Relevance of p53, bcl-2 and Rb expression on resistance to cisplatin-based chemotherapy in advanced non-small cell lung cancer.
OBJECTIVE
Tumors with p53 overexpression have been associated with enhanced resistance to cisplatin-based chemotherapy in a few and small studies involving non-small cell lung cancer. The relationships and interactions between p53, Rb and bcl-2 immunostaining, clinical parameters and response to cisplatin-based chemotherapy were evaluated in the present study.


METHODS
Histological specimens obtained by bronchial or fine-needle biopsy from patients who underwent cisplatin-based chemotherapy between 1992 and 1999 were evaluated by immunostaining.


RESULTS
There were 102 patients, 88 men. Median age was 63 years; 47 had stage III and 55 stage IV disease. Forty-six tumor samples (45%) had positive immunostaining for p53, 61 (59%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for bcl-2. The response rate of the group with p53 positive immunostaining was 26% versus 57% of the p53 negative group (P=0.004). In multivariate analyses p53 positive immunostaining was identified as an independent predictive factor for resistance to cisplatin-based chemotherapy (P=0.006).


CONCLUSIONS
Our study confirmed an association of p53 immunostaining and response rate of patients treated with cisplatin-based chemotherapy.
Gregorc
Vanesa
V
Division of Medical Oncology, Policlinico Monteluce, Perugia, Italy. vgregorc@hotmail.com
Ludovini
Vienna
V
Pistola
Lorenza
L
Darwish
Samir
S
Floriani
Irene
I
Bellezza
Guido
G
Sidoni
Angelo
A
Cavaliere
Antonio
A
Scheibel
Massimo
M
De Angelis
Verena
V
Bucciarelli
Emilio
E
Tonato
Maurizio
M
D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012907:Smoking; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin