Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA.

Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 (Ppp6c) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of Ppp6c in carcinogenesis, we generated skin keratinocyte-specific Ppp6c conditional knockout mice and performed two-stage skin carcinogenesis analysis. Ppp6c deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1ß was enhanced in Ppp6c-deficient keratinocytes. Overall, we conclude that Ppp6c deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice.

Thymidine phosphorylase expression in human colorectal mucosa, adenoma and carcinoma: role of p53 expression.

The enzyme, thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), which acts as a potent angiogenic factor. The present study immunohistochemically examined the expression of dThdPase in human colorectal mucosa, adenomas and carcinomas, as well as six cultured colorectal carcinoma cell lines, in terms of intratumoral microvessel density (IMVD) and P53 expression. Thymidine phosphorylase was observed in lymphocytes, fibroblasts and macrophages, as well as smooth muscle cells and Schwann cells in the peripheral nerve fibers. The dThdPase-positive stromal cells apparently outnumbered the normal epithelial cells, adenoma and carcinoma cells with dThdPase. Weak but obvious cytoplasmic immunoreactivity was noted in a few normal colonic epithelia, predominantly the upper surface area, while a few adenoma cells showed weak nuclear immunostaining for dThdPase in six (24%) of the 25 colonic adenomas. Expression of dThdPase was noted in 33 (73.3%) of the 45 Dukes A and B, 14 (51.9%) of the 27 Dukes C and 14 (56.0%) of the 25 Dukes D carcinomas. The mean IMVD was 84.0 +/- 26.2 in the 36 dThdPase-negative carcinomas and 97.9 +/- 31.6 in the 61 dThdPase-positive carcinomas, the value being significantly higher in the latter group (P < 0.05). The frequency of dThdPase expression was significantly lower in the P53-negative carcinomas than in the positive carcinomas (P < 0.05). Western blot analysis showed the highest expression of dThdPase in LoVo carrying the wild-type p53 gene, followed by Colo201, Colo320, DLD-11 and WiDr carrying the mutated gene. These results indicate that: (i) the main source of dThdPase is stromal cells, including lymphocytes and macrophages in both colorectal normal and carcinoma tissues; (ii) dThdPase may take part in the induction of intratumoral microvessels, regardless of tumor stage; and (iii) expression might be modulated by not only P53 but also other molecules.

Tubular adenoma with focal squamous metaplasia of the ascending colon.

A case of tubular adenoma with focal squamous metaplasia of the ascending colon in a 66-year-old male is reported. The tumor was a pedunculated polyp with a size of 1.5 X 1.4 X 0.9 cm. Histologically, the tumor showed tubular adenoma with moderate to severe atypia, was accompanied by focal squamous metaplasia. It is thought that squamous epithelial polyp may be derived from colonic adenoma with squamous metaplasia, and that the malignant change of colonic adenoma with squamous metaplasia may lead to squamous cell carcinoma, adenosquamous carcinoma, and mucoepidermoid carcinoma. Only seven cases of colonic adenoma with squamous metaplasia have been reported previously in the literature, and it is yet necessary to discuss the histogenesis, significance, and natural history of colonic adenoma with squamous metaplasia.

Minute mucosal patterns in gastric carcinoma. Magnification radiography of resected gastric specimens.

Magnification radiographs of 32 resected gastric specimens were used for analysis of minute gastric mucosal patterns according to the size and shape of the gastric areas and the appearances of the sulci between them. The mucosal patterns of 92 portions of stomachs were divided into 5 types and observed for correlation with their macroscopic appearances and histology. Destruction of the gastric areas and the sulci was predominant in the carcinomatous mucosa. However, among the patterns of noncarcinomatous mucosa, 18% of those with marked mucosal atrophy had abnormal mucosal patterns impossible to distinguish from carcinomatous mucosa.

Roentgen features of the superficial depressed type of early gastric carcinoma.

The superficial depressed type of early gastric carcinoma is described. The macroscopic appearance is characterized by an irregular erosion, often associated with a deeper central ulceration. The surrounding mucosal folds exhibit abrupt termination, narrowing, and clubbing. The roentgen diagnosis requires good demonstrations of detail. The double-contrast technique is most important and informative and can be used to study almost any part of the stomach.