title: Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining.
abstract: Fluorescence in situ hybridization (FISH) and immunohistochemical analysis for assessment of HER-2 status in breast carcinomas are discordant in a significant proportion of cases with equivocal (2+) immunostaining. To evaluate the role of intratumoral heterogeneity and degree of amplification, we performed additional HER-2 immunostains and FISH on tumor-bearing blocks from 20 invasive breast carcinomas with immunohistochemical scores of 2+ with gene amplification and in 18 cases without amplification. Of the amplified cases, 11 (55%) had a 3+ immunohistochemical score on at least 1 additional slide, 8 (40%) remained 2+, and 1 (5%) had a slide scored 1+. All cases rescored 3+ showed high-level amplification in original and repeated FISH; cases remaining 2+ had a heterogeneous FISH profile (low-level amplification or a mosaic mixture of high-level amplified and nonamplified cells) in original and repeated FISH. Of nonamplified cases, 13 (72%) had a 1+ score on at least 1 additional slide, 4 (22%) remained 2+, and 1 (6%) had 1 slide scored 3+. In the nonamplified cases, 17 (94%) showed no amplification in repeated FISH. Significant intratumoral heterogeneity and minimal (low-level) HER-2 amplification account for many breast cancers with 2+ HER-2 protein expression.
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Lewis
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Halling
authors.forename: Carol
authors.initials: C
authors.lastname: Reynolds
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D020893:Receptor, ErbB-3 / Q000378:metabolism*
chemical_list: D020893:Receptor, ErbB-3