations were processed and annotated. Protein–protein network analysis was conducted for each neoplasm. The results were viewed and discussed in terms of molecular oncogenesis of ASCs and MACs at different topographies. Molecular profile mapping was conducted by annotating all the retrieved genes for each neoplasm using genetic network analysis (Cystoscape software program). The genetic profile of each lesion was compared to that of high-grade MEC. To conclude, both genetic profiles do not tend to intersect specifically with high-grade MEC, except for the generic mutations commonly detected in all high-grade head and neck tumors. However, the availability of data on the molecular profile of each lesion limits the generalizability of the findings of this study. Full article
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11 pages, 1478 KiB  
Project Report
The Implementation of Laboratory Information Management System in Multi-Site Genetics Study in Africa: The Challenges and Up-Scaling Opportunities
by Oluwafemi Gabriel Oluwole, Chandre Oosterwyk, Dominique Anderson, Samuel Mawuli Adadey, Khuthala Mnika, Noluthando Manyisa, Abdoulaye Yalcouye, Edmond T. Wonkam, Elvis Twumasi Aboagye, Yacouba Dia, Esther Uwibambe, Mario Jonas, Roy Priestley, Kalinka Popel, Thumeka Manyashe, Carmen de Cock, Victoria Nembaware and Ambroise Wonkam
J. Mol. Pathol. 2022, 3(4), 262-272; https://doi.org/10.3390/jmp3040022 - 22 Oct 2022
Cited by 2 | Viewed by 3054
Abstract
This study describes the roles of laboratory information management systems (LIMS) in multi-site genetics studies in Africa. We used the HiGeneS Africa project as a case study. The study participants were recruited in six African countries between 2019 to 2021. The Baobab LIMS, [...] Read more.
This study describes the roles of laboratory information management systems (LIMS) in multi-site genetics studies in Africa. We used the HiGeneS Africa project as a case study. The study participants were recruited in six African countries between 2019 to 2021. The Baobab LIMS, a server–client-based system (an African-led innovation) was used for the coordination of the biospecimen. The development phase of the LIMS showcased the team formation, data collection, biospecimen collection, and shipment strategies. The implementation phase showcased the biospecimen registration, processing, and quality control (QC) analytics. The sample QC was done using Nanodrop, Qubit, and PicoGreen/gDNATapestation assays. The results showed that a total of 3144 study participants were recruited from Cameroon, Ghana, Mali, Rwanda, Senegal, and South Africa. The biospecimen registration provided a comprehensive registry that included patient demographics, genetic information, and clinical and blood/saliva samples from the proband and family relatives. The QC analyzes identified 30 samples that failed QC, linked to overdue storage in the freezer before DNA extraction. The LIMS components implemented in this project formed a structure that can be upscaled to artificial intelligence-based LIMS. In conclusion, this study represents the largest and the most diverse collection of biospecimens for the genetic study of hearing impairment in Africa to date. A well-characterized LIMS should be recommended for multi-site molecular studies, particularly in Africa, to enhance African participation in global genomic medicine. Full article
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19 pages, 1657 KiB  
Review
The Roles of Calcium Ions in Parkinson’s Disease: Calcium Channel Inhibitors as a Novel Agents?
by Md Reyaz Alam, Khadga Raj and Shamsher Singh
J. Mol. Pathol. 2022, 3(4), 243-261; https://doi.org/10.3390/jmp3040021 - 19 Oct 2022
Cited by 2 | Viewed by 4284
Abstract
Parkinson’s disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons, which results in motor impairment. The rationale and objective of the review article is to determine whether CCBs use contributes to a lower risk of developing a first-time [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons, which results in motor impairment. The rationale and objective of the review article is to determine whether CCBs use contributes to a lower risk of developing a first-time diagnosis of PD. Ca2+ homeostasis disruption and mitochondrial dysfunction play a vital role in PD aetiology. In addition, the L-type voltage-gated calcium channel is expressed at high levels amongst nigral neurons, and could play a role in the pathogenesis of PD. In the dopaminergic neurons, Ca2+ entry through plasma membrane Cav1 channels drives a sustained feed-forward stimulation of mitochondrial oxidative phosphorylation. This study investigates the therapeutic potential of R- and T-type Ca2+ channel inhibition in light of new preclinical and clinical data and the feasibility of available Ca2+ channel blockers to cure PD progression. The R-type calcium channel is a type of voltage-dependent calcium channel. Available findings suggest that calcium homeostasis in dopaminergic neurons might be a valuable target for developing new drugs for PD patients. The limitations of our study include reports of observational studies with different follow-up periods. The specific roles of individual drugs and doses were also not mentioned because of nonreporting in the studies. Full article
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15 pages, 18353 KiB  
Review
The Value of Fine Needle Aspiration Biopsy in the Pre-Operative Assessment of the Axilla in Breast Cancer Patients
by Wendy A. Raymond and Pakan Kleinig
J. Mol. Pathol. 2022, 3(4), 228-242; https://doi.org/10.3390/jmp3040020 - 18 Oct 2022
Viewed by 3083
Abstract
This paper reviews the role of fine needle aspiration biopsy (FNAB) in assessing the axilla prior to definitive surgery or neoadjuvant therapy in breast cancer patients. The radiological criteria for biopsy are discussed and pathological techniques and pitfalls illustrated. The sensitivity and specificity [...] Read more.
This paper reviews the role of fine needle aspiration biopsy (FNAB) in assessing the axilla prior to definitive surgery or neoadjuvant therapy in breast cancer patients. The radiological criteria for biopsy are discussed and pathological techniques and pitfalls illustrated. The sensitivity and specificity of the technique and the clinical utility are addressed, with particular reference to the current controversies in the management of the axilla in the light of the American College of Surgeons Oncology Group Z0011 trial results. The low morbidity procedure of FNAB is recommended when the radiological and clinical features suggest a high yield from the abnormal axillary nodes, with consideration of core biopsy if an expected positive result is not obtained or the circumstances require tissue for ancillary studies. In conclusion, FNAB of the axilla is a highly sensitive procedure which can offer further valuable information to assist in clinical decision making. The technique is of particular value in the setting of a large primary tumour size and multiple enlarged nodes. A summary flow chart is provided to facilitate pre-operative management of the axilla and to encourage a universal approach. Full article
(This article belongs to the Special Issue The Cytopathology of Metastatic Breast Cancer)
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9 pages, 2666 KiB  
Article
Comparison of GATA3, GCDFP15, Mammaglobin and SOX10 Immunocytochemistry in Aspirates of Metastatic Breast Cancer
by Joshua J. X. Li, Joanna K. M. Ng, Conrad H. C. Lee, Cheuk-Yin Tang, Julia Y. S. Tsang and Gary M. Tse
J. Mol. Pathol. 2022, 3(4), 219-227; https://doi.org/10.3390/jmp3040019 - 13 Oct 2022
Cited by 2 | Viewed by 1695
Abstract
Introduction: Metastatic cancers are frequently detected on fine-needle aspiration (FNA) cytology, and confirmation of metastatic breast cancer often requires immunocytochemistry. Tissue provisioning for FNA specimens is important. In this study, GATA3, gross cystic disease fluid protein-15 (GCDFP15), mammaglobin (MMG), and SOX10 were performed [...] Read more.
Introduction: Metastatic cancers are frequently detected on fine-needle aspiration (FNA) cytology, and confirmation of metastatic breast cancer often requires immunocytochemistry. Tissue provisioning for FNA specimens is important. In this study, GATA3, gross cystic disease fluid protein-15 (GCDFP15), mammaglobin (MMG), and SOX10 were performed on cell block preparations from aspirates of histologically confirmed metastatic breast cancers. The diagnostic performance of single markers and combinations of these markers were investigated with the aim to construct a tissue-efficient immunopanel. Methodology: Aspirates of metastatic breast cancer with corresponding histology and biomarker (estrogen receptor (ER), progesterone receptor (PR), HER2 and ki67) profile were retrieved. ER, GATA3, GCDFP15, MMG and SOX10 immunostains were performed on cell block sections and their expressions were assessed and compared. Results: Immunostaining was performed on a total of 115 aspirates. GATA3 showed the highest expression, followed by MMG, GCDFP15 and SOX10. Twenty-three, five and five cases expressed GATA3, MMG and SOX10 only. The five cases expressing SOX10 only were ER negative, and SOX10 expression was negatively associated with ER (p = 0.001), MMG (p = 0.001), GCDFP15 (p = 0.010) and GATA3 (p = 0.002), whereas GATA3 expression showed positive correlation with ER positivity (p < 0.001). MMG and GCDFP15 showed association with high Ki67 (p < 0.05), and no correlations were found with HER2 expression. Conclusion: In this cohort, GATA3 was the most sensitive single marker. The addition of MMG and SOX10 increases the sensitivity for detection of ER positive and ER negative breast cancers, respectively. These findings support the use of a combination of GATA3/MMG/SOX10 for confirmation of metastatic breast cancer. Full article
(This article belongs to the Special Issue The Cytopathology of Metastatic Breast Cancer)
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18 pages, 1000 KiB  
Review
The Comparison of Mutational Progression in SARS-CoV-2: A Short Updated Overview
by Abeer Asif, Iqra Ilyas, Mohammad Abdullah, Sadaf Sarfraz, Muhammad Mustafa and Arif Mahmood
J. Mol. Pathol. 2022, 3(4), 201-218; https://doi.org/10.3390/jmp3040018 - 06 Oct 2022
Cited by 11 | Viewed by 2429
Abstract
The COVID-19 pandemic has impacted the world population adversely, posing a threat to human health. In the past few years, various strains of SARS-CoV-2, each with different mutations in its structure, have impacted human health in negative ways. The severe acute respiratory syndrome [...] Read more.
The COVID-19 pandemic has impacted the world population adversely, posing a threat to human health. In the past few years, various strains of SARS-CoV-2, each with different mutations in its structure, have impacted human health in negative ways. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations influence the virulence, antibody evasion, and Angiotensin-converting enzyme 2 (ACE2) affinity of the virus. These mutations are essential to understanding how a new strain of SARS-CoV-2 has changed and its possible effects on the human body. This review provides an insight into the spike mutations of SARS-CoV-2 variants. As the current scientific data offer a scattered outlook on the various type of mutations, we aimed to categorize the mutations of Beta (B.1.351), Gamma (P.1), Delta (B.1.612.2), and Omicron (B.1.1.529) systematically according to their location in the subunit 1 (S1) and subunit 2 (S2) domains and summarized their consequences as a result. We also compared the miscellany of mutations that have emerged in all four variants to date. The comparison shows that mutations such as D614G and N501Y have emerged in all four variants of concern and that all four variants have multiple mutations within the N-terminal domain (NTD), as in the case of the Delta variant. Other mutations are scattered in the receptor binding domain (RBD) and subdomain 2 (SD2) of the S1 domain. Mutations in RBD or NTD are often associated with antibody evasion. Few mutations lie in the S2 domain in the Beta, Gamma, and Delta variants. However, in the Omicron variant many mutations occupy the S2 domain, hinting towards a much more evasive virus. Full article
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5 pages, 198 KiB  
Article
EGFR Mutation in Nasopharyngeal Carcinoma
by Evren Uzun and Suna Erkilic
J. Mol. Pathol. 2022, 3(4), 196-200; https://doi.org/10.3390/jmp3040017 - 01 Oct 2022
Viewed by 1551
Abstract
Nasopharyngeal carcinoma is a malignant tumor of the nasopharynx. However, while radiotherapy is the primary choice of treatment, the treatment may fail due to distant metastasis in most patients at an advanced stage. Treatment agents against some mutations have led to the development [...] Read more.
Nasopharyngeal carcinoma is a malignant tumor of the nasopharynx. However, while radiotherapy is the primary choice of treatment, the treatment may fail due to distant metastasis in most patients at an advanced stage. Treatment agents against some mutations have led to the development of personalized treatment regimens. EGFR is one of the most studied molecules and has played a role in the development of a large number of cancer types. We aimed to demonstrate the EGFR mutation status in nasopharyngeal carcinomas. Twenty-six nasopharyngeal carcinomas were included in the study. EGFR mutation analysis was applied to the cases by the real-time PCR method. The results were evaluated statistically. No EGFR mutation was detected in any of the cases. Although EGFR expression is frequently shown in nasopharyngeal carcinomas immunohistochemically, the same positivity was not shown in genetic analysis. This result shows that the use of anti-EGFR agents in nasopharyngeal carcinoma treatment will not be effective. Full article
6 pages, 792 KiB  
Article
CD64 Staining in Dermatofibroma: A Sensitive Marker Raising the Question of the Cell Differentiation Lineage of This Neoplasm
by Mar Llamas-Velasco, Thomas Mentzel, Enrique Ovejero-Merino, María Teresa Fernández-Figueras and Heinz Kutzner
J. Mol. Pathol. 2022, 3(4), 190-195; https://doi.org/10.3390/jmp3040016 - 24 Sep 2022
Cited by 1 | Viewed by 1424
Abstract
Dermatofibroma (DF) is a mesenchymal tumor of the dermis, but its exact differentiation lineage is still uncertain. A progenitor cell that may be able to differentiate into fibroblastic, myofibroblastic, or fibrohistiocytic cells has been hypothesized. Some authors have also proposed the possibility of [...] Read more.
Dermatofibroma (DF) is a mesenchymal tumor of the dermis, but its exact differentiation lineage is still uncertain. A progenitor cell that may be able to differentiate into fibroblastic, myofibroblastic, or fibrohistiocytic cells has been hypothesized. Some authors have also proposed the possibility of a monocytic-histiocytic origin. We stained 47 consecutive dermatofibromas with CD64, CD34, CD14, CD163, and CD68 to test which marker is more reliable for the diagnosis and to gain insight into their histogenesis. From the 35 cases stained with the whole immunohistochemical panel, all were positive for CD64, mostly showing a strong and diffuse pattern. Regarding all the other staining, CD14 was strongly positive in 77% of the lesions and CD163 in 20%. The CD68 stain was intense and diffuse only in 20% of the cases. All lesions were negative for CD34, but two of them showed patchy and weak staining. DFs were immunohistochemically stained positively with a set of macrophage/monocyte/histiocyte lineage markers such as CD14, CD68, CD163, and CD64. This finding favors an active pro-inflammatory immature monocyte-lineage cell as the more suitable origin for DF. CD64 seems to be more sensitive than other markers to confirm the diagnosis. Full article
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