PMID- 29843069 OWN - NLM STAT- MEDLINE DCOM- 20181115 LR - 20211204 IS - 1532-8198 (Electronic) IS - 1092-9134 (Linking) VI - 35 DP - 2018 Aug TI - Evaluation of cMET aberration by immunohistochemistry and fluorescence in situ hybridization (FISH) in triple negative breast cancers. PG - 69-76 LID - S1092-9134(18)30114-X [pii] LID - 10.1016/j.anndiagpath.2018.04.004 [doi] AB - PURPOSE: To evaluate the incidence of cMET proto-oncogene aberration in a cohort of triple negative breast cancers using immunohistochemistry and fluorescence in situ hybridization (FISH) methods and correlated with patient outcome. PATIENTS AND METHODS: One hundred and six female patients with diagnosis of triple negative invasive breast carcinoma at The University of Texas-M D Anderson Cancer Center from 1983 to 2009 were included in the study. Expression of cMET was assessed by IHC using rabbit monoclonal anti-total cMET antibody (SP44 from Ventana). Staining intensity was scored on a scale of 0, 1+, 2+ and 3+. cMET overexpression was defined as at least moderate membranous/cytoplasmic staining in >/=50% of tumor cells (score >/= 2+). FISH analysis was performed using MET (7q31) specific probe (BAC clone RP11-95i20, Abbott Molecular Inc.) and the centromere probe (CEP7/D7Z1, Abbott Molecular Inc.) as internal control. cMET amplification was defined as gene copy numbers >/=4 per cell or cMET/CEP7 ratio >/= 2. cMET status was tested for correlation using Fisher's exact test with other clinicopathological parameters. The Kaplan-Meier product limit method was used to estimate the survival outcomes. Cox proportional hazards models were fit to determine the association of cMET status by IHC, or by FISH, or by copy number with survival outcomes after adjustment for other patient and disease characteristics. RESULTS: Medium follow up is 69.4 months (range 9-317 months). cMET was successfully evaluated by both IHC and FISH methods in ninety-six patients. There were 13 patients whose tumors overexpressed cMET was by IHC. Two patients had cMET amplification by FISH using definitive of cMET/CEP7 ratio of >/=2 and four patients had cMET copy number >4. Only one patient showed cMET/CEP7 ratio of 2.53 and one was positive for cMET overexpression by IHC. No significant association between cMET overexpression by IHC and by FISH using cut-off of with either cMET/CEP7 ratio of >/=2 or cMET copy number of >4 (P = 1.0). There was no significant correlation between the cMET overexpression and other clinicopathological characteristics, such as patient demographics, tumor grade, stage, or chemotherapy treatment history. cMET overexpression and gene amplification did not correlate with the prognosis of TNBC regarding OS or DFS. CONCLUSION: MET amplification is a rare incidence in TNBCs. cMET overexpression is infrequent in TNBCs and may not be driven by gene amplification. Neither have significant prognostic value nor do they correlate with other clinicopathological characteristics in this TNBC cohort. CI - Published by Elsevier Inc. FAU - Wang, Mopei AU - Wang M AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA; Department of Tumor Chemotherapy and Radiation Sickness, Peking University Third Hospital, Beijing 100191, China. FAU - Liang, Li AU - Liang L AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA; Department of Tumor Chemotherapy and Radiation Sickness, Peking University Third Hospital, Beijing 100191, China. FAU - Lei, Xiudong AU - Lei X AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA. FAU - Multani, Asha AU - Multani A AD - Department of Genetics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA. FAU - Meric-Bernstam, Funda AU - Meric-Bernstam F AD - Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 455, Houston, TX 77030, USA. Electronic address: fmeric@mdanderson.org. FAU - Tripathy, Debasish AU - Tripathy D AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA. FAU - Wu, Yun AU - Wu Y AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA. FAU - Chen, Hui AU - Chen H AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA. FAU - Zhang, Hong AU - Zhang H AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX 77030, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. Electronic address: zhangh3@mskcc.org. LA - eng PT - Journal Article DEP - 20180503 PL - United States TA - Ann Diagn Pathol JT - Annals of diagnostic pathology JID - 9800503 RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Carcinoma, Ductal, Breast/*genetics/metabolism/pathology MH - Female MH - *Gene Amplification MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Middle Aged MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins c-met/*genetics MH - Triple Negative Breast Neoplasms/*genetics/metabolism/pathology OTO - NOTNLM OT - Breast Cancer OT - FISH OT - Immunohistochemistry OT - Triple Negative OT - cMET EDAT- 2018/05/31 06:00 MHDA- 2018/11/16 06:00 CRDT- 2018/05/30 06:00 PHST- 2018/04/16 00:00 [received] PHST- 2018/04/18 00:00 [accepted] PHST- 2018/05/31 06:00 [pubmed] PHST- 2018/11/16 06:00 [medline] PHST- 2018/05/30 06:00 [entrez] AID - S1092-9134(18)30114-X [pii] AID - 10.1016/j.anndiagpath.2018.04.004 [doi] PST - ppublish SO - Ann Diagn Pathol. 2018 Aug;35:69-76. doi: 10.1016/j.anndiagpath.2018.04.004. Epub 2018 May 3.