Phenotypic alteration in malignant transformation of colonic villous tumours: with special reference to a comparison with tubular tumours.

AIMS: To clarify the cellular differentiation of colorectal villous tumours in malignant transformation, compared with that of tubular tumours (tubular adenoma and adenocarcinoma arising in tubular adenoma). METHODS AND RESULTS: Forty-nine cases of colorectal villous tumours [six cases of low-grade villous adenoma, 21 of high-grade villous adenoma (VA), nine of invasive carcinoma in villous adenoma (CIVA), and 13 of pure villous carcinoma (PVC)] and 46 cases of tubular tumours [14 cases of low-grade and 17 of high-grade tubular adenoma (TA), and 15 cases of carcinoma in tubular adenoma (CITA)] were selected for this study based on their expression patterns of CD10 (small intestinal brush border), MUC2 (intestinal goblet cell), and HGM (gastric foveolar epithelium). HGM was more frequently expressed in the adenomatous components of villous tumours (63%) than in those of tubular tumours (14%) (P < 0.05). CD10 expression of high-grade TAs (47%) and carcinomas arising in TA (60%) was significantly higher than that of villous tumours (0%) (P < 0.05). CONCLUSIONS: There were significant differences in the phenotypic expression of adenoma and adenocarcinoma between villous and tubular tumours, respectively. Villous tumours have a pathway of malignant transformation different from that of tubular tumours. Because of biological differences, colorectal villous tumours should be distinguished from tubular neoplasia. The analysis of the phenotype of colorectal neoplasms is useful for the evaluation of tumour progression.

Phenotypical characteristics of undifferentiated carcinoma of the pancreas: a comparison with pancreatic ductal adenocarcinoma and relevance of E-cadherin, alpha catenin and beta catenin expression.

The characteristics of undifferentiated (anaplastic) carcinoma (UC) of the pancreas were analysed and compared with those of poorly differentiated adenocarcinoma (PA). Eight cases of UC of the pancreas were evaluated by clinicopathological and immunohistochemical methods and compared with 20 cases of PA. Large size of the tumor, local invasion and lymph node metastasis were frequently seen in UC, leading to a significantly worse prognosis compared to that of PA (p=0.022). Immunohistochemically, E-cadherin expression was completely lost in 7/8 UC cases, whereas half the PA cases revealed a strong reactivity for E-cadherin. alpha- and beta-catenin expressions tended to be impaired in UC compared with PA. The results suggest that the altered expression of adhesion molecules is correlated with dedifferentiated change and is contributory to its aggressive biological behaviour.

Multiple 'serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation.

A 70-year-old woman underwent right hemicolectomy and six carcinomas were recognized in the resected colon. These carcinomas were considered to be of a cell lineage common to serrated adenoma (SA) and hyperplastic (metaplastic) polyp (H/MP), because of the occurrence of multiple SAs and H/MPs around the carcinomas, as well as the co-existence of SA and H/MP areas within the carcinomas. These carcinomas had the following common histological and immunohistochemical features: a serrated structure resembling SA; a lace-like structure; infiltrative growth within the muscularis propria, with dedifferentiation at the invasive front; and immunohistochemical expression of pS2 and human gastric mucin. Based on these features, a new subtype of carcinoma is proposed, with a cell lineage common to SA and H/MP. It would also seem that p53 is involved in the serrated adenoma-carcinoma sequence.

Reconstitution of an efficient protein translocation machinery comprising SecA and the three membrane proteins, SecY, SecE, and SecG (p12).

A cytoplasmic membrane protein, p12, of Escherichia coli was discovered as a new factor that stimulates the protein translocation activity reconstituted with SecA, SecY, and SecE (Nishiyama, K., Mizushima, S., and Tokuda, H. (1993) EMBO J. 12, 3409-3415). Direct involvement of p12 in protein translocation was subsequently demonstrated in vivo by genetic studies, and the name SecG has been proposed for p12 (Nishiyama, K., Hanada, M., and Tokuda, H. (1994) EMBO J. 13, 3272-3277). To elucidate the role of SecG in protein translocation and to characterize the translocation apparatus comprising these four Sec proteins, the activity of reconstituted proteoliposomes was examined in detail as a function of the amount of each component. SecG markedly stimulated the translocation activity over wide ranges of amounts of the other three Sec proteins, indicating that none of the other three Sec proteins substitutes for the SecG function. Detailed kinetic analyses indicated that the activity of proteoliposomes was dependent on the amount of the SecY-SecE complex when SecG was absent and the amount of the SecY.SecE.SecG complex when the proteoliposomes contained SecG. The translocation activity of the latter complex was significantly higher than that of the former one. Binding of SecA to liposomes appreciably increased when they contained both SecY and SecE, whereas the further presence of SecG did not enhance the binding. On the other hand, the ATPase activity of SecA, which was dependent on proOmpA and SecY.SecE-containing proteoliposomes, was significantly enhanced when the proteoliposomes contained SecG. Taken together, these results indicate that SecG enhances the translocation activity of the apparatus after the step of SecA targeting to SecY.SecE.