HER2/neu expression and amplification in non-small cell lung cancer prior to and after neoadjuvant therapy.
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.
Junker
Klaus
K
Institute of Pathology, Bergmannsheil-University-Hospital, Bürkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany. klaus.junker@ruhr-uni-bochum.de
Stachetzki
Ulf
U
Rademacher
Daniela
D
Linder
Albert
A
Macha
Hans-Nicol
HN
Heinecke
Achim
A
Müller
Klaus-Michael
KM
Thomas
Michael
M
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D019008:Drug Resistance, Neoplasm; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases