Journal of Molecular Pathology最新文献_第2页

A Real-World Study Reporting the Use of Foundation Medicine® Testing in Portugal 一项真实世界的研究报告了基础医学®测试在葡萄牙的使用

Journal of Molecular Pathology Pub Date : 2023-07-20 DOI: 10.3390/jmp4030014

R. Pinto, F. Schmitt

{"title":"A Real-World Study Reporting the Use of Foundation Medicine® Testing in Portugal","authors":"R. Pinto, F. Schmitt","doi":"10.3390/jmp4030014","DOIUrl":"https://doi.org/10.3390/jmp4030014","url":null,"abstract":"Foundation Medicine® testing is a next-generation sequence (NGS)-based platform that allows clinicians to obtain the comprehensive genomic profiling (CGP) of several cancers. By using NGS approaches, relevant genomic alterations can be identified in a short timeframe, providing guidance to diagnostic and therapeutic decisions. This study reports the implementation of three commercially available Foundation Medicine® tests in a Portuguese institution and explores the genomic alterations identified. Data obtained from 72 patients tested with Foundation Medicine® between July 2017 and December 2020 were analysed retrospectively. A total of 290 gene alterations were identified, and TP53 was the gene most frequently altered. Among the 67 successfully profiled samples, 37.3% presented a potentially actionable variation. Breast carcinoma represented the most frequent tumour-carrying variation that can be targeted using currently approved drugs. A limited number of potentially actionable variants using approved drugs was found in this study; however, the genomic information provided by Foundation Medicine® may help clinicians in directing cancer patients into clinical trials or to off-label treatments.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131281555","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

Liquid Biopsy in Advanced Colorectal Cancer: Clinical Applications of Different Analytes 晚期结直肠癌液体活检:不同分析物的临床应用

Journal of Molecular Pathology Pub Date : 2023-07-05 DOI: 10.3390/jmp4030013

M. D. Delcuratolo, A. Modrego-Sánchez, M. Bungaro, B. Antón-Pascual, S. Teran, Valentina Dipace, S. Novello, R. García-Carbonero, F. Passiglia, Cristina Graválos-Castro

引用次数: 0

Analytical Validation and Clinical Utilization of the Oncomine Comprehensive Assay Plus Panel for Comprehensive Genomic Profiling in Solid Tumors 实体肿瘤综合基因组图谱的Oncomine综合分析验证和临床应用

Journal of Molecular Pathology Pub Date : 2023-06-07 DOI: 10.3390/jmp4020012

C. Dumur, R. Krishnan, J. Almenara, K. Brown, Kailyn R. Dugan, Christiana Farni, Fatima Z. Ibrahim, Naomi A. Sanchez, Sumra Rathore, D. Pradhan, J. H. Hughes

{"title":"Analytical Validation and Clinical Utilization of the Oncomine Comprehensive Assay Plus Panel for Comprehensive Genomic Profiling in Solid Tumors","authors":"C. Dumur, R. Krishnan, J. Almenara, K. Brown, Kailyn R. Dugan, Christiana Farni, Fatima Z. Ibrahim, Naomi A. Sanchez, Sumra Rathore, D. Pradhan, J. H. Hughes","doi":"10.3390/jmp4020012","DOIUrl":"https://doi.org/10.3390/jmp4020012","url":null,"abstract":"The detection of driver oncogenic variants and the recent identification of tumor-agnostic genomic biomarkers has driven the use of comprehensive genomic profiling (CGP) for disease diagnosis, prognosis, and treatment selection. The Oncomine™ Comprehensive Assay Plus (OCA+) panel uses DNA and RNA to detect single nucleotide variants (SNVs), small insertions/deletions (Indels), and structural variants (SVs) across 501 genes. Moreover, microsatellite instability (MSI), tumor mutational burden (TMB), and homologous recombination deficiency (HRD) status are assessed in a single workflow. Herein, we present the analytical validation and clinical utilization of OCA+. By using commercial reference materials, we found good analytical sensitivity, specificity, and precision for all biomarkers analyzed. The limit of detection (LoD) was validated for SNVs and Indels at 4%, except for Indels located in homopolymeric regions, where the LoD was 10%. An additional set of 81 tumor samples, including cytology smears, were sequenced to assess the clinical utility of the OCA+ across different tumor types. Among the clinical cohort, OCA+ demonstrated 100% accuracy, sensitivity, and specificity for all biomarkers analyzed, except for MSI assessment of endometrial cancer cases, where 83% accuracy and 67% sensitivity were achieved, compared to PCR and IHC. The validation of accuracy and robustness of this assay supports the OCA+’s utility for solid tumor CGP.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121243854","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

Different Subtypes of Osteosarcoma: Histopathological Patterns and Clinical Behaviour 骨肉瘤的不同亚型:组织病理学模式和临床行为

Journal of Molecular Pathology Pub Date : 2023-05-16 DOI: 10.3390/jmp4020011

Emel Rothzerg, Jiake Xu, David Wood

引用次数: 1

Sinonasal Hyalinizing Adenoid Cystic Carcinoma Is Molecularly Different from Its Salivary and Breast Counterparts 鼻窦透明化腺样囊性癌在分子上与涎腺和乳腺腺样囊性癌不同

Journal of Molecular Pathology Pub Date : 2023-05-15 DOI: 10.3390/jmp4020010

E. Alerraqi, Essam Mandour, Mariz Faltas

{"title":"Sinonasal Hyalinizing Adenoid Cystic Carcinoma Is Molecularly Different from Its Salivary and Breast Counterparts","authors":"E. Alerraqi, Essam Mandour, Mariz Faltas","doi":"10.3390/jmp4020010","DOIUrl":"https://doi.org/10.3390/jmp4020010","url":null,"abstract":"Adenoid cystic carcinoma (AdCC) is known to behave differently based on its location, histologic features, and molecular profile. Despite this understanding, efforts to use these molecular findings to develop personalized treatments have not yet been successful. The purpose of this retrospective study is to examine the molecular characteristics of AdCC with various histologic features in three different locations. A reference group of 20 classic cribriform AdCC cases from the parotid gland was included, along with 10 salivary AdCCs (Group 1), 10 sinonasal AdCCs with hyalinization (Group 2), and 10 solid mammary AdCCs with basaloid features (Group 3). Tissue samples were processed and tested using various molecular techniques, and the Wilcoxon signed-rank test was used to compare the different groups. Molecular data were obtained for both common and rare cases of sinonasal, salivary, and mammary AdCCs, revealing differences in molecular features depending on the tumor’s location. The molecular profile of the AdCCs in the experimental group varied depending on the site, with MYB gene rearrangements being common in all cases. We report the first MYB::KMT2C/D fusions in a subset of salivary AdCCs and sinonasal AdCCs but not in mammary adenoid cystic carcinoma with basaloid features. We conclude that co-occurring genetic alterations may vary among different sites and may have implications for the prognosis and treatment plan of AdCC. More research is needed to fully understand the mechanisms of KMT2C and KMT2D mutations in the development and progression of head and neck cancer, including their interactions with the NOTCH pathway.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"63 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133923643","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

Liquid Biopsy in EGFR-Mutated Advanced NSCLC from T790M to MET Amplification: Clinical Implications and Possibilities in the Resistance Setting 从T790M到MET扩增的egfr突变晚期NSCLC的液体活检:临床意义和耐药性设置的可能性

Journal of Molecular Pathology Pub Date : 2023-04-30 DOI: 10.3390/jmp4020009

L. Della Gravara, Ciro Battiloro, Aniello Avellino, F. Caputo, C. D'aniello, D. Rocco

引用次数: 0

Performance of a 7-Type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-Based Cytology 与液体细胞学相比，7型HPV mRNA检测在HPV DNA初筛阳性女性的分类中的作用

Journal of Molecular Pathology Pub Date : 2023-03-25 DOI: 10.3390/jmp4020008

S. Sørbye, Bente Marie Falang, Mona Antonsen

{"title":"Performance of a 7-Type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-Based Cytology","authors":"S. Sørbye, Bente Marie Falang, Mona Antonsen","doi":"10.3390/jmp4020008","DOIUrl":"https://doi.org/10.3390/jmp4020008","url":null,"abstract":"Background: A plethora of data supports HPV-based screening to be the preferred strategy for cervical cancer prevention. The shift to a more sensitive first-line test brings the need of effective triage up for discussion. Currently, most algorithms apply cytology as a triage of HPV-DNA positive women. This study compared the performance of a 7-type HPV-mRNA test to cytology. Methods: From 1 January 2019 until 31 December 2021, cervical samples from 58,029 women were examined at the University Hospital of North Norway. A total of 30.5% (17,684/58,029) fulfilled the criteria for HPV-DNA primary screening. All positive samples were triaged by cytology and followed-up according to national guidelines through 2022. Additionally, a 7-type HPV-mRNA test was applied. The study endpoint was a histologically confirmed high-grade lesion (CIN2+). Results: A total of 5.6% (990/17,684) had positive HPV-DNA test, 97.2% (962/990) with valid HPV-mRNA results. A total of 55.5% (534/962) had abnormal cytology (ASC-US+), and 35.1% (338/962) had a positive HPV-mRNA test. A total of 13.9% (134/962) had CIN2+. The sensitivity (CIN2+) of cytology versus the HPV-mRNA test was 76.1% (102/134) versus 73.1% (98/134), p = 0.67. The specificity was 47.8% (396/828) versus 71.0% (588/624), p < 0.001. PPV was 19.1% (102/534) and 29.0% (98/338), p < 0.001, respectively. The number of colposcopies per CIN2+ detected by cytology and HPV-mRNA test was 5.2 and 3.1. Conclusion: The 7-type HPV mRNA test was significantly more specific than cervical cytology in a triage of HPV-DNA positive women. Using this biomarker as the threshold for colposcopy may better balance the benefits and harms of screening.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123399376","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

Fluorescence In Situ Hybridization (FISH) for the Characterization and Monitoring of Primary Cultures from Human Tumors 荧光原位杂交(FISH)用于人类肿瘤原代培养物的表征和监测

Journal of Molecular Pathology Pub Date : 2023-03-14 DOI: 10.3390/jmp4010007

Ruth Román-Lladó, C. Aguado, N. Jordana-Ariza, Jaume Roca-Arias, S. Rodríguez, E. Aldeguer, Mónica Garzón-Ibáñez, B. García-Peláez, M. Vives-Usano, A. Giménez-Capitán, A. Aguilar, A. Martínez-Bueno, M. G. Cao, F. García-Casabal, S. Viteri, C. Mayo de las Casas, R. Rosell, M. Molina-Vila

{"title":"Fluorescence In Situ Hybridization (FISH) for the Characterization and Monitoring of Primary Cultures from Human Tumors","authors":"Ruth Román-Lladó, C. Aguado, N. Jordana-Ariza, Jaume Roca-Arias, S. Rodríguez, E. Aldeguer, Mónica Garzón-Ibáñez, B. García-Peláez, M. Vives-Usano, A. Giménez-Capitán, A. Aguilar, A. Martínez-Bueno, M. G. Cao, F. García-Casabal, S. Viteri, C. Mayo de las Casas, R. Rosell, M. Molina-Vila","doi":"10.3390/jmp4010007","DOIUrl":"https://doi.org/10.3390/jmp4010007","url":null,"abstract":"Genetic and drug sensitivity assays on primary cultures are not only of basic but also of translational interest and could eventually aid oncologists in the selection of treatments. However, cancer cells need to be identified and differentiated from the non-tumor cells always present in primary cultures. Also, successive passages can change the proportions of these two subpopulations. In this study, we propose fluorescence in situ hybridization (FISH) analysis on cell smears to determine the presence of tumor cells in primary cultures obtained from patients carrying translocations or copy number gains. FISH proved to be an easy, fast, economic, and reliable method of characterizing cell populations, which could be used repeatedly at different passages to monitor variations and to confirm the maintenance of translocations and copy number gains throughout the culture process.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133673035","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

MET Exon 14 Variants in Non-Small Cell Lung Carcinoma: Prevalence, Clinicopathologic and Molecular Features 非小细胞肺癌的MET外显子14变异:患病率，临床病理和分子特征

Journal of Molecular Pathology Pub Date : 2023-02-09 DOI: 10.3390/jmp4010006

Lisi Yuan, H. Mehrotra, Xin He, David S. Bosler

{"title":"MET Exon 14 Variants in Non-Small Cell Lung Carcinoma: Prevalence, Clinicopathologic and Molecular Features","authors":"Lisi Yuan, H. Mehrotra, Xin He, David S. Bosler","doi":"10.3390/jmp4010006","DOIUrl":"https://doi.org/10.3390/jmp4010006","url":null,"abstract":"Somatic MET exon 14 skipping mutations (MET ex14) are targetable driver mutations for non-small cell lung cancer (NSCLC), responsive to MET inhibitors. Objective: This study seeks to further characterize the clinicopathologic features and mutational profile of MET ex14 variant NSCLC. Design: Retrospective review of all MET ex14 tested NSCLC. Testing for selected BRAF, EGFR, HER2, KRAS, and MET mutations was performed using a clinically validated NGS assay, followed by MiSeq sequencing. Variants were classified as significant (Tier1/2) or variants of uncertain significance (VUS) per 2017 AMP/ASCO/CAP Joint Consensus Guidelines. PD-L1 expression was assessed by immunohistochemistry. Results: Of 2296 NSCLCs tested between 2017-7/2019, MET ex14 variants were present in 44 (1.9%). A total of 32 of 44 variants were MET exon 14 skipping, while the other 12 mutations were significant missense (3) or VUS (9). Of nine VUS, five were adjacent to the canonical splice site and likely to impact splicing. Four cases had concomitant mutations. Of 35 cases with known clinical staging, stage 1–2 = 20 (57%), stage 3 = 3 (9%), and stage 4 = 12 (34%). Of 19 resected NSCLSs, histological types and growth pattern included 7 lepidic pattern-predominant. A high percentage of tumors with MET ex14 mutations are positive for PD-L1, and the percentage of cases with PD-L1 expression >50% trends higher in more advanced disease. Conclusions: Most MET variants identified in our cohort (73%) are MET ex14 skipping. The prevalence of MET ex14 variants is 1.9%, and a large percentage of tumors has lower clinical stage and less aggressive pathologic features.","PeriodicalId":124426,"journal":{"name":"Journal of Molecular Pathology","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127456780","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

Acknowledgment to the Reviewers of Journal of Molecular Pathology in 2022 感谢《分子病理学杂志》2022年审稿人

Journal of Molecular Pathology Pub Date : 2023-01-17 DOI: 10.3390/jmp4010005

引用次数: 0