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Hum Pathol. 2003 Dec;34(12):1299-305.

Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry.

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Institute of Pathology, Heinrich-Heine-University, Düsseldorf, Germany.


Secretory carcinomas (SCA) are distinguished from infiltrating ductal carcinomas (IDC) of the breast by their characteristic histomorphology and more favorable prognosis and by the expression of a chimeric tyrosine kinase that is encoded by the ETV6-NTRK3 fusion gene. On this basis, we evaluated 13 SCAs (12 of them with ETV6-NTRK3 gene fusion) by molecular and immunohistochemical (IHC) methods. DNA was obtained from 8 of 13 microdissected SCAs and was analyzed for genetic alterations (GA) by comparative genomic hybridization (CGH). IHC staining was performed for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67 (MIB1) in all 13 cases. Molecular and immunohistochemical results in SCAs were compared with previous data regarding immunohistochemical and molecular characteristics of IDCs. An average of 2.0 GAs (range: 0 to 6) were detected, including recurrent gains of chromosome 8q (37.5%) and 1q (25%) and losses of 22q (25%). Four of 13 (31%) SCAs were positive for ER, and 2 were positive for PR. The mean MIB1-labeling index was 11.4% (range: <1 to 34%). Her-2/neu protein overexpression was detected in 2 cases, including 1 with strong (score 3+) and 1 with weak HER2/neu expression (score 2+). Fluorescence in situ hybridization analysis of the latter case showed no evidence of HER-2/neu-gene amplification. Compared with previous findings in IDCs, SCAs are characterized by a relatively low number of GAs, a low proliferative rate, infrequent HER2/neu protein overexpression, decreased steroid hormone receptor expression, and expression of ETV6-NTRK3 fusion gene. These results support the hypothesis that SCAs have immunohistochemical and genetic features that distinguish them from IDCs of the usual type.

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