Cytogenetic heterogeneity and clonal evolution in synchronous bilateral breast carcinomas and their lymph node metastases from a male patient withoutany detectable BRCA2 germline mutation

Two synchronous bilateral breast carcinomas and their matched lymph node me tastases from a 70-year-old man were cytogenetically analyzed. All four tum ors were near-diploid, and except for the primary tumor from the right brea st, had a 45,X,-Y clone in common. The loss of the Y chromosome rr as, howe ver, common to all four tumors, whereas metaphase cells from peripheral blo od lymphocytes showed a normal 46,XY chromosome complement. Th primary tumo r from the right breast rr as monoclonal, with loss of the Y chromosome and gain of Iq, whereas its metastasis had two related clones: the 45,X, -Y cl one, and the other a more complex version of the clone in the primary tumor , with inv(3), -14, and del(16)(q13) as additional changes. The primary tum or from the left breast was poly-clonal with three unrelated clones: 45,X,- Y/45,XY,-18/47,XY,+20, two of which rr ere present in its metastasis. DNA f low cytometric studies show ed diploidy for both primary tumors. No mutatio n in the BRCA2 gene was found on analysis of DNA from peripheral blood lymp hocytes. The present findings show that del(16)(q13) is a recurrent finding among male breast carcinomas and that some of the primary cytogenetic abno rmalities, as well as the pattern of chromosomal changes during the progres sion of sporadic breast carcinoma in the male, are similar to those in the female. In addition, the loss of the Y chromosome in the tumors but not in peripheral blood lymphocytes, suggests a possible role for this abnormality in the pathogenesis of male breast carcinoma. (C) Elsevier Science Inc., 2 000. All rights reserved.