Distinction between multiple primary cancers and intrapulmonary metastases in patients with synchronous multifocal lung cancer can be challenging. Histological and genotypic assessment of multifocal lung tumors have been suggested to influence the staging. The aim of this study was to determine the role of morphology and genotype in staging of surgically treated multifocal non-small cell lung carcinoma. Synchronous lung cancers from 60 patients (42 with adenocarcinoma and 18 with squamous cell carcinoma), clinically considered to represent intrapulmonary metastases, were histologically subtyped according to the 2015 World Health Organization classification of lung tumors and subjected to genotypic analysis (KRAS, EGFR, BRAF, PIK3CA, ALK, MET and ROS1 in adenocarcinoma and PIK3CA and p16 in squamous cell carcinoma). Concordance between clinical criteria and histological subtyping was identified in about 50% of cases (Po 0.0001). Genotypically, 44% of adenocarcinomas and 60% of squamous cell carcinomas with identified molecular alterations were considered to be intrapulmonary metastases. Concordance between histological and molecular staging was observed in 89% of adenocarcinomas and 56% of squamous cell carcinomas. Univariate survival analyses failed to demonstrate significant differences in overall or cancer-specific survival in patients with adenocarcinoma and squamous cell carcinomas restaged according to histology and/or molecular profile. Lymph node metastases (N1/N2 vs N0) (P = 0.03) and age 465 years (P = 0.05) were associated with shorter overall survival. In addition, squamous cell carcinomas with p16 deletion showed shorter overall survival when compared with squamous cell carcinomas without p16 deletion (P = 0.05). No correlation between other molecular alterations, clinico-pathological characteristics and prognosis was found. Our study demonstrates that a comprehensive genotypic and morphological assessment of surgically treated multifocal lung cancers is feasible but not sufficient to establish their clonal relationship and prognosis. Modern Pathology (2016) 29, 735-742; doi:10.1038/modpathol.2016 published online 15 April 2016 The reported incidence of multiple synchronous tumors of the lung in recent series is up to 20%. 1,2 Staging of such tumors as independent primary tumors or intrapulmonary metastases is often challenging. Morphological criteria, especially those proposed by Martini and Melamed, 3 have been used as the main tool with the idea that morphology of metastases should match the primary tumor, while different morphology supports classification of tumors as unrelated separate primaries. However, clinico-pathological distinction between the two possibilities is not always possible and may not be prognostic.Over the past decade, multiple studies using different molecular approaches to analysis of synchronous lung tumor nodules have emerged, including DNA microsatellite analysis, CGH/aCHG and most recently next-generation sequencing. 2,[4][5][6][7][8][9][10] The data from published rep...
Triple negative breast cancer (TNBC) is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity. Patients with TNBC frequently undergo an aggressive clinical course due to the unavailability of specific targeted therapies. Androgen receptor (AR) was reported to be expressed in up to 60% of TNBC cases but there have been controversies as to the roles of androgen signaling through AR in TNBC. Therefore, in this study, we analyzed the status of AR in combination with androgen synthesizing enzymes (5a-reductase type 1 (5aR1) and 17b-hydroxysteroid dehydrogenase type 5 (17bHSD5)] in order to further understand androgenic actions in TNBC. Androgen receptor, 5aR1, and 17bHSD5 were immunolocalized in a cohort of 203 TNBC patients from Thailand and Japan. We then correlated the findings with clinicopathological characteristics (age, stage, tumor diameter, lymph node invasion, metastatic spread, Ki-67 labeling index, disease-free survival, and overall survival) of the patients. Univariate analysis revealed that AR+/enzyme+ cases were associated with a significantly lower Ki-67 labeling index than AR−/enzyme− samples. Multivariate analysis indicated the presence of significant positive correlations between AR and enzyme status in tumor cells, and between tumor diameter, lymph node invasion, and distant metastasis. Significant negative correlations were also detected between Ki-67 labeling index and AR status (P = 0.04) or 5aR1 (P < 0.001). Cox proportional hazards analysis showed that Ki-67 labeling index and stage were the only factors predicting disease-free and overall survival of the patients, although univariate KaplanMeier analysis revealed AR/5aR1 negativity suggested a more adverse clinical course up to 80 months after surgery. These results suggest that the presence of androgen synthesizing pathways in addition to AR expression in tumor cells could confer a better clinical outcome through suppression of cell proliferation. (Cancer Sci 2013; 104: 639-646) B reast cancer is the most common malignancy in women (1) and, although recent advances in clinical management have significantly improved the survival rates of the great majority of breast cancer patients, (2) one subtype, so-called triple negative breast cancer (TNBC) continues to be associated with an adverse prognosis.(3) Triple negative breast cancer is characterized by the absence of estrogen receptor-a (ERa), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression in the tumor cells and constitutes approximately 6-60% of all breast cancer cases, depending on the cohort evaluated. (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) This subtype is considered to be far more diverse compared to other subtypes of breast malignancy. (24)(25)(26) Triple negative breast cancer is generally associated with relatively adverse clinical outcome (27)(28)(29)(30) primarily due to the lack of specific therapies, higher rates of tumor cell proliferation, and m...
In MPE, CB provides a similar diagnostic performance to CS, while application of both techniques can significantly increase the diagnostic yield. However, in other pleural diseases, CB and CS had limited values in diagnosis.
Break-apart ALK FISH probe is the FDA approved approach for detection of ALK rearrangements in lung carcinoma patients who may benefit from ALK kinase inhibitors. The FISH assay can be technically challenging and difficult to interpret. ALK immunohistochemistry and next generation sequencing have been proposed as alternative approaches. In this study, we compared various ALK –FISH patterns to next –generation sequencing (NGS) for gene fusion detection, ALK immunohistochemistry (IHC) and tumor responses to crizotinib. 72 (4%) of 2116 lung adenocarcinoma were positive by ALK- FISH. Of 28 ALK-FISH positive cases selected for the study, FISH patterns included 15 (54%) cases with split signal, 10 (36%) with single orange signal and 3 (10%) with “mixed pattern”. 12 (80%) cases with split signal and 4 (40%) cases with single orange signal were positive by NGS and IHC, while mixed cases were all negative. Mutation analysis of discordant cases revealed multiple mutations including oncogenic mutations in EGFR, KRAS, BRAF and ATM genes. All discordant cases in groups with split and mixed signal showed a lower number of cells with rearrangement (mean 28.5%; range 20.5-36.9%). No statistically significant association between response to crizotinib and FISH patterns was observed (p=0.73). In contrast, NGS fusion positive cases were associated with more responses to crizotinib than NGS negative cases (p= 0.016). Our study suggests that ALK FISH alone may not be the most reliable assay for detection of ALK gene rearrangements, and probably should be used in parallel with ALK IHC and NGS for detection of gene fusions and mutations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.