Immunohistochemical characteristics defined by tissue microarray of hereditary breast cancer not attributable to BRCA1 or BRCA2 mutations: differences from breast carcinomas arising in BRCA1 and BRCA2 mutation carriers.
OBJECTIVE
Most familial breast cancers are not associated with BRCA1 or BRCA2 germ-line mutations. Therefore, it is of major importance to define the morphological, immunohistochemical, and molecular features of this group of tumors to improve genetic testing and also gain further insight into the biological characteristics of tumors.


METHODS
We evaluated the morphological characteristics of 37 tumors arising in women without BRCA1 or BRCA2 mutations, 20 tumors from BRCA1 mutation carriers, and 18 from BRCA2 mutation carriers, all of which were from index patients from breast cancer families. In addition, a tissue microarray was constructed with all tumoral samples to evaluate the immunohistochemical expression of a wide panel of antibodies (11 antibodies) and the amplification of HER-2 and c-MYC genes by fluorescence in situ hybridization. An age-matched group with 50 sporadic breast cancers as controls for non-BRCA1/2 was also included.


RESULTS
Non-BRCA1/2 infiltrating ductal carcinomas (IDCs) showed specific differences from BRCA1 tumors. They were of lower grade (1 and 2); more frequently estrogen receptor, progesterone receptor, BCL2 positive, and p53 negative; had a low proliferation rate (Ki-67 immunostaining < 5%); and did not express P-cadherin. With respect to BRCA2 IDCs and control group, non-BRCA1/2 tumors were of lower grade and had a lower proliferation rate. No cases of HER-2 amplification and/or overexpression were observed except in the control group ( approximately 20%). In contrast, c-MYC amplification was present in 18.2, 62.5, and 12.5% of BRCA1, BRCA2, and non-BRCA1/2 IDCs, respectively, and 31% in the control group.


CONCLUSIONS
This study thus reveals distinct morphological and immunohistochemical features in non-BRCA1/2 and BRCA1 tumors, whereas BRCA2 tumors present characteristics intermediate between the two phenotypes. In addition, the study also demonstrates the usefulness of tissue microarray technology in the evaluation of the immunophenotypic features of hereditary breast cancer.
D000328:Adult; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis; D002277:Carcinoma / Q000235:genetics*; D002455:Cell Division; D005260:Female; D019398:Genes, BRCA1; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010641:Phenotype
D024682:BRCA2 Protein; D015820:Cadherins; D019394:Ki-67 Antigen