HER2/neu expression and amplification in non-small cell lung cancer prior to and after neoadjuvant therapy

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• 作者：Junker ; Klaus ; Stachetzki ; Ulf ; Rademacher ; Daniela ; Linder ; Albert ; Macha ; Hans-Nicol ; Heinecke ; Achim ; et. al.
• 关键词：Non-small cell lung cancer ; Neoadjuvant therapy ; HER2/neu (p185^neu) ; Therapy-induced tumor regression ; Hercep-Test ; FISH
• 刊名：Lung Cancer
• 出版年：2005
• 期刊代码：187_01695002
• 类别：med
• 出版时间：April, 2005
• 卷：48
• 期：1
• 页码：59-67
• 文件大小：324 K

摘要

Summary

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.