AQUA and FISH analysis of HER-2/neu expression and amplification in a small cell lung carcinoma tissue microarray.
OBJECTIVE
Most small cell lung carcinoma (SCLC) patients have metastatic disease at the time of diagnosis and are faced with poor prognosis and limited treatment options. Reports of HER-2/neu gene amplification and overexpression in this malignancy have raised the possibility of applying targeted immunotherapy with trastuzumab, the monoclonal antibody used to treat metastatic breast cancer. However, a review of the studies measuring HER-2/neu gene amplification and protein expression in SCLC reveals discordant results. The aim of the present study was to re-examine HER-2/neu expression in SCLC in relation to gene copy number using the new, highly sensitive, immunofluorescence automated quantitative analysis (AQUA) technology.


RESULTS
Fluorescence in situ hybridization (FISH) was used to measure HER-2/neu gene copy number and amplification status and AQUA was used to measure protein expression in a series of 23 SCLC tumours on a tissue microarray. None of the 17 SCLC specimens assessable by FISH exhibited HER-2/neu gene amplification as defined by a HER-2/neu/chromosome 17 ratio = or > 2. Twelve of 17 (70.1%) SCLC samples were polysomic for chromosome 17 with corresponding increases in HER-2/neu gene copy numbers. Intermediate levels of protein expression corresponding to AQUA scores in the range of 4-24 were detected in all 23 specimens. High protein expression levels corresponding to AQUA scores up to 83, observed previously in association with gene amplification and poor prognosis in breast cancer cases, were not detected in the present study. No statistically significant association was observed between absolute chromosome 17 or HER-2/neu gene copy numbers and protein expression levels in tumour cells (P > 0.45).


CONCLUSIONS
The lack of gene amplification and robust HER-2/neu protein expression in SCLC tumour cells in this series does not suggest a prominent role for the HER-2/neu gene in SCLC tumour progression and does not support the general applicability of targeted immunotherapy with trastuzumab to this malignancy.
Giltnane
J M
JM
Section of Medical Oncology, Yale University School of Medicine, New Haven, CT 06510, USA.
Murren
J R
JR
Rimm
D L
DL
King
B L
BL
D000368:Aged; D000369:Aged, 80 and over; D001331:Automation / Q000379:methods; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods*; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D046888:Tissue Array Analysis
D018719:Erb-b2 Receptor Tyrosine Kinases