Expression of Tumor Suppressor and Tumor-related Proteins in Differentiated Carcinoma, Undifferentiated Carcinoma with Tubular Component and Pure Undifferentiated Carcinoma of the Stomach

Abstract

The recent development of tissue microarray (TMA) technology allows high-throughput protein expression profiling of cancer tissues by immunohistochemistry. We attempted to clarify the derivation of undifferentiated-type gastric carcinoma with tubular component by using TMA. We constructed a TMA system composed of six paraffin blocks in which 274 samples of formalin-fixed gastric carcinoma tissue from 274 patients were embedded. Using this system, we performed immunohistochemical stains for five tumor suppressor and tumor-related proteins, i.e. p53, p16, hMLH1, c-erbB-2 and carcinoembryonic antigen (CEA). The 274 gastric carcinomas were histopathologically divided into the following three groups according to the degree of differentiation: differentiated-type (D-type), undifferentiated-type with tubular component (UT-type) and pure undifferentiated-type (UP-type). Immunohistochemical results were then compared with histological types. The percentages of abnormal expression of each protein in D-type, UT-type and UP-type carcinomas were as follows: 27% (38/143), 17% (17/98) and 15% (5/33) for p53; 27% (39/143), 19% (19/98) and 18% (6/33) for p16; 38% (54/143), 44% (43/98) and 24% (8/33) for hMLH1; 15% (22/143), 5% (5/98) and 0% (0/33) for c-erbB-2; and 22% (31/143), 35% (34/98) and 70% (23/33) for CEA. UP-type carcinomas exhibited the lowest frequencies of abnormal expression for p53, p16, hMLH1 and c-erbB-2, but the highest frequencies for CEA. UT-type carcinomas generally showed intermediate frequencies between those of D-type and UP-type carcinomas. Differences between D-type and UP-type for c-erbB-2 (P < 0.05) and CEA (P < 0.001) were significant, as were differences between D-type and UT-type for c-erbB-2 (P < 0.05) and CEA (P < 0.05), and differences between UT-type and UP-type for hMLH1 (P < 0.05) and CEA (P < 0.001). These findings reveal that gastric carcinomas have distinct expression profiles for tumor suppressor and tumor-related proteins depending on histological types, and support the hypothesis that UT-type carcinomas are derived not only from D-type but also from UP-type carcinomas. We also found significant differences between abnormal protein expression and other clinicopathological parameters such as gender, age and status of tumor and nodes.