Laura Melocchi, M. Mondoni, U. Malapelle, G. Rossi
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.
{"title":"Langerhans Cell Histiocytosis-Associated Pulmonary Adenocarcinoma: A Word of Caution during Molecular Determinations","authors":"Laura Melocchi, M. Mondoni, U. Malapelle, G. Rossi","doi":"10.3390/jmp3040024","DOIUrl":"https://doi.org/10.3390/jmp3040024","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114521152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Khalele, J. Laforga, K. Kajo, Katarína Kajová Macháleková
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.
关于腺鳞状癌(ASCs)和粘液腺癌(MACs)的诊断、组织发生和分类学研究存在混淆，特别是要求重新考虑高级别粘液表皮样癌(MEC)的性质。本研究旨在比较先前文献中报道的ASC和MAC的遗传谱，并研究ASC或MAC在基因突变上是否更接近高级别MEC。在2000年1月至2022年8月期间对NCBI、Web of Science和Scopus数据库进行了系统检索。对检索到的基因突变进行处理和注释。对每个肿瘤进行蛋白-蛋白网络分析。从不同地形的ASCs和MACs的分子癌变角度对结果进行了观察和讨论。利用遗传网络分析(Cystoscape软件程序)对每个肿瘤的所有检索基因进行注释，从而进行分子图谱定位。将每个病变的遗传谱与高级别MEC的遗传谱进行比较。综上所述，除了在所有高级别头颈部肿瘤中常见的通用突变外，这两种基因图谱并不倾向于与高级别MEC特异性相交。然而，每个病变的分子谱数据的可用性限制了本研究结果的普遍性。
{"title":"Adenosquamous Carcinomas and Mucinous Adenocarcinoma of the Minor Salivary Glands: Immunohistochemical and Molecular Insights","authors":"B. Khalele, J. Laforga, K. Kajo, Katarína Kajová Macháleková","doi":"10.3390/jmp3040023","DOIUrl":"https://doi.org/10.3390/jmp3040023","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128802737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. Oluwole, C. Oosterwyk, Dominique Anderson, S. M. Adadey, K. Mnika, Noluthando Manyisa, A. Yalcouyé, Edmond T. Wonkam, Elvis Twumasi Aboagye, Y. Dia, Esther Uwibambe, Mario Jonas, Roy Priestley, Kalinka Popel, Thumeka Manyashe, Carmen de Cock, V. Nembaware, A. Wonkam
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.
{"title":"The Implementation of Laboratory Information Management System in Multi-Site Genetics Study in Africa: The Challenges and Up-Scaling Opportunities","authors":"O. Oluwole, C. Oosterwyk, Dominique Anderson, S. M. Adadey, K. Mnika, Noluthando Manyisa, A. Yalcouyé, Edmond T. Wonkam, Elvis Twumasi Aboagye, Y. Dia, Esther Uwibambe, Mario Jonas, Roy Priestley, Kalinka Popel, Thumeka Manyashe, Carmen de Cock, V. Nembaware, A. Wonkam","doi":"10.3390/jmp3040022","DOIUrl":"https://doi.org/10.3390/jmp3040022","url":null,"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, 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131678856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"The Roles of Calcium Ions in Parkinson’s Disease: Calcium Channel Inhibitors as a Novel Agents?","authors":"Md Reyaz Alam, Khadga Raj, Shamsher Singh","doi":"10.3390/jmp3040021","DOIUrl":"https://doi.org/10.3390/jmp3040021","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"254 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124193251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"The Value of Fine Needle Aspiration Biopsy in the Pre-Operative Assessment of the Axilla in Breast Cancer Patients","authors":"W. Raymond, Pakan Kleinig","doi":"10.3390/jmp3040020","DOIUrl":"https://doi.org/10.3390/jmp3040020","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"41 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130775376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Li, J. Ng, C. Lee, Cheuk-Yin Tang, J. Tsang, G. Tse
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.
{"title":"Comparison of GATA3, GCDFP15, Mammaglobin and SOX10 Immunocytochemistry in Aspirates of Metastatic Breast Cancer","authors":"J. Li, J. Ng, C. Lee, Cheuk-Yin Tang, J. Tsang, G. Tse","doi":"10.3390/jmp3040019","DOIUrl":"https://doi.org/10.3390/jmp3040019","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115877275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abeer Asif, I. Ilyas, M. Abdullah, S. Sarfraz, Muhammad Mustafa, Arif Mahmood
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.
{"title":"The Comparison of Mutational Progression in SARS-CoV-2: A Short Updated Overview","authors":"Abeer Asif, I. Ilyas, M. Abdullah, S. Sarfraz, Muhammad Mustafa, Arif Mahmood","doi":"10.3390/jmp3040018","DOIUrl":"https://doi.org/10.3390/jmp3040018","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131998876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"EGFR Mutation in Nasopharyngeal Carcinoma","authors":"Evren Uzun, S. Erkilic","doi":"10.3390/jmp3040017","DOIUrl":"https://doi.org/10.3390/jmp3040017","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129055504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Llamas‐Velasco, T. Mentzel, Enrique Ovejero-Merino, M. Fernández-Figueras, H. Kutzner
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.
{"title":"CD64 Staining in Dermatofibroma: A Sensitive Marker Raising the Question of the Cell Differentiation Lineage of This Neoplasm","authors":"M. Llamas‐Velasco, T. Mentzel, Enrique Ovejero-Merino, M. Fernández-Figueras, H. Kutzner","doi":"10.3390/jmp3040016","DOIUrl":"https://doi.org/10.3390/jmp3040016","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125149893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Periodontitis is a chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. Its high prevalence and negative effects on quality of life make it one of the current problems in dentistry. Porphyromonas gingivalis (P. gingivalis) is the predominant periodontal pathogen that expresses a number of virulence factors involved in the pathogenesis of periodontitis. P. gingivalis fimbriae are a critical factor in the interaction between the organism and the host tissue. They promote both bacterial adhesion and invasion into the target sites. Fimbriae are capable of binding to human saliva components, extracellular matrix proteins, and commensal bacteria, as well as firmly binding to the cellular integrin α5β1. After attachment to α5β1-integrin, P. gingivalis is captured by cellular pseudopodia, which makes invagination through an actin-mediated pathway possible. It has been proven that the invagination event also requires the participation of the host cell dynamin, actin fibers, microtubules and lipid rafts. Work has emerged investigating mutations in the proline-rich terminal domain (PRD) and their impact on disease development. Salivary antimicrobial peptides are early protective factors against microbial attack. Of great interest is fibronectin (FN) as the main competitor of P. gingivalis fimbriae. The FN can interact with cells in three different regions: the central cell-binding domain (CCBD), the COOH terminal heparin-binding domain (Hep2), and the type III connecting segment (IIICS), including the CS1 region (Yamada, 1991). CCBD is the major cell-adhesion domain of FN and contains an Arg–Gly–Asp (RGD) motif that is recognized by members of the cell adhesion receptor integrin family, including a5b1, which is the primary FN receptor in many cell types. The work focuses on identifying the relationship between the development of periodontitis and the presence of mutations in the adhesion domains of salivary proteins such as cellular fibronectin (cFN) and dynamin-2 (DYNM2).
{"title":"The Relationship between Mutations in Gene-Specific Domains of Salivary Fibronectin (cFn) and Dynamin-2 (Dynm-2) and the Development of Porphyromonas gingivalis-Initiated Periodontitis","authors":"E. Oleinik, A. Goncharenko","doi":"10.3390/jmp3030015","DOIUrl":"https://doi.org/10.3390/jmp3030015","url":null,"abstract":"Periodontitis is a chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. Its high prevalence and negative effects on quality of life make it one of the current problems in dentistry. Porphyromonas gingivalis (P. gingivalis) is the predominant periodontal pathogen that expresses a number of virulence factors involved in the pathogenesis of periodontitis. P. gingivalis fimbriae are a critical factor in the interaction between the organism and the host tissue. They promote both bacterial adhesion and invasion into the target sites. Fimbriae are capable of binding to human saliva components, extracellular matrix proteins, and commensal bacteria, as well as firmly binding to the cellular integrin α5β1. After attachment to α5β1-integrin, P. gingivalis is captured by cellular pseudopodia, which makes invagination through an actin-mediated pathway possible. It has been proven that the invagination event also requires the participation of the host cell dynamin, actin fibers, microtubules and lipid rafts. Work has emerged investigating mutations in the proline-rich terminal domain (PRD) and their impact on disease development. Salivary antimicrobial peptides are early protective factors against microbial attack. Of great interest is fibronectin (FN) as the main competitor of P. gingivalis fimbriae. The FN can interact with cells in three different regions: the central cell-binding domain (CCBD), the COOH terminal heparin-binding domain (Hep2), and the type III connecting segment (IIICS), including the CS1 region (Yamada, 1991). CCBD is the major cell-adhesion domain of FN and contains an Arg–Gly–Asp (RGD) motif that is recognized by members of the cell adhesion receptor integrin family, including a5b1, which is the primary FN receptor in many cell types. The work focuses on identifying the relationship between the development of periodontitis and the presence of mutations in the adhesion domains of salivary proteins such as cellular fibronectin (cFN) and dynamin-2 (DYNM2).","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"45 6-7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123378596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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