Morphologic and Immunohistochemical Appraisal of Primary Gastric Carcinomas

Gastric carcinoma management requires adjustments answering their genetic and morphologic heterogeneity. We aim to assess the expression and significance of a myriad of biomarkers (p53, MLH1, MSH2, PMS2, MSH6, Epstein-Barr encoding region-RNA, c-erbB2, E-cadherin, CEA, chromogranin, Ki-67, CDX2, presenilin-1, cathepsin E, MUC5AC, cyclin-dependent kinase 1) in 117 gastric carcinomas, which we have morphologically subclassified with a simple algorithm. Immunohistochemical stains were applied to 3 tissue microarrays of primary gastric carcinomas (n=117) obtained from resection specimens of untreated patients. These cases represented the morphologic subgroups that emerged from a reclassification attempt carried out according to the predominant (>50%) morphologic component they contained (adenocarcinoma, diffuse infiltrative carcinoma, mucinous carcinoma) and "mixed" carcinoma if none predominated. Cases with unusual morphology were assigned to a "special subtypes" group ("rare" tumors). Correlation of overall survival and staining patterns was carried out. Adenocarcinomas comprised 43.6% (n=51), diffuse infiltrative carcinomas 28.2% (n=33), mucinous carcinomas 6% (n=7), mixed carcinomas 6%, and "rare/other" carcinomas 16.2% (n=19) of the 117 muscle-invasive carcinoma cases. High tumor stage was associated with worse overall survival at multivariate analysis (P=0.000, log-rank). Higher cathepsin E and cyclin-dependent kinase 1 expression was associated with worse overall survival on univariate analysis (log-rank; P=0.050 and 0.001, respectively). Mismatch repair defects were seen in adenocarcinomas and "rare" tumors with MLH1 silencing. These above-mentioned points can lead to the differentiation of metabolic and phenotypic features per gastric carcinoma subtype and may help design targeted approaches.