PMID- 15777971 OWN - NLM STAT- MEDLINE DCOM- 20050712 LR - 20151119 IS - 0169-5002 (Print) IS - 0169-5002 (Linking) VI - 48 IP - 1 DP - 2005 Apr TI - HER2/neu expression and amplification in non-small cell lung cancer prior to and after neoadjuvant therapy. PG - 59-67 AB - BACKGROUND: Expression and amplification of the HER2/neu protooncogene was analyzed in locally advanced NSCLC in a multimodality therapy approach in order to obtain information on the predictive value of HER2/neu for success or failure of neoadjuvant therapy. METHODS: In the scope of a prospective randomized phase III-trial, tumor tissue of pre-therapeutically obtained mediastinal lymph node biopsies (n=105) and corresponding post-surgical resection specimens (n=44) was analyzed by means of immunohistochemistry (DAKO-Hercep-Test) and fluorescence in situ hybridization (FISH). In 58 of 105 patients with metastatic mediastinal lymph node disease the extent of therapy-induced tumor regression could be established. RESULTS: Concerning HER2/neu expression, 16 lymph node biopsies (15.2%) showed 1+, 2+, or 3+ results. Five of these cases revealed amplification in FISH analysis (4.8%). In 44 corresponding resection specimens, Hercep-Test showed 1+, 2+, or 3+ results in 13 tumors (29.5%). Two of these patients revealed HER2/neu amplification in FISH analysis (4.5%). In patients with HER2/neu expressing tumors a trend towards a less extensive therapy-induced tumor regression could be demonstrated. When comparing pre-therapy and post-surgical results, there was a weak trend towards a selection of HER2/neu expressing tumor tissue in the course of neoadjuvant therapy. CONCLUSIONS: Only a limited subcollective of locally advanced NSCLC meets the biological requirements for anti-HER2/neu therapy. HER2/neu positive tumors appeared to be relatively resistant to chemotherapy and radiation treatment, none of these cases having a pathological complete or at least subtotal response in the corresponding resection specimens. This observation requires confirmation in large randomized controlled studies. FAU - Junker, Klaus AU - Junker K AD - Institute of Pathology, Bergmannsheil-University-Hospital, Burkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany. klaus.junker@ruhr-uni-bochum.de FAU - Stachetzki, Ulf AU - Stachetzki U FAU - Rademacher, Daniela AU - Rademacher D FAU - Linder, Albert AU - Linder A FAU - Macha, Hans-Nicol AU - Macha HN FAU - Heinecke, Achim AU - Heinecke A FAU - Muller, Klaus-Michael AU - Muller KM FAU - Thomas, Michael AU - Thomas M LA - eng PT - Clinical Trial PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20041213 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM CIN - Lung Cancer. 2005 Aug;49(2):279-80. PMID: 16022924 MH - Adult MH - Aged MH - Biomarkers, Tumor/*analysis MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/radiotherapy/surgery MH - Drug Resistance, Neoplasm MH - Female MH - *Gene Amplification MH - *Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - Genes, erbB-2 MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*drug therapy/*genetics/radiotherapy/surgery MH - Male MH - Middle Aged MH - Neoadjuvant Therapy MH - Predictive Value of Tests MH - Receptor, ErbB-2/*biosynthesis MH - Treatment Outcome EDAT- 2005/03/22 09:00 MHDA- 2005/07/13 09:00 CRDT- 2005/03/22 09:00 PHST- 2004/05/06 00:00 [received] PHST- 2004/10/06 00:00 [revised] PHST- 2004/10/12 00:00 [accepted] PHST- 2005/03/22 09:00 [pubmed] PHST- 2005/07/13 09:00 [medline] PHST- 2005/03/22 09:00 [entrez] AID - S0169-5002(04)00535-5 [pii] AID - 10.1016/j.lungcan.2004.10.010 [doi] PST - ppublish SO - Lung Cancer. 2005 Apr;48(1):59-67. doi: 10.1016/j.lungcan.2004.10.010. Epub 2004 Dec 13.