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[199] Sporadic Basal-Like Breast Carcinomas Harbour BRCA1 Gene Promoter Methylation and sox2 Overexpression: Similarities with BRCA1-Germ Line Mutated Tumours

SM Rodriguez-Pinilla, D Sarrio, G Moreno-Bueno, Y Rodriguez-Gil, MA Martinez, L Hernandez, D Hardisson, JS Reis-Filho, J Palacios. CNIO, Madrid, Spain; Hospital Universitario 12 de Octubre, Madrid, Spain; Hospital La Paz, Madrid, Spain; Institute of Cancer Research, London, United Kingdom; HHUU Virgen del Rocio, Sevilla, Spain

Background: Tumours arising in BRCA1 mutation carriers and sporadic basal-like breast carcinomas have phenotypic, immunohistochemical and clinical similar charactericts. Since BRCA1 mutations are rarely found in sporadic tumours other epigenetic or genetic mechanisms of BRCA1 inactivation and alterations in other genes implicated in the same pathways have been suggested. SOX2 is an embryonic transcriptor factor located at chromosome 3q, a region frequently gained in BRCA1-germline mutated tumours. The aim of the study was to establish whether BRCA1 and/or FANCF promoter methylation, BRCA1 LOH and sox2 expression were related to basal-like sporadic breast tumours.
Design: 115 sporadic grade 3 tumours including 32 atypical medullary carcinomas (AMC) were immunohistochemically analysed for oestrogen receptor (ER), progesterone receptor (PR), CK8, CK19, CK14, CK5/6, EGFR, HER2, ki67, p53, p-cadherin, vimentin, p63, calponin, caldesmon, CD10, smooth muscle actin, S-100 protein, cdk1, cdk2, cyclin E, cyclin A, cyclin D1, cyclin B1, Rb, survivin, topoisomerase II alpha, p21 and p27 using tissue microarrays. Unsupervised hierarchical cluster was used to defined tumours having basal-like phenotype.
Results: 69 cases (60%) displayed a basal-like phenotype, 31 atypical medullary carcinomas (AMC) and 38 ductal carcinomas. BRCA1 was methylated in 45.7% (27/59) of cases and showed a statistically significant correlation with basal-like phenotype (p=0.028), while FANCF methylation was found in 3 out of 50 cases (2 basal-like and one non-basal-like carcinomas). Sox2 expression was observed in 26.6% of cases and was significantly more frequently expressed in basal-like breast carcinomas (p<0.001).
Conclusions: Our results demonstrate that sporadic basal-like carcinomas frequently harbour BRCA1 gene promoter methylation and share phenotypic characteristics with tumours arising in BRCA1 germline mutation carriers. Sox2 is prefentially expressed in tumours with basal-like phenotype and may play a role in defining their less differentiated/stem cell phenotypic characteristics.
Category: Breast

Monday, March 26, 2007 8:30 AM

Platform Session: Section D, Monday Morning