Journal of Molecular Pathology最新文献_第3页

Mutational Profiling of Lung Cancer Using Next Generation Sequencing: A Malaysian Real-World Clinical Diagnostic Experience 使用下一代测序的肺癌突变谱:马来西亚真实世界的临床诊断经验

Journal of Molecular Pathology Pub Date : 2023-01-11 DOI: 10.3390/jmp4010004

P. Rajadurai, N. Yap, Saira Bahnu Mohamed Yousoof, Y. Cheah

{"title":"Mutational Profiling of Lung Cancer Using Next Generation Sequencing: A Malaysian Real-World Clinical Diagnostic Experience","authors":"P. Rajadurai, N. Yap, Saira Bahnu Mohamed Yousoof, Y. Cheah","doi":"10.3390/jmp4010004","DOIUrl":"https://doi.org/10.3390/jmp4010004","url":null,"abstract":"Lung cancer is one of the most common cancers and a leading cause of cancer-related mortality in Malaysia. This analysis aimed to evaluate the prevalence of actionable and common mutations, as well as co-mutations frequently occurring with EGFR variants in lung cancer. Mutational profiling of lung tumour samples was performed using next generation sequencing (NGS) panels at the Subang Jaya Medical Centre laboratory. A total of 469 lung tumour samples referred from several medical facilities in Malaysia were analysed and 84% were of the adenocarcinoma subtype. The three most frequent mutations found were EGFR (46.5%), TP53 (37.5%) and KRAS (14.3%). Actionable mutations with approved drug targets for lung cancer were detected in 63.5% of patient samples. Among patients with EGFR mutations, deletions in exon 19 were detected in 44.5% and p.L858R in 38.5% of samples. The most common co-mutations for samples with EGFR mutations were found in the TP53 gene (38.1%). A median turnaround time (TAT) of 3 working days was achievable with an automated NGS platform. NGS testing can provide valuable information on the mutational landscape and the prevalence of common or actionable mutations present in lung cancer patients. This real-world experience demonstrates the high percentage of actionable mutations detected and highlights the value of NGS testing in a clinical diagnostic setting.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129067790","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}

引用次数: 1

Juggling the Various Facets of Modern Anatomic Pathology: A Perspective 杂耍现代解剖病理学的各个方面:一个视角

Journal of Molecular Pathology Pub Date : 2023-01-09 DOI: 10.3390/jmp4010003

P. Pisapia, G. Troncone

引用次数: 0

Platelet Concentration and Platelet/Lymphocyte Ratio as Prognostic Indicators in Luminal Breast Cancer 血小板浓度和血小板/淋巴细胞比值作为腔内乳腺癌的预后指标

Journal of Molecular Pathology Pub Date : 2023-01-02 DOI: 10.3390/jmp4010002

Â. D. R. O. Rönnau, Maiquidieli Dal Berto, C. Bica, R. Alves, L. Rotta

{"title":"Platelet Concentration and Platelet/Lymphocyte Ratio as Prognostic Indicators in Luminal Breast Cancer","authors":"Â. D. R. O. Rönnau, Maiquidieli Dal Berto, C. Bica, R. Alves, L. Rotta","doi":"10.3390/jmp4010002","DOIUrl":"https://doi.org/10.3390/jmp4010002","url":null,"abstract":"Ratios between the blood cells are indirect measures of the imbalance in the pro-inflammatory status observed in carcinogenesis and have been proposed as accessible and feasible biomarkers to predict cancer prognosis. We aim to evaluate the prognostic significance of neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte (PLR) ratios in Brazilian patients with luminal breast cancer (LBC) treated with tamoxifen. A retrospective cohort of 72 operable LBC patients. Preoperative leukocyte and platelet absolute values permitted to calculate NLR, MLR, and PLR. Area under curve (ROC) determined the cutoff value associated with relapse and death. Univariate and multivariate analyses were used to assess the relationship of the platelet and PLR to disease-free survival (DFS) and overall survival (OS). Lower DFS was associated with >297 × 103/mm3 (54 vs. 60.9 months in <297, p = 0.04). Platelet > 279 × 103/mm3 are related to higher OS (p = 0.03). Univariate analysis revealed that platelet concentration was associated with DFS (p = 0.04) and OS (p = 0.04), but not as an independent factor (HR = 1.31, 95%CI: 0.42–4.07, p = 0.65) and OS (HR = 1.64, 95%CI: 0.28–9.52, p = 0.58). Both univariate (p = 0.01) and multivariate analysis revealed that PLR < 191.5 was a significant independent predictor of higher OS/better prognosis (HR = 16.16, 95%CI: 2.83–109.25, p = 0.00). Pretreatment platelet indices (absolute count and PLR) are prognosis predictors in LBC patients. Platelet > 279 × 103/mm3 and PRL < 191.5 was associated with a higher OS, with the PRL being an independent predictor of higher OS.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126212996","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}

引用次数: 0

Metastatic Breast Cancer: Cytology Diagnosis with Implications for Treatment 转移性乳腺癌:细胞学诊断与治疗的意义

Journal of Molecular Pathology Pub Date : 2022-12-24 DOI: 10.3390/jmp4010001

A. Hrizat, E. Brachtel

{"title":"Metastatic Breast Cancer: Cytology Diagnosis with Implications for Treatment","authors":"A. Hrizat, E. Brachtel","doi":"10.3390/jmp4010001","DOIUrl":"https://doi.org/10.3390/jmp4010001","url":null,"abstract":"Breast cancer is among the most frequent malignancies in women worldwide. While early detection and effective treatment provide many women with a cure and prevent their cancer from spreading, metastases to distant sites still occur in around 20% of women suffering from breast cancer. These relapses occur in many forms and locations and are as varied as the primary breast tumors. Metastatic spread makes a cancer incurable and potentially lethal, but new, targeted treatments can offer control of the cancer cells if the features of new targets are unlocked by advanced diagnostic testing. The article offers an overview of the pathomechanisms of metastatic progression and describes the types of metastases, such as hormone-receptor-positive and -negative breast cancers, and HER2-overexpressing or triple-negative types. Once distant metastatic spread occurs, cytology allows a precise diagnosis to confirm the breast origin. Other molecular targets include ESR1 and PIK3CA mutations, MSI, NTRK fusion, PD-L1 expression and others, which can be obtained also from cytology material and used to determine eligibility for emerging targeted therapeutic options. We outline the diagnostic features of metastatic breast cancer in cytology samples, together with validated and emergent biomarkers that may provide new, targeted treatment options.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122172332","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}

引用次数: 1

Intertwining Neuropathogenic Impacts of Aberrant Circadian Rhythm and Impaired Neuroregenerative Plasticity in Huntington’s Disease: Neurotherapeutic Significance of Chemogenetics 异常昼夜节律和受损神经再生可塑性在亨廷顿舞蹈病中相互交织的神经致病影响:化学遗传学的神经治疗意义

Journal of Molecular Pathology Pub Date : 2022-12-09 DOI: 10.3390/jmp3040030

Sowbarnika Ravichandran, R. Suhasini, Sudhiksha Madheswaran Deepa, D. Selvaraj, Jemi Feiona Vergil Andrews, V. Thiagarajan, M. Kandasamy

{"title":"Intertwining Neuropathogenic Impacts of Aberrant Circadian Rhythm and Impaired Neuroregenerative Plasticity in Huntington’s Disease: Neurotherapeutic Significance of Chemogenetics","authors":"Sowbarnika Ravichandran, R. Suhasini, Sudhiksha Madheswaran Deepa, D. Selvaraj, Jemi Feiona Vergil Andrews, V. Thiagarajan, M. Kandasamy","doi":"10.3390/jmp3040030","DOIUrl":"https://doi.org/10.3390/jmp3040030","url":null,"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, 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114174999","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}

引用次数: 0

DNA Mismatch Repair Proteins and BRAF V600E Detection by Immunohistochemistry in Colorectal Cancer Demonstrates Concordance with Next Generation Sequencing 结直肠癌DNA错配修复蛋白和BRAF V600E免疫组化检测与下一代测序结果一致

Journal of Molecular Pathology Pub Date : 2022-12-02 DOI: 10.3390/jmp3040029

Joel Yambert, L. A. Henricksen, June Clements, Andrew Hannon, Alyssa Jordan, Shalini Singh, K. Dvorak, C. Pritchard, Eric Q. Konnick

{"title":"DNA Mismatch Repair Proteins and BRAF V600E Detection by Immunohistochemistry in Colorectal Cancer Demonstrates Concordance with Next Generation Sequencing","authors":"Joel Yambert, L. A. Henricksen, June Clements, Andrew Hannon, Alyssa Jordan, Shalini Singh, K. Dvorak, C. Pritchard, Eric Q. Konnick","doi":"10.3390/jmp3040029","DOIUrl":"https://doi.org/10.3390/jmp3040029","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124967703","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}

引用次数: 0

Optimal Assessment of Metastatic Breast Carcinoma: The Value of Cytopathology Combined with Molecular Analysis 转移性乳腺癌的最佳评估:细胞病理学结合分子分析的价值

Journal of Molecular Pathology Pub Date : 2022-11-22 DOI: 10.3390/jmp3040028

Ricella Souza da Silva, F. Schmitt

{"title":"Optimal Assessment of Metastatic Breast Carcinoma: The Value of Cytopathology Combined with Molecular Analysis","authors":"Ricella Souza da Silva, F. Schmitt","doi":"10.3390/jmp3040028","DOIUrl":"https://doi.org/10.3390/jmp3040028","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128813375","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}

引用次数: 1

The p16 Antagonist Gankyrin Is Overexpressed in Melanocytic Neoplasms p16拮抗剂Gankyrin在黑色素细胞肿瘤中过度表达

Journal of Molecular Pathology Pub Date : 2022-11-21 DOI: 10.3390/jmp3040027

S. Moradi, T. Ehrig

{"title":"The p16 Antagonist Gankyrin Is Overexpressed in Melanocytic Neoplasms","authors":"S. Moradi, T. Ehrig","doi":"10.3390/jmp3040027","DOIUrl":"https://doi.org/10.3390/jmp3040027","url":null,"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 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.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128008068","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}

引用次数: 0

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 基于rna的下一代测序在非小细胞肺癌(NSCLC)的集中模型中进行体细胞分子检测:现实世界数据表明是时候重新考虑检测选择了

Journal of Molecular Pathology Pub Date : 2022-11-08 DOI: 10.3390/jmp3040026

A. Finall

引用次数: 1

Comprehensive Review of Metastatic Breast Carcinoma in Cytology Specimens 转移性乳腺癌细胞学标本的综合综述

Journal of Molecular Pathology Pub Date : 2022-11-07 DOI: 10.3390/jmp3040025

S. U. Baskota, Daniel Qazi, A. Chandra, Poonam Vohra

引用次数: 0