The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

Osin, Pinchas; Lakhani, Sunil R.

doi:10.1186/bcr11

Cited by 58 publications

(32 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Between 63 and 90% of BRCA1 carcinomas have been reported to be ER negative in different series (Lynch et al, 1998;Osin et al, 1998;Armes et al, 1999;Eisinger et al, 1999;Noguchi et al, 1999;Osin and Lakhani, 1999;Lakhani et al, 2002;Palacios et al, 2003;Robson et al, 2004;Foulkes et al, 2004b;Eerola et al, 2005a;Oldenburg et al, 2006). This percentage is higher than that found in age-and grade-matched sporadic counterparts (Palacios et al, 2003;Foulkes et al, 2004b).…”

Section: Hormone Receptorscontrasting

confidence: 45%

Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations

et al. 2006

View full text Add to dashboard Cite

Tumors arising in BRCA1 and BRCA2 mutation carriers appear to have specific pathological and gene expression profiles, which show a high level of concordance. BRCA1 tumors are high-grade, negative for hormone receptors, have a high proliferation rate, and are positive for some cell cycle promoter genes. BRCA2 tumors present a phenotype opposite to BRCA1 tumors but very similar to sporadic tumors, except that BRCA2 overexpress some DNA repair markers such as CHEK2, show high cytoplasmic expression of RAD51, and are negative for HER-2 amplification and expression. Some of these characteristics have also been found in cDNA expression studies, although more analysis are necessary in order to obtain new markers that can be associated with a germ line mutation in BRCA1 or BRCA2. In this way, some studies in normal tissues of BRCA1/2 carriers suggest that differences exist in the level of expression of some genes when compared with noncarriers. Finally, IHC studies in tumors carrying a mutation in CHEK2 are rare and show contradictory results, probably due to the low number of these cases. However, they represent an example showing how different mutations of the same gene may be associated with specific histological subtypes of cancer.

show abstract

Section: Hormone Receptorscontrasting

confidence: 45%

Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations

et al. 2006

View full text Add to dashboard Cite

show abstract

“…25,34,35,[37][38][39][40][41] Between 73 and 90% of BRCA1 carcinomas were estrogen receptor-negative in different series. 34,35,38 For example, Lakhani et al 25 reported that 90% of BRCA1-related breast cancers were estrogen receptor-negative compared with 35% in controls.…”

Section: Familial Breast Cancer Characteristicsmentioning

confidence: 99%

“…However, hereditary breast cancer studies are uncommon and generally limited to the analysis of the expression of individual cell-cycle proteins. 38,40,41,67 The expression of cyclin D1 has been reported in some series, but there is little information available for most of the other cell-cycle markers. 38,41,67 Most series have exhibited lower cyclin-D1 expression levels in BRCA1 than in sporadic tumors.…”

Section: Alterations In Cell-cycle Regulationmentioning

confidence: 99%

“…38,40,41,67 The expression of cyclin D1 has been reported in some series, but there is little information available for most of the other cell-cycle markers. 38,41,67 Most series have exhibited lower cyclin-D1 expression levels in BRCA1 than in sporadic tumors. 38,40,68 Cyclin-D1 expression in BRCA2 tumors has been found at an intermediate level between those of BRCA1 and sporadic tumors.…”

Section: Alterations In Cell-cycle Regulationmentioning

confidence: 99%

See 1 more Smart Citation

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications

2005

View full text Add to dashboard Cite

Cancer arising in carriers of mutations in the BRCA1 and BRCA2 genes differs from sporadic breast cancer of age-matched controls and from non-BRCA1/2 familial breast carcinomas in its morphological, immunophenotypic and molecular characteristics. Most BRCA1 carcinomas have the basal cell phenotype, a subtype of highgrade, highly proliferating, estrogen receptor-and HER2-negative breast carcinomas, characterized by the expression of basal or myoepithelial markers such as basal keratins, P-cadherin, epidermal growth factor receptor, etc. This phenotype is rarely found in BRCA2 carcinomas, which are of higher grade than sporadic age-matched controls, but tend to be estrogen receptor-and progesterone receptor-positive. The expression of the cell-cycle proteins cyclins A, B1 and E and SKP2 is associated with a BRCA1 phenotype, whereas cyclin D1 and p27 expression is associated with BRCA2 carcinomas. Recent studies have shown that hereditary carcinomas that are not attributable to BRCA1/2 mutations have phenotypic similarities to BRCA2 tumors, but tend to be of lower grade and proliferation index. 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. Furthermore, all types of hereditary breast carcinomas have a low frequency of HER2 expression. Finally, comparative genomic hybridization studies have revealed differences in chromosomal gains and losses between genotypes. The pathological and molecular features of hereditary breast cancer can drive specific treatments and influence the process of mutation screening. In addition, detecting molecular changes such as BRCA1/2 LOH in nonatypical cells obtained by random fine-needle aspiration, ductal lavage or nipple aspirate fluid may help to earlier identify carrier women who are at an even higher risk of developing breast carcinoma. Keywords: hereditary breast cancer; BRCA1; BRCA2; molecular pathology; histopathology; immunohistochemistry It is currently estimated that 5-10% of all breast cancers are hereditary and attributable to mutations in high-penetrance susceptibility genes, but only two of these have been identified: BRCA1 (OMIM 113705) 1 and BRCA2 (OMIM 600185). 2 BRCA1 mutations are associated with families with breast and ovarian cancer, while families with male breast tumors are associated with mutations in the BRCA2 gene.While early estimates suggested that BRCA1 and BRCA2 mutations were responsible for 75% of multiple-case breast cancer families and for the majority of families with multiple breast and ovarian cancers, 3,4 recent data have shown that these percentages may have been overestimated. In fact, the percentage of high-risk families associated with mutations in these genes seems to be around 25% in all series investigated, including the Spanish population. 5 Mutations are found in a high percentage (about 45%) of families with breast and ovarian tumors, while the mutation rate in families with only breast can...

show abstract

“…Tipicamente são carcinomas pouco diferenciados, apresentam elevado grau nuclear e alta taxa proliferativa. Além disso, geralmente são negativos para receptores de estrógeno e c-erbB-2, mas positivos para o p53 (10) . Embora mutações no BRCA1 sejam raras nos carcinomas mamários esporádicos, a perda de expressão do RNA mensageiro e da proteína codificada pelo BRCA1 é freqüente nos carcinomas não-familiares, provavelmente devido a fatores epigenéticos (8,18,19) .…”

Section: Introductionunclassified

Impacto prognóstico da expressão imuno-histoquímica do BRCA1 nos carcinomas mamários esporádicos

Ribeiro‐Silva

Garcia

Chahud³

et al. 2005

J. Bras. Patol. Med. Lab.

View full text Add to dashboard Cite

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

Cited by 58 publications

References 28 publications

Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations

Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications

Impacto prognóstico da expressão imuno-histoquímica do BRCA1 nos carcinomas mamários esporádicos

Contact Info

Product

Resources

About