PMID- 11823970 OWN - NLM STAT- MEDLINE DCOM- 20020221 LR - 20190722 IS - 0046-8177 (Print) IS - 0046-8177 (Linking) VI - 33 IP - 1 DP - 2002 Jan TI - Protein overexpression and gene amplification of c-erbB-2 in breast carcinomas: a comparative study of immunohistochemistry and fluorescence in situ hybridization of formalin-fixed, paraffin-embedded tissues. PG - 21-8 AB - We evaluated 173 consecutive breast carcinomas for c-erbB-2 using a combination of immunohistochemistry (IHC) with a commercial polyclonal antibody (Nitirei) and dual-color fluorescence in situ hybridization (FISH) using the c-erbB-2-specific probe and the chromosome 17 centromere-specific probe from Vysis (Downers Grove, IL) and compared the results with the histologic characteristics of intraductal spread, cancer invasion, and intratumoral heterogeneity. With correction for chromosome 17 copy number, c-erbB-2 amplification was observed in 26 tumors (13.5%): high-level amplification in 23 tumors, and low-level amplification in 3. The gene amplification was positively correlated with c-erbB-2 protein overexpression, defined as 2+ or 3+ immunostaining, on a case-by-case basis (P < .000001). All 3+ immunostaining tumors (19 tumors) showed high-level amplification, although gene amplification was found in only 5 of 27 2+ immunostaining tumors. Although the rates of overexpression and gene amplification did not differ in ductal carcinomas in situ and invasive carcinomas (P = .46 and .53, respectively), they were significantly higher in invasive carcinomas with intraductal spreading (P < .0001). Intratumoral heterogeneity of c-erbB-2 amplification was found in only 1 case; however, in 17 invasive carcinomas, intraductal components expressed c-erbB-2 more intensely than invasive components. We conclude that in breast carcinomas, c-erbB-2 overexpression occurs mostly in tumors with high-level gene amplification, and such overexpression appears to endow carcinoma cells with the capacity for intraductal spreading. The best method for detecting breast carcinomas with c-erbB-2 aberrations using archival tissues is to screen cases by IHC; however, follow-up FISH assays are indispensable for excluding false-positive results. CI - Copyright 2002 by W.B. Saunders Company FAU - Kobayashi, Masako AU - Kobayashi M AD - Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan. FAU - Ooi, Akishi AU - Ooi A FAU - Oda, Yoshio AU - Oda Y FAU - Nakanishi, Isao AU - Nakanishi I LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 1HG84L3525 (Formaldehyde) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Breast Neoplasms/*genetics/metabolism/pathology MH - Carcinoma, Intraductal, Noninfiltrating/*genetics/metabolism/pathology MH - Female MH - Formaldehyde MH - Gene Amplification/*physiology MH - Gene Dosage MH - Genes, erbB-2/*genetics MH - Humans MH - Immunoenzyme Techniques MH - In Situ Hybridization, Fluorescence MH - Middle Aged MH - Paraffin Embedding MH - Receptor, ErbB-2/*biosynthesis MH - Tissue Fixation EDAT- 2002/02/02 10:00 MHDA- 2002/02/22 10:01 CRDT- 2002/02/02 10:00 PHST- 2002/02/02 10:00 [pubmed] PHST- 2002/02/22 10:01 [medline] PHST- 2002/02/02 10:00 [entrez] AID - S0046817702741804 [pii] AID - 10.1053/hupa.2002.30185 [doi] PST - ppublish SO - Hum Pathol. 2002 Jan;33(1):21-8. doi: 10.1053/hupa.2002.30185.