Genetic analysis of BRCA1 and BRCA2 in breast/ovarian cancer families from Aragon (Spain): two novel truncating mutations and a large genomic deletion in BRCA1.

We screened BRCA1 and BRCA2 germline mutations in 60 high-risk breast and/or ovarian cancer patients and 20 relatives from Aragon (Spain) by DHPLC (Denaturing High Performance Liquid Chromatography) and direct sequencing of the entire coding sequence and the splicing sites of both genes. We have identified 17 different pathogenic mutations: 8 in BRCA1 and 9 in BRCA2 in 60 unrelated patients and 50% of relatives were carriers. The prevalence of pathogenic mutations in this study was 33.33%. Two truncating mutations are novel: c.5024_5025delGA in exon 16 of BRCA1 and c.2929delC in exon 11 of BRCA2 (numbered after GenBank U14680 and U43746). Multiplex Ligation Dependent Probe Amplification (MLPA) was performed for large mutational scanning of both genes and a large genomic deletion in BRCA1 was found (DelEx8-13). Furthermore, five mutations are described for the first time in Spanish population: c.1191delC, c.3478_3479delTT and c.6633_6637delCTTAA (BRCA1) and c.3972_3975delTGAG and 3908_3909delTG (BRCA2). Three mutations have been reported previously once in Spain: c.3600_3610del11 (BRCA1), c.5804_5807delTTAA (BRCA2) and c.9246C>A (BRCA2). The mutation c.5374_5377delTATG has been found before only in two unrelated families from Castilla-Leon, Spain (BRCA2). Frequent mutations described in Spanish population have also been present: c.187_188delAG, c.5242C>A and c.5385insC in BRCA1 and c.3492_3493insT and c.9254_9258delATCAT in BRCA2. c.5242C>A, 3972_3975delTGAG and c.5804_5807delTTAA were the recurrent mutations found. Fifteen different unclassified variants were identified (25% families). Although specific BRCA1 and BRCA2 mutations are recurrently reported as a result of genetic founder effects we conclude that heterogeneous ethnicity increases the variety of mutations that can be found in Spanish populations.

Trastornos intestinales funcionales (equivalentes del colon irritable) / Functional bowel disorders (equivalent to irritable bowel syndrome)

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AgNOR evaluation by image processing methods. Staining modifications and results in 126 invasive ductal breast carcinomas.

OBJECTIVE: To analyze cellular proliferating activity in breast cancer by means of a silver (Ag) method (AgNOR) that stains the nucleolar organizer regions (NORs), structures involved in protein transcription. STUDY DESIGN: We analyzed 126 invasive ductal carcinomas and we described: (1) staining modifications aimed at improving the silver method, (2) AgNOR quantitative variables obtained by image processing methods, and (3) the existing relationship between these AgNOR variables and other established breast prognostic factors, such as Scarf-Bloom-Richardson (SBR) grading, tumor size, axillary status, DNA index, and estrogen and progesterone receptors. RESULTS: All quantitative variables based on the AgNOR area showed statistically significant differences with reference to axillary status, tumor size and SBR grading. Cluster analysis based on these variables allowed us to detect two proliferation-level groups of breast carcinoma, one with a low and the other with a high proliferation level. Principal component analysis provided an AgNOR-independent component (first component) unrelated to other prognostic factors. CONCLUSION: Cellular proliferation assessed by AgNOR quantification provides information that may improve prognostic prediction in breast carcinoma.

[Selection criteria used in 1,310 patients in ambulatory major surgery]. / Criterios de selección utilizados en 1.310 pacientes de cirugía mayor ambulatoria.

From October 1990 through March 1992, 1,310 patients underwent surgery on an out-patient basis. Fifty (3.82%) could not be released on the day of surgery, most often because of surgical complications (17), postoperative pain (11), poor screening (9), and nausea and vomiting (8). Screening for out-patient surgery must not be based solely surgical procedure. Factors of social context, personality and associated pathology must also be weighed.