Journal of Molecular Pathology最新文献_第8页

Challenges of ICC and FISH in the Field of Targeted Therapies from Cell Block to Smears ICC和FISH在从细胞阻滞到涂片的靶向治疗领域的挑战

Journal of Molecular Pathology Pub Date : 2021-03-30 DOI: 10.3390/JMP2020006

J. Echeveste, T. Labiano, E. Tejerina, A. Argueta, C. D. de Andrea, M. Lozano

{"title":"Challenges of ICC and FISH in the Field of Targeted Therapies from Cell Block to Smears","authors":"J. Echeveste, T. Labiano, E. Tejerina, A. Argueta, C. D. de Andrea, M. Lozano","doi":"10.3390/JMP2020006","DOIUrl":"https://doi.org/10.3390/JMP2020006","url":null,"abstract":"In the era of personalized medicine, there is an increasing demand for comprehensive and complex diagnosis using minimally invasive techniques. Nowadays, it is mandatory to integrate biomarkers in the diagnostic process, as well as in the treatment and clinical management of many cancer patients. Patients with non-small cell lung cancer (NSCLC), for instance, are frequently diagnosed in advanced stages, at a point when only cytological material or small biopsies can be obtained. This pathology constitutes an interesting challenge for the testing of biomarkers in cytology. Furthermore, there is a growing development of imaging techniques that guide non-invasive approaches to obtain small biopsies or cytological samples. This has allowed fine needle aspiration cytology and fine needle aspiration biopsy (FNAC, FNAB) to become front-line procedures in the management of patients with NSCLC. It is well known that the list of biomarkers to be tested in these patients continues to increase. Nevertheless, there are several of essential biomarkers that should always be analyzed in all patients with NSCLC, not only in non-squamous but also in some squamous carcinomas (SqCC). Some of them, such as PDL1, are tested by immunocytochemistry (ICC), while others, mainly ALK and ROS1, can be tested by ICC and confirmed using other techniques such a Fluorescence In Situ Hybridization (FISH). Other biomarkers, namely EGFR and BRAF mutations, are currently evaluated by polymerase chain reaction (PCR)-based techniques including Next-Generation Sequencing (NGS). In this review, we will address the particularities and challenges that ICC and FISH pose in different types of cytological samples from an eminently practical point of view.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123849405","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

PIK3CA Mutation Assessment in HR+/HER2− Metastatic Breast Cancer: Overview for Oncology Clinical Practice HR+/HER2−转移性乳腺癌中PIK3CA突变评估:肿瘤学临床实践概述

Journal of Molecular Pathology Pub Date : 2021-03-11 DOI: 10.3390/JMP2010005

C. Criscitiello, A. Marra, G. Curigliano

{"title":"PIK3CA Mutation Assessment in HR+/HER2− Metastatic Breast Cancer: Overview for Oncology Clinical Practice","authors":"C. Criscitiello, A. Marra, G. Curigliano","doi":"10.3390/JMP2010005","DOIUrl":"https://doi.org/10.3390/JMP2010005","url":null,"abstract":"Activation of the PI3K–AKT–mTOR pathway occurs in several human cancers, including hormone receptor (HR)-positive breast cancer (BC) where is associated with resistance to endocrine therapy and disease progression. In BC, the most common PI3K–AKT–mTOR pathway alteration is represented by PIK3CA oncogenic mutations. These mutations can occur throughout several domains of the p110α catalytic subunit, but the majority are found in the helical and kinase domains (exon 9 and 20) that represent the “hotspots”. Considering the central role of the PI3K–AKT–mTOR pathway in HR-positive BC, several inhibitors (both pan-PI3K and isoform-specific) have been developed and tested in clinical trials. Recently, the PI3Kα-selective inhibitor alpelisib was the first PI3K inhibitor approved for clinical use in HR-positive metastatic BC based on the results of the phase III SOLAR-1 trial. Several methods to assess PIK3CA mutational status in tumor samples have been developed and validated, including real-time polymerase chain reaction (PCR), digital droplet PCR (ddPCR), BEAMing assays, Sanger sequencing, and next-generation sequencing (NGS) panels. Several new challenges will be expected once alpelisib is widely available in a clinical setting, including the harmonization of testing procedures for the detection of PI3K–AKT–mTOR pathway alterations. Herein, we provide an overview on PI3K–AKT–mTOR pathway alterations in HR-positive BC, discuss their role in determining prognosis and resistance to endocrine therapy and highlight practical considerations about diagnostic methods for the detection of PI3K–AKT–mTOR pathway activation status.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126263288","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: 6

Collection and Handling of Thoracic Small Biopsy and Cytology Specimens for Ancillary Studies: Guidelines from the College of American Pathologists (CAP) 辅助研究胸部小活检和细胞学标本的收集和处理:美国病理学家学会(CAP)指南

Journal of Molecular Pathology Pub Date : 2021-03-01 DOI: 10.3390/JMP2010003

S. Roy-Chowdhuri

引用次数: 0

Practical Applications of Molecular Testing in the Cytologic Diagnosis of Pancreatic Cysts 分子检测在胰腺囊肿细胞学诊断中的实际应用

Journal of Molecular Pathology Pub Date : 2021-02-07 DOI: 10.3390/JMP2010002

M. Zhang, M. Pitman

{"title":"Practical Applications of Molecular Testing in the Cytologic Diagnosis of Pancreatic Cysts","authors":"M. Zhang, M. Pitman","doi":"10.3390/JMP2010002","DOIUrl":"https://doi.org/10.3390/JMP2010002","url":null,"abstract":"Mucinous pancreatic cysts are precursor lesions of ductal adenocarcinoma. Discoveries of the molecular alterations detectable in pancreatic cyst fluid (PCF) that help to define a mucinous cyst and its risk for malignancy have led to more routine molecular testing in the preoperative evaluation of these cysts. The differential diagnosis of pancreatic cysts is broad and ranges from non-neoplastic to premalignant to malignant cysts. Not all pancreatic cysts—including mucinous cysts—require surgical intervention, and it is the preoperative evaluation with imaging and PCF analysis that determines patient management. PCF analysis includes biochemical and molecular analysis, both of which are ancillary studies that add significant value to the final cytological diagnosis. While testing PCF for carcinoembryonic antigen (CEA) is a very specific test for a mucinous etiology, many mucinous cysts do not have an elevated CEA. In these cases, detection of a KRAS and/or GNAS mutation is highly specific for a mucinous etiology, with GNAS mutations supporting an intraductal papillary mucinous neoplasm. Late mutations in the progression to malignancy such as those found in TP53, p16/CDKN2A, and/or SMAD4 support a high-risk lesion. This review highlights PCF triage and analysis of pancreatic cysts for optimal cytological diagnosis.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"543 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114090958","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: 2

Concomitant Rare KRAS and BRAF Mutations in Lung Adenocarcinoma: A Case Report 罕见KRAS和BRAF突变在肺腺癌中的合并:1例报告

Journal of Molecular Pathology Pub Date : 2020-11-03 DOI: 10.3390/jmp1010006

A. Iaccarino, P. Pisapia, M. De Felice, F. Pepe, Gianluca Gragnano, C. De Luca, G. Ianniello, U. Malapelle

{"title":"Concomitant Rare KRAS and BRAF Mutations in Lung Adenocarcinoma: A Case Report","authors":"A. Iaccarino, P. Pisapia, M. De Felice, F. Pepe, Gianluca Gragnano, C. De Luca, G. Ianniello, U. Malapelle","doi":"10.3390/jmp1010006","DOIUrl":"https://doi.org/10.3390/jmp1010006","url":null,"abstract":"In July 2020, an active smoker, 63-year old man was admitted to the oncology unit of A.O.R.N. Sant’Anna e San Sebastiano (Caserta, Italy). Chest radiology highlighted right pleural effusion. Total-body CT scanning revealed a solid lesion with lobulated contours in the apical segment of the upper right lobe. The patient’s oncologist requested a molecular assessment of EGFR, ALK, ROS1, BRAF, and KRAS, as well as an evaluation of PD-L1 expression level. To this end, we carried out NGS analysis, on DNA extracted from cytospins, by adopting a custom-designed NGS panel (SiRe®). Overall, no actionable mutations in the tested genes were identified. Conversely, concomitant BRAF exon 11 p.G469A and a KRAS exon 4 p.A146T mutations were detected. Owing to the limited data on the presence of KRAS exon 4 p.A146T point mutation in lung adenocarcinoma patients, a further molecular confirmatory analysis was carried out with a dedicated KRAS cartridge on a fully automated real time polymerase chain reaction. When DNA was extracted from the TTF-1 positive tumor cell slide, the same KRAS alteration was observed. Unfortunately, the patient died in August 2020 before having the chance to start any type of treatment.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"218 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124318143","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

Persistent Ependymal Tumor Arising from an Immature Ovarian Teratoma: A Rare Case 未成熟卵巢畸胎瘤致持续性室管膜肿瘤一例

Journal of Molecular Pathology Pub Date : 2020-10-05 DOI: 10.3390/JMP1010005

Anoshia Afzal, R. Lu, S. Asadbeigi, K. Fung, J. Peterson

引用次数: 0

ROC Analysis Identifies Baseline and Dynamic NLR and dNLR Cut-Offs to Predict ICI Outcome in 402 Advanced NSCLC Patients 在402例晚期NSCLC患者中，ROC分析确定了基线和动态NLR和dNLR临界值来预测ICI结果

Journal of Molecular Pathology Pub Date : 2020-09-15 DOI: 10.3390/JMP1010004

S. Carnio, A. Mariniello, P. Pizzutilo, G. Numico, G. Borra, A. Lunghi, H. S. Soto Parra, R. Buosi, T. Vavalà, I. Stura, S. Genestroni, A. Alemanni, F. Arizio, A. Catino, M. Montrone, F. Tabbò, D. Galetta, G. Migliaretti, S. Novello

{"title":"ROC Analysis Identifies Baseline and Dynamic NLR and dNLR Cut-Offs to Predict ICI Outcome in 402 Advanced NSCLC Patients","authors":"S. Carnio, A. Mariniello, P. Pizzutilo, G. Numico, G. Borra, A. Lunghi, H. S. Soto Parra, R. Buosi, T. Vavalà, I. Stura, S. Genestroni, A. Alemanni, F. Arizio, A. Catino, M. Montrone, F. Tabbò, D. Galetta, G. Migliaretti, S. Novello","doi":"10.3390/JMP1010004","DOIUrl":"https://doi.org/10.3390/JMP1010004","url":null,"abstract":"Background: Neutrophil-to-Lymphocyte Ratio (NLR) and derived Neutrophils-to-(Leukocytes minus neutrophils) Ratio (dNLR) have been proposed as possible biomarkers of response to immune checkpoint inhibitors (ICI). However, in non-small cell lung cancer (NSCLC) studies, various NLR and/or dNLR cut-offs have been used, manly based on previous reports on melanoma. Methods: In this Italian multicenter retrospective study, NLR, dNLR, platelet-to-lymphocyte ratio, albumin, and lactate dehydrogenase (LDH) were longitudinally assessed in patients with stage IV non-small cell lung cancer (NSCLC) treated with ICI. The primary objective was to evaluate if baseline parameters predicted response to ICI, using Receiver Operating Characteristic (ROC) curves. Secondary endpoint was to evaluate if dynamic changing of NLR and dNLR also predicted response. Results: Data of 402 patients were collected and analyzed. Among the baseline parameters considered, NLR and dNLR were the most appropriate biomarkers according to the ROC analyses, which also identified meaningful cut-offs (NLR = 2.46; dNLR = 1.61). Patients with low ratios reported a significantly improved outcome, in terms of overall survival (p = 0.0003 for NLR; p = 0.0002 for dNLR) and progression free survival (p = 0.0004 for NLR; p = 0.005 for dNLR). The role of NLR and dNLR as independent biomarkers of response was confirmed in the Cox regression model. When assessing NLR and dNLR dynamics from baseline to cycle 3, a decrease ≥1.04 for NLR and ≥0.41 for dNLR also predicted response. Conclusions in our cohort, we confirmed that NLR and dNLR, easily assessable on peripheral blood, can predict response at baseline and early after ICI initiation. For both baseline and dynamic assessment, we identified clinically meaningful cut-offs, using ROC curves.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131345674","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: 3

Comparison of the Hybrid Capture II Method with a PCR-Based Screening Method Using a Carboxyfluorescein-Labeled Primer for Detecting Human Papillomavirus in Cervicovaginal Liquid-Based Cytology 杂交捕获II法与基于pcr的羧基荧光标记引物筛选法在宫颈阴道液细胞学中检测人乳头瘤病毒的比较

Journal of Molecular Pathology Pub Date : 2020-09-10 DOI: 10.3390/jmp1010003

Y. Saiki, Yuka Gion, Asami Nishikori, Y. Norimatsu, Y. Sato

{"title":"Comparison of the Hybrid Capture II Method with a PCR-Based Screening Method Using a Carboxyfluorescein-Labeled Primer for Detecting Human Papillomavirus in Cervicovaginal Liquid-Based Cytology","authors":"Y. Saiki, Yuka Gion, Asami Nishikori, Y. Norimatsu, Y. Sato","doi":"10.3390/jmp1010003","DOIUrl":"https://doi.org/10.3390/jmp1010003","url":null,"abstract":"Objective: Human papillomaviruses (HPVs) are DNA viruses, of which over 120 types have been identified. The main screening methods for HPV-DNA include the hybrid capture II (HC-II) and polymerase chain reaction (PCR) assays. Liquid-based cytology (LBC) is a high-quality technique developed to improve the diagnostic reliability of traditional Papanicolaou tests (Pap tests). However, relatively few studies have compared the efficacy of PCR and HC-II assays using cervicovaginal LBC specimens. In this study, we conducted a comparative analysis with results derived from the HC-II assay to assess whether a PCR-based assay using a novel carboxyfluorescein (FAM)-labeled primer could be applied to cervicovaginal LBC specimens. Methods and Results: We analyzed 59 specimens diagnosed as atypical squamous cells of undetermined significance (ASCUS) by Pap tests. After extracting DNA from cervicovaginal LBC specimens, we performed PCR using a FAM-labeled consensus primer, and then conducted fragment analysis to confirm the results. The value of the kappa statistic measuring the agreement between the PCR and HC-II results was 0.8557, or “almost perfect agreement.” Conclusion: Our novel HPV-PCR assay can be successfully applied to cervicovaginal LBC specimens for the detection of HPV subtypes.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125007511","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: 3

Are Microsatellite Patterns Specific for Tumor Types? A Pilot Investigation 微卫星模式对肿瘤类型有特异性吗?一项试点调查

Journal of Molecular Pathology Pub Date : 2020-09-04 DOI: 10.3390/jmp1010002

Tiffany Haiduk, M. Brockmann, C. Schmitt, R. Tillmann, Monika Pieper, J. Lüsebrink, O. Schildgen, V. Schildgen

引用次数: 0

The Birth of the Journal of Molecular Pathology 《分子病理学杂志》的诞生

Journal of Molecular Pathology Pub Date : 2020-06-29 DOI: 10.3390/jmp1010001

G. Troncone

引用次数: 0