APC genotype is not a prognostic factor in familial adenomatous polyposis patients with colorectal cancer.

PURPOSE: Several studies have shown that the clinical phenotype of patients with familial adenomatous polyposis is influenced by the position of the associated germline mutation in the APC gene. The aim of this work was to assess whether the site of the APC mutation may also predict the survival of familial adenomatous polyposis patients with a confirmed diagnosis of colorectal cancer. METHODS: A total of 387 familial adenomatous polyposis patients with colorectal cancer were examined. Of these, 287 (74 percent) belonged to families with an identified mutation, whereas 100 (26 percent) were from families in which no detectable APC mutation had been found by standard screening methods. The subjects were subdivided into four groups, according to the presence and localization of the identified mutation: with mutation before (a), at (b), or beyond codon 1309 (c), and without identified mutation (d). RESULTS: The cumulative five-year survival estimate of all cases included in the study was 0.56 (95 percent confidence interval, 0.51-0.61). No difference was observed in survival probability among patients from families with mutations before (0.56; 95 percent confidence interval, 0.49-0.63), at (0.58; 95 percent confidence interval, 0.43-0.72), or beyond (0.52; 95 percent confidence interval, 0.31-0.73) codon 1309 or those from families that were mutation negative (0.58; 95 percent confidence interval, 0.48-0.68) (log-rank test, P = 0.9). Survival analysis did not reveal any significant advantage for patients carrying a mutation in a specific region of the APC gene, after adjustment for age, gender, site, and stage. CONCLUSION: These data do not support the hypothesis that APC mutation may influence the outcome of familial adenomatous polyposis cases affected by colorectal cancer.

Atypical epithelial proliferation in fallopian tubes in prophylactic salpingo-oophorectomy specimens from BRCA1 and BRCA2 germline mutation carriers.

Although growing numbers of tubal carcinomas in carriers of BRCA1 and BRCA2 germline mutations have been reported, very little is known about the nature and frequency of their possible precursor lesions. The aim of this study is to investigate the occurrence of atypical proliferative tubal lesions in grossly normal fallopian tubes from 26 women with BRCA1 and BRCA2 germline mutations who underwent prophylactic salpingo-oophorectomy and whose ovaries were histologically negative for carcinoma. Fallopian tubes from 49 women who had undergone hysterectomy with salpingo-oophorectomy for uterine leiomyoma served as controls. In the 22 BRCA1-mutated women, there were two in situ carcinomas and two atypical hyperplasias of the tubal epithelium. The tubes of the BRCA2-mutated women and of the 49 control women did not show any atypical proliferation. The frequency of proliferative lesions of the tubal epithelium, including in situ carcinoma, appears to be increased in BRCA1 mutation carriers. Removal and thorough examination of the fallopian tubes at the time of surgical prophylaxis for ovarian cancer is therefore recommended.

Different expressivity of BRCA1 and BRCA2: analysis of 179 Italian pedigrees with identified mutation.

Mutations in BRCA1 and BRCA2 show different expressivity with respect to cancer risk, and allelic heterogeneity may be present in both genes. We collected 179 pedigrees with identified germline mutation (104 BRCA1 and 75 BRCA2), ascertained in six collaborating centers of the Italian Consortium for Hereditary Breast and Ovarian Cancer. Significant heterogeneity was detected for several variables, and a logistic regression model including age of diagnosis in the proband, presence of ovarian cancer in the family, presence of prostate or pancreatic cancer in the family, and presence of male breast cancer in the family proved to be effective in predicting the presence of a mutation in a gene rather than the other. Excess of familial aggregation of both breast and ovarian cancer was observed in both genes. Proportion of ovarian cancer was increased in the 5' portion of BRCA1, and presence of prostate or pancreatic cancer in a family was correlated with presence of ovarian cancer in BRCA2.