The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection.
OBJECTIVE
The DNA repair pathway and isotype composition of beta-tubulin are known to be associated with resistance to platinum- and taxane-based chemotherapy, respectively. The aim of this study was to identify the clinical significance of excision repair cross-complementation 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), X-ray repair cross-complementation 1 (XRCC1) and betaIII-tubulin on the chemotherapy response and overall survival in patients with non-small cell lung cancer (NSCLC) who received neoadjuvant chemotherapy.


METHODS
Protein expression profiles were evaluated by immunohistochemistry on surgical specimens of 82 NSCLC patients who underwent platinum- and taxane-based neoadjuvant chemotherapy. The expression levels of proteins were measured semi-quantitatively and the correlation with tumor responses, pathologic cell death rate and survival were evaluated.


RESULTS
There were 73 (89.0%) clinical stage III patients. Lobectomy, bilobectomy, and pneumonectomy were performed in 54 (65.0%), 11 (13.4%), and 17 (20.7%) patients, respectively. There was no correlation between clinical response and protein expression. The expression levels of ERCC1, BRCA1, and XRCC1 increased proportionally to the cell death rate (p<0.05); however, betaIII-tubulin expression did not correlate with cell viability. Multivariate analysis demonstrated that early pathologic stage, adjuvant chemotherapy, high ERCC1 and low betaIII-tubulin expression were good prognostic factors for overall survival (p<0.05).


CONCLUSIONS
The inverse correlation between DNA repair proteins and cell viability suggests that these protein expression levels can be markers for chemotherapy responsiveness. However, only ERCC1 and betaIII-tubulin were prognostic factors after platinum- and taxane-based neoadjuvant chemotherapy following surgical resection.
Kang
Chang Hyun
CH
Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-744, South Korea. chkang@snu.ac.kr
Jang
Bo Gun
BG
Kim
Dong-Wan
DW
Chung
Doo Hyun
DH
Kim
Young Tae
YT
Jheon
Sanghoon
S
Sung
Sook-Whan
SW
Kim
Joo Hyun
JH
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D004268:DNA-Binding Proteins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017671:Platinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D014404:Tubulin / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1
D019313:BRCA1 Protein; D001952:Bridged-Ring Compounds; D004268:DNA-Binding Proteins; D017671:Platinum Compounds; C498585:TUBB3 protein, human; D043823:Taxoids; D014404:Tubulin; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C080625:taxane; C071447:ERCC1 protein, human; D004720:Endonucleases