Overexpression of p53 protein correlates with a high risk of malignant transformation of adenomas in patients with multiple colorectal adenomas

To assess the correlation of p53 oncoprotein expression with the high risk of developing carcinomas in patients with multiple colorectal adenomas, 25 cases with histologic carcinoma in adenoma (CIA) were examined by immunohistochemistry using a monoclonal antibody specific to human p53 protein (wild and mutant). The 25 cases were classlfied into multiple and single groups. The former contained 13 cases with synchronous multiple colorectal adenomas (one to six adenomas) and adenocarcinoma. The latter included 12 cases with single CIA only. This study revealed an overall incidence of 57.14% of p53 overexpression in carcinomatous lesions and 31.9% in adenomatous lesions, which was statistically significant ( P <0.05). The carcinomatous lesions showed a diffuse staining pattern, whereas the adenomatous lesions showed a focal pattern. A significant finding was that the incidence of p53 overexpression was slgnificantly higher in multiple groups (81.25%) than in single groups (31.43%) in the carcinomatous ( P <0.01) rather than in the adenomatous ( P >0.05) lesions. There were no correlations between p53 overexpression and proliferation activity or carcinoembryonic antigen expression. The results indicate that p53 abnormality may be an important genetic factor responsible for the high risk of developing carcinomas in patients with multiple adenomas.     

Expression and somatic mutation on androgen receptor gene in prostate cancer

BACKGROUND: Lack of androgen receptor (AR) expression or mutation on the AR gene creates the tendency for androgen independence and progression of prostate cancer. However, the association between the progression and AR expression or mutations is still controversial. In this study, we evaluated the prognostic significance of AR expression and mutations in prostate cancers. METHODS: Forty-two prostate adenocarcinomas and three lymph node metastatic lesions sampled prior to hormonal therapy were included in this study; AR expression was analyzed immunohistochemically using an antibody against AR and the result was scored as the percentage of AR-positive tumor cells in the total tumor cells. Polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing were used to detect AR mutations. RESULTS: Our study revealed the average AR expression in the prostate adenocarcinoma was 52.2 +/- 27.1%, which was significantly lower than that in the adjacent non-tumorous prostate tissue (68.3 +/- 18.3% in average) (P < 0.001). A significant correlation was obtained between progression-free survival and AR expression (P < 0.01). By SSCP analysis, three silent mutations (T649T, E709E and E711E) were detected in three separate prostate carcinomas. CONCLUSION: : We conclude that AR expression is a useful prognostic indicator for tumor progression. Androgen receptor mutation may be an uncommon molecular event in untreated prostate cancer in Japanese men.     

Extensive intraductal component (EIC) and estrogen receptor (ER) status in breast cancer

The extensive intraductal component (EIC) of primary breast carcinoma is a special spread pattern observed In the breast. Extensive intradwtal component may extend diffusely over the entim breast. Therefore, EIC Is considered to be an important risk factor for local recurrence in breast-conserving therapy. However, the pathogenesis of EIC remains uncertain. Whether or not the estrogen receptor (ER) has an influence on its biologic behavior has not been fully studied. A consecutive series of 142 breast carcinomas submitted to the pathology department were examined on step gross dons of 5.0 mm thick. Extensive intraductal component was determined and divided into three types. Estrogen receptor was examined using both immunohistochemistry (ER-IHC) and enzyme immunoassay (ER-EIA). Extensive intraductal component was found In 78 of 138 (56.52%) invaslve carcinomas including invasive ductal carcinoma with a predominant intraductal component. Estrogen receptor-IHC positivity was 42.96% (61/142) in the Invasive breast carcinoma. Estrogen receptor positivity showed no significant difference between ElC-positive and -negative cases, as well as between EIC and Invasive main tumor in the ElC-positive cases. But within the ElC-positive group, ER positivity was found to be higher in the peripheral type of ElC-II and ElC-III than in the central type of ElC-I ( P <0.05). Although ER may not play an essential role in the pathogenesis of EIC, it has shown some significance in the development of peripheral type EIC because of its higher presence in the peripheral type of EIC-II and EIC-III than in the central type of EIC-I.