Ritterhouse LL, et al. - In a large cohort of carcinomas from diverse anatomic sites, researchers assessed the frequency of SMAD4 (DPC4), a tumor suppressor gene dysregulated in different tumor types, especially pancreaticobiliary and gastrointestinal carcinomas, loss. Immunohistochemistry for SMAD4 has been performed on 1210 carcinomas of tissue microarrays or whole tissue sections of various organs: gastrointestinal tract, liver, pancreas/biliary tract, lung, breast, thyroid, kidney, ovary, and uterus. According to results, SMAD4 loss was observed in 58% of pancreatic adenocarcinomas, 27% of appendiceal adenocarcinomas, 19% of colorectal adenocarcinomas, 16% of cholangiocarcinomas, 10% of lung adenocarcinomas, and <5% of esophageal, breast, gastric and mucinous ovarian adenocarcinomas. The authors concluded that SMAD4 loss is also seen in a small subset of other carcinomas, namely breast, lung, esophageal and gastric adenocarcinomas, in addition to pancreaticobiliary, appendiceal and colonic tumors, all of which are typically positive CK7, similar to pancreaticobiliary carcinomas. Awareness of loss of SMAD4 in these other types of carcinoma is helpful in the assessment of unknown primary site carcinomas.