Neuzillet Cindy, Couvelard Anne, Tijeras-Raballand Annemilaï, de Mestier Louis, de Gramont Armand, Bédossa Pierre, Paradis Valérie, Sauvanet Alain, Bachet Jean-Baptiste, Ruszniewski Philippe, Raymond Eric, Hammel Pascal, Cros Jérôme
INSERM UMR1149.
Department of Digestive Oncology, Beaujon University Hospital, Clichy, France.
Histopathology. 2015 Nov;67(5):664-76. doi: 10.1111/his.12691. Epub 2015 May 12.
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.
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.
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.
c-Met是胰腺导管腺癌（PDAC）中一种新兴的生物标志物；对于该标志物的免疫染色评分方法尚无共识。我们旨在评估c-Met过表达在切除的PDAC中的预后价值，并在此背景下制定一种可靠且可重复的c-Met免疫染色评分方法。
在I-II期PDAC中，根据经过验证的MetMab评分（一种结合表面和强度的经典视觉量表，即SI评分）或简化评分（高c-Met：≥20%的肿瘤细胞具有强膜染色）对c-Met免疫染色进行分级。开发了一种计算机辅助分类方法（Aperio软件）。临床病理参数与无病生存期（DFS）和总生存期（OS）相关。对149例患者进行了回顾性两步分析。37个样本（全切片）作为预试验进行分析。简化评分的重复性值最佳（kappa = 0.773）；高c-Met表达（7/37）与较短的DFS [风险比（HR）3.456，P = 0.0036]和OS（HR 4.257，P = 0.0004）相关。87.9%的样本在全切片和组织微阵列上c-Met表达一致，并且可以用特定的计算机辅助算法进行量化。在整个队列（n = 131）中，c-Met（高）肿瘤患者（36/131）在单变量和多变量分析中DFS（9.3个月对20.0个月，HR 2.165，P = 0.0005）和OS（18.2个月对35.0个月，HR 1.832，P = 0.0098）显著缩短。
简化的c-Met表达是I-II期PDAC的独立预后标志物，可能有助于识别肿瘤复发风险高和生存期差的患者。
