Ribonuclease protection assays demonstrated that Brca1 mRNA levels are similar in normal rat mammary glands and mammary carcinomas of various etiologies, including those induced by DMBA, NMU, activated-neu and activated-ras oncogenes.
Our study shows that a low expression of bcl-2 characterises most Brca1 -associated breast carcinomas, a biological trait which seems not to be shared by Brca2 -associated tumours nor to be related to oestrogen receptor and/or p53 status. bcl-2 might thus be one of the target genes involved in the oncogenesis related to Brca1 and its down-regulation may account for the increased apoptosis and the high proliferative rate observed in Brca1 -associated carcinomas.
Loss of the wild-type BRCA1 allele was observed in 3/3 breast tissues (2 breast carcinomas and 1 ductal carcinoma in situ) but in 0/6 colorectal tissues (5 carcinomas and 1 adenoma), suggesting that BRCA1 loss is not critical for colorectal tumorigenesis.
Twenty-seven individuals with invasive carcinomas were found to have mutations (14 with 185delAG and one with 5382insC in BRCA1 and 12 with 6174delT in BRCA2).
In BRCA1-BC's, pS2 was expressed in only 10/33 (30.3%) carcinomas, and 4/4 (100%) ER positive: among sporadic carcinomas, 133/193 (68.9%) cases were pS2-positive, 102/127(80.37%) ER positive; the difference was significant (p<0.0001).
The aim of this analysis is to investigate the clinical and pathological features of these BRCA1 associated carcinomas as compared to other breast cancers in this representative sample.
Analysis of chromosome 17 DNA markers in the five family members tested show that three individuals affected by both NF1 and carcinomas share a common haplotype including the NF1 and BRCA1 loci on chromosome 17.
DNA extracted from paraffin wax blocks of 36 BRCA1 associated ovarian and fallopian tube carcinomas was analysed by LOH polymerase chain reaction using seven highly polymorphic microsatellite markers spanning chromosome 13q.
These data indicate that HMGA1 proteins are involved in transcriptional regulation of the BRCA1 gene, and their overexpression may have a role in BRCA1 downregulation observed in aggressive mammary carcinomas.
These data suggest that the imaging findings of BRCA1 and BRCA2-associated carcinomas differ from each other and from age-matched cases of sporadic breast carcinoma.
Over 90% of peritoneal cancer in patients from HBOC syndrome kindreds and associated with BRCA1 and BRCA2 mutations are serous carcinomas, which is equivalent with the proportion of ovarian cancers that are serous carcinomas in similar patients.
Current data indicate that each of these histologic subtypes is associated with distinct morphologic and molecular genetic alterations: high-grade serous and possibly endometrioid carcinomas most probably arise from surface epithelial inclusion glands with TP53 mutations and dysfunction of BRCA1 and/or BRCA2; low-grade serous carcinomas probably arise in a stepwise fashion in an adenoma-borderline tumor-carcinoma sequence from typical to micropapillary borderline tumors to low-grade invasive serous carcinoma via activation of the RAS-RAF signaling pathway secondary to mutations in KRAS and BRAF; mucinous carcinomas arise via an adenoma-borderline tumor-carcinoma sequence with mutations in KRAS; low-grade endometrioid carcinomas arise from endometriosis via mutations in CTNNB1 (the gene encoding beta-catenin) and PTEN.
Unsupervised cluster data analysis of both hereditary and sporadic cases using the complete set of immunohistochemical markers demonstrated that most BRCA1-associated carcinomas grouped in a branch of ER-, HER2-negative tumors that expressed basal cell markers and/or p53 and had higher expression of activated caspase 3.
In this study, the relationships between GADD45, ZBRK1, and BRCA1 expression were investigated in colon carcinomas. mRNA expression of these three genes was analysed in 116 colon carcinomas by real-time reverse transcriptase polymerase chain reaction (RT-PCR).
Somatic mutations in the BRCA genes are rarely found in hereditary tumors; by contrast, BRCA1 and BRCA2 loss of heterozygosity (LOH) is found in almost all BRCA1 and BRCA2 carcinomas, respectively.
Approximately 6% of BRCA1 carriers and 2% of BRCA2 carriers who undergo prophylactic salpingo-oophorectomy will be found to have occult carcinomas if the ovaries and tubes are rigorously examined.
Since myoepithelial markers are frequently expressed in breast carcinomas with a basal-like phenotype, which are frequently occurring tumors in women with BRCA1 germline mutations, we evaluated whether CAV1 was associated with a basal-like phenotype in 509 sporadic and 47 hereditary BRCA1-/BRCA2-associated carcinomas.
Six clinically occult primary gynecologic malignancies (2 stage IIIC serous carcinomas of the ovary, 3 in situ serous carcinomas of the fallopian tube, and 1 stage IIB invasive serous carcinoma of the fallopian tube) and 1 occult ovarian metastasis from breast carcinoma were identified in the PO specimens of 7 women (all BRCA1 mutated).
The tubal fimbria is a common site of origin for early (tubal intraepithelial carcinoma or TIC) serous carcinomas in women with familial BRCA1 or 2 mutations (BRCA+).
Given the high prevalence of MYC amplification in tumours of BRCA1 mutation carriers and the similarities between these and sporadic "basal-like" carcinomas, the prevalence of MYC amplification in "basal-like" breast carcinomas was investigated.