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

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.

• Authors: Cindy Neuzillet, Anne Couvelard, Annemilaï Tijeras-Raballand, Louis de Mestier, Armand de Gramont, Pierre Bédossa, Valérie Paradis, Alain Sauvanet, Jean-Baptiste Bachet, Philippe Ruszniewski, Eric Raymond, Pascal Hammel, Jérôme Cros
• Journal: Histopathology (Histopathology) Vol. 67 Issue 5 Pg. 664-76 (Nov 2015) ISSN: 1365-2559 [Electronic] England
• PMID: 25809563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Biomarkers, Tumor
• Proto-Oncogene Proteins c-met

Topics

• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Carcinoma, Pancreatic Ductal (mortality, pathology)
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry (methods)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Staging
• Pancreatic Neoplasms (mortality, pathology)
• Prognosis
• Proportional Hazards Models
• Proto-Oncogene Proteins c-met (biosynthesis)
• Reproducibility of Results
• Tissue Array Analysis