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Researchers have identified mutations in the BRCA1 gene predisposing women to breast cancer that would not be detected by many tests. Genetic analysis performed on 798 people from families thought to have an increased risk of BRCA1 mutations found that 13% of the women had a mutation that increased their risk of breast cancer. The women had one of 48 different mutations, 24 of which have not been previously reported. Two-thirds of the previously unknown mutations occurred in other parts of the BRCA1 gene than exon 11, which is the part most researchers focus on. Consequently, tests based on exon 11 would miss 33% of the mutations in non-Ashkenazi women., Context.--A mutation in the BRCA1 gene may confer substantial risk for breast and/or ovarian cancer. However, knowledge regarding all possible mutations and the relationship between risk factors and mutations is incomplete. Objectives.--To identify BRCA1 mutations and to determine factors that best predict presence of a deleterious BRCA1 mutation in patients with breast and/or ovarian cancer. Design.--A complete sequence analysis of the BRCA1 coding sequence and flanking intronic regions was performed in 798 women in a collaborative effort involving institutions from the United States, Italy, Germany, Finland, and Switzerland. Participants.--Institutions selected 798 persons representing families (1 person for each family) thought to be at elevated a priori risk of BRCA1 mutation due to potential risk factors, such as multiple cases of breast cancer, early age of breast cancer diagnosis, and cases of ovarian cancer. No participant was from a family in which genetic markers showed linkage to the BRCA1 locus. Major Outcome Measures.--Sequence variants detected in this sample are presented along with analyses designed to determine predictive characteristics of those testing positive for BRCA1 mutations. Results.--In 102 women (12.8%), clearly deleterious mutations were detected. Fifty new genetic alterations were found including 24 deleterious mutations, 24 variants of unknown significance, and 2 rare polymorphisms. In a subset of 71 Ashkenazi Jewish women, only 2 distinct deleterious mutations were found: 185delAG in 17 cases and 5382insC in 7 cases. A bias in prior reports for mutations in exon 11 was revealed. Characteristics of a patient's specific diagnosis (uni-lateral or bilateral breast cancer, with or without ovarian cancer), early age at diagnosis, Ashkenazi Jewish ethnicity, and family history of cancer were positively associated with the probability of her carrying a deleterious BRCA1 mutation. Conclusions.--Using logistic regression analysis, we provide a method for evaluating the probability of a woman's carrying a deleterious BRCA1 mutation for a wide range,of cases, which can be an important tool for clinicians as they incorporate genetic susceptibility testing into their medical practice. JAMA. 1997;278:1242-1250

This article describes the development of a collaborative relationship between a child psychiatry clinic and an adult oncology clinic within a university hospital. The interest of the child psychiatry clinic was to pay attention to children of parents with cancer, and to propose an intervention to support them. A child-centred family counselling model was designed for this purpose. The preparation, implementation, and results of this project are described. Positive results, as well as mistakes and failures are discussed, and recommendations are made regarding this kind of collaboration. [ABSTRACT FROM AUTHOR]

Reports on a random trial to compare irinotecan, a topoisomerase I inhibitor, with supportive care alone for survival, quality of life, and other clinical variables in patients with metastatic colorectal cancer, and for whom fluorouracil has failed. Methods; Findings; Interpretation.

Examines the incidence of warts in patients with systemic lupus erythematosus (SLE). Prevalence of warts in elderly patients; Deficiency in the immune mechanisms of patients with SLE; Inverse correlation between the occurrence of warts and rheumatoid factor activity.

Aim: To examine the expression of thymidylate synthase (TS) and oncoprotein Bcl-2 in advanced colorectal cancer (CRC) patients, and to determine their mutual relationship, association to therapeutic response and impact on disease outcome., Methods: Tumor samples from 67 patients with CRC, who were treated at advanced stage with either irinotecan alone or in combination with 5-fluorouracil/leucovorin, were analyzed for expression of TS and Bcl-2 using immunohistochemistry., Results: A significant linear correlation between lower expression levels of Bcl-2 and lower levels of TS expression was found (P = 0.033). Patients with high levels of both TS and Bcl-2 expression had a significantly longer disease-free survival (DFS) (42.6 mo vs 5.4 mo, n = 25) than those with low TS/Bcl-2 index (P = 0.001). Tumors with low levels of both TS and Bcl-2 were associated with a longer survival with metastasis (WMS) interval in the whole patients group (n = 67, P = 0.035). TS/Bcl-2 index was not significantly related to disease-specific survival., Conclusion: The present data suggest that CRC patients with low TS/Bcl-2 demonstrate a significantly shorter DFS and longer WMS.

Aim: To investigate the changing pattern of beta-catenin expression and its prognostic value in advanced colorectal cancer (CRC)., Methods: Archival tumor samples were analyzed for beta-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC., Results: Membranous beta-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a significant predictor of disease free survival (DFS) (P = 0.023; n = 35), with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045, ANOVA). The other indices were not significant predictors of DFS, and none of the three tested indices (for membranous, cytoplasmic, or nuclear expression) predicted disease-specific survival (DSS). However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046)., Conclusion: Nuclear beta-catenin expression provides additional information in predicting patient outcome in advanced CRC.

Aim: To investigate the changes that occur in E-cadherin expression during the process of metastasis in colorectal cancer., Methods: E-cadherin expression was detected by immunohistochemistry and two indices of expression were calculated which reflected the level of expression and the locations (membrane and cytoplasm). Univariate and multivariate survival analyses were used to assess the value of these two E-cadherin indices as predictors of both disease-free (DFS) and disease-specific (DSS) survival., Results: E-cadherin membrane index (MI), but not cytoplasmic index (CI), was significantly higher in primary tumors than their metastases (P = 0.0001). Furthermore, both primary tumor MI and CI were higher among the patients who developed subsequent metastasis (P = 0.022 and P = 0.007, respectively). Interestingly, both indices were higher in liver metastase compared to other anatomic sites (MI, P = 0.034 and CI, P = 0.022). The CI of the primary tumors was a significant predictor of DFS (P = 0.042, univariate analysis), with a strong inverse correlation between CI and DFS (P = 0.006, multivariate analysis). Finally, the MI of primary tumor proved to be a significant independent predictor of DSS, with higher indices being associated with a more favorable outcome (P = 0.016)., Conclusion: Examination of E-cadherin expression and distribution in colorectal tumors can be extremely valuable in predicting disease recurrence. The observation that aberrant cytoplasmic expression of E-cadherin can predict disease recurrence is obviously of great importance for both patients and clinicians, and significantly affects decisions concerning the therapy and management of the patients.