HER-2/Neu overexpression is seen in 20% to 30% of invasive
breast carcinomas and has been reported in as many as 80% of high-grade infiltrating
carcinomas. Earlier studies have suggested that 100% of the
tumor cells in
mammary Paget disease show overexpression of HER-2
protein. We undertook this study to assess HER-2 status of
mammary Paget disease and of the underlying
breast carcinoma, when present, by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
Formalin-fixed,
paraffin-embedded tissue from 20 cases of
mammary Paget disease were analyzed for HER-2 status by IHC and FISH. IHC for
estrogen receptor (ER) was also performed. The patients ranged in age from 34 to 88 years, with a mean age of 62 years. Eighty percent of the cases showed strong overexpression (3+) of HER-2
protein by IHC, and all of these cases showed more than 5-fold amplification of the HER-2 gene by FISH. The remaining 4 cases, which were negative for HER-2/Neu by IHC, showed no amplification by FISH. All of the latter cases expressed ER, whereas no case that overexpressed HER-2 expressed ER. Sixteen cases had an underlying
tumor, which was in situ in 6 cases. The underlying
tumors were identical to the Paget disease with respect to their HER-2/Neu overexpression by both IHC and FISH. HER-2 overexpression was identified in 80% of our cases of Paget disease. There was 100% concordance between HER-2
protein overexpression by immunohistochemistry and gene amplification in both the Paget and the underlying
tumor. Moreover, all of the cases negative for HER-2 overexpression expressed ER, whereas those positive for HER-2 did not.