Assessment of Her-2/Neu status by immunohistochemistry and fluorescence in situ hybridization in mammary Paget disease and underlying carcinoma.
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.
Anderson
Joseph M
JM
Department of Pathology, Rush Medical College, Chicago, Illinois 60612, USA.
Ariga
Reshma
R
Govil
Hema
H
Bloom
Kenneth J
KJ
Francescatti
Darius
D
Reddy
Vijaya B
VB
Gould
Victor E
VE
Gattuso
Paolo
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D010144:Paget's Disease, Mammary / Q000737:chemistry* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis
D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen