Toshihiro Kai

Clinicopathological characteristics of colorectal cancers with loss of imprinting of insulin-like growth factor 2

Loss of imprinting (LOI), the biallelic expression of an imprinting gene, of insulin‐like growth factor 2 (IGF2) has been reported to be associated with colorectal carcinogenesis because of its high prevalence in normal colorectal mucosa as well as cancerous tissue in patients with colorectal cancer. However, the characteristics of colorectal cancer associated with IGF2 LOI have not been clearly demonstrated. In this study, we investigated the IGF2 LOI status of tumor and normal mucosa in 255 consecutive patients with colorectal cancer. Of these, 95 were informative for IGF2 LOI, by direct sequencing of mRNA of IGF2. Regarding the LOI status in each patient, the prevalence of LOI in nontumorus normal mucosa was significantly higher in cases with LOI‐positive cancer than in those with LOI‐negative cancer (p < 0.001). Concerning the clinicopathological characteristics of LOI‐positive cancer, the prevalence of poorly differentiated or mucinous carcinoma (p = 0.016) and of right‐sided locations (p = 0.009) were significantly higher than those of LOI‐negative cancer. Contrary to past reports that revealed a significant correlation between microsatellite instability (MSI) and IGF2 LOI in a relatively small series of noncohort patients, our study did not find a statistically significant difference in LOI‐positive rate between MSI‐positive and ‐negative cases. Our results suggested the presence of a particular type of colorectal cancer associated with the proximal colon and poor differentiation, but independent of MSI. These results may contribute to clarification of the mechanism of colorectal tumorigenesis and to determining an appropriate screening strategy for colorectal carcinoma.

Distribution of Transforming Growth Factor‐β and Its Receptors in Gastric Carcinoma Tissue

The distribution of the three mammalian isoforms of transforming growth factor (TGF)‐β (TGF‐β1,‐β2, and ‐β3) as well as their signaling receptors, TGF‐β type I and type II receptors (TβR‐I and TβR‐II, respectively), in gastric carcinoma tissue was examined by immunohistochemistry using specific antibodies. Tissue specimens were obtained from 25 cases of gastric carcinoma, which were classified into two groups according to Laurens classification, i.e. 15 cases of diffuse carcinoma and 10 cases of intestinal carcinoma. In normal gastric mucosa apart from carcinoma nests, all of TGF‐β1, ‐β2, ‐β3, TβR‐I and TβR‐II were clearly demonstrated in fundic glands. In sharp contrast, none of them was detectable in surface mucous cells. In carcinoma cells, strong staining for TGF‐β1, ‐β2 and β3 was obtained only in diffuse‐type carcinoma. In particular, carcinoma cells scattered as single cells or small nests had a tendency to show strong staining for TGF‐βs. The receptors tended to be distributed concomitantly with the ligands, and diffuse‐type carcinoma showed stronger receptor staining than intestinal‐type carcinoma. In cancer stroma, TGF‐βs and receptors were detected in both diffuse and intestinal types, but the area with positive staining was wider and more dispersed in diffuse‐type carcinoma than in intestinal carcinoma. These results suggest that TGF‐β may contribute in part to the variety of histogenesis and mode of progression of gastric carcinoma.