PMID- 16040300 OWN - NLM STAT- MEDLINE DCOM- 20050915 LR - 20220317 IS - 0002-9173 (Print) IS - 0002-9173 (Linking) VI - 124 IP - 2 DP - 2005 Aug TI - Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining. PG - 273-81 AB - 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. FAU - Lewis, Jason T AU - Lewis JT AD - Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. FAU - Ketterling, Rhett P AU - Ketterling RP FAU - Halling, Kevin C AU - Halling KC FAU - Reynolds, Carol AU - Reynolds C FAU - Jenkins, Robert B AU - Jenkins RB FAU - Visscher, Daniel W AU - Visscher DW LA - eng PT - Journal Article PL - England TA - Am J Clin Pathol JT - American journal of clinical pathology JID - 0370470 RN - EC 2.7.10.1 (Receptor, ErbB-3) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Breast Neoplasms/*genetics/metabolism/*pathology MH - Carcinoma, Ductal, Breast/genetics/metabolism/pathology MH - Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology MH - Carcinoma, Lobular/genetics/metabolism/pathology MH - Female MH - *Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Middle Aged MH - Receptor, ErbB-3/*metabolism EDAT- 2005/07/26 09:00 MHDA- 2005/09/16 09:00 CRDT- 2005/07/26 09:00 PHST- 2005/07/26 09:00 [pubmed] PHST- 2005/09/16 09:00 [medline] PHST- 2005/07/26 09:00 [entrez] AID - J9VXABUGKC4Y07DL [pii] AID - 10.1309/J9VX-ABUG-KC4Y-07DL [doi] PST - ppublish SO - Am J Clin Pathol. 2005 Aug;124(2):273-81. doi: 10.1309/J9VX-ABUG-KC4Y-07DL.