Correlation between c-erbB-4 receptor expression and response to gemcitabine-cisplatin chemotherapy in non-small-cell lung cancer.
BACKGROUND
While the overexpression of c-erbB gene family in several malignancies is associated with poorer prognosis, the association between the expression of the cellular markers and the response to chemotherapy is not yet clear. In this study we investigated the expression of c-erbB-4 receptor in NSCLC and correlated it with the response to gemcitabine-cisplatin combination chemotherapy.


METHODS
Forty-three NSCLC patients with histologically or cytologically proven disease were treated with gemcitabine-cisplatin combination chemotherapy. Immunohistochemical stains for c-erbB-4 receptor were performed in 20 cases on paraffin sections using the avidin-biotin-peroxidase method.


RESULTS
Two patients achieved complete response (5%), and 16 achieved partial response (37%) yielding an overall objective response rate of 42%. Minimal response was observed in seven patients (16%) and disease stabilization in 7%. Immunohistochemical stain was positive for the presence of c-erbB-4 receptor in 25% of patients, and negative in 75%. No response was documented in c-erbB-4 positive patients (0 of 5) while an objective response (complete, partial or minimal) was seen in 11 of 15 (73%) c-erbB-4 negative patients. Negative stain for c-erbB-4 significantly favored response to gemcitabine-cisplatin combination (P < 0.01).


CONCLUSIONS
C-erbB-4 expression status showed no correlation with survival and cannot be accepted at this time as a guiding factor for therapeutic management. These interesting results deserve further evaluation in a large-scale prospective trial before treatment recommendations on the basis of c-erbB-4 presence can be finally made.
Merimsky
O
O
Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Israel. merimsky@zahav.net.il
Staroselsky
A
A
Inbar
M
M
Schwartz
Y
Y
Wigler
N
N
Mann
A
A
Marmor
S
S
Greif
J
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D000093542:Gemcitabine
D009363:Neoplasm Proteins; D003841:Deoxycytidine; D066246:ErbB Receptors; D002945:Cisplatin; D000093542:Gemcitabine