High c-Met expression in stage I-II pancreatic adenocarcinoma: proposal for an immunostaining scoring method and correlation with poor prognosis.

Details

Serval ID
serval:BIB_6127472F994C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
High c-Met expression in stage I-II pancreatic adenocarcinoma: proposal for an immunostaining scoring method and correlation with poor prognosis.
Journal
Histopathology
Author(s)
Neuzillet C., Couvelard A., Tijeras-Raballand A., de Mestier L., de Gramont A., Bédossa P., Paradis V., Sauvanet A., Bachet J.B., Ruszniewski P., Raymond E., Hammel P., Cros J.
ISSN
1365-2559 (Electronic)
ISSN-L
0309-0167
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
67
Number
5
Pages
664-676
Language
english
Abstract
AIMS: c-Met is an emerging biomarker in pancreatic ductal adenocarcinoma (PDAC); there is no consensus regarding the immunostaining scoring method for this marker. We aimed to assess the prognostic value of c-Met overexpression in resected PDAC, and to elaborate a robust and reproducible scoring method for c-Met immunostaining in this setting.
METHODS AND RESULTS: c-Met immunostaining was graded according to the validated MetMab score, a classic visual scale combining surface and intensity (SI score), or a simplified score (high c-Met: ≥ 20% of tumour cells with strong membranous staining), in stage I-II PDAC. A computer-assisted classification method (Aperio software) was developed. Clinicopathological parameters were correlated with disease-free survival (DFS) and overall survival(OS). One hundred and forty-nine patients were analysed retrospectively in a two-step process. Thirty-seven samples (whole slides) were analysed as a pre-run test. Reproducibility values were optimal with the simplified score (kappa = 0.773); high c-Met expression (7/37) was associated with shorter DFS [hazard ratio (HR) 3.456, P = 0.0036] and OS (HR 4.257, P = 0.0004). c-Met expression was concordant on whole slides and tissue microarrays in 87.9% of samples, and quantifiable with a specific computer-assisted algorithm. In the whole cohort (n = 131), patients with c-Met(high) tumours (36/131) had significantly shorter DFS (9.3 versus 20.0 months, HR 2.165, P = 0.0005) and OS (18.2 versus 35.0 months, HR 1.832, P = 0.0098) in univariate and multivariate analysis.
CONCLUSIONS: Simplified c-Met expression is an independent prognostic marker in stage I-II PDAC that may help to identify patients with a high risk of tumour relapse and poor survival.
Keywords
Adult, Aged, Biomarkers, Tumor/analysis, Carcinoma, Pancreatic Ductal/mortality, Carcinoma, Pancreatic Ductal/pathology, Disease-Free Survival, Female, Humans, Immunohistochemistry/methods, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Pancreatic Neoplasms/mortality, Pancreatic Neoplasms/pathology, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins c-met/biosynthesis, Reproducibility of Results, Tissue Array Analysis
Pubmed
Web of science
Create date
03/11/2015 17:26
Last modification date
20/08/2019 14:18
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