Expression of class III beta-tubulin correlates with unfavorable survival outcome in patients with resected non-small cell lung cancer.
BACKGROUND
We analyzed the significance of class III beta-tubulin (TUBB3) expression in curatively resected non-small cell lung cancer as a prognostic marker along with previously reported excision repair cross complementation group 1 (ERCC1).


METHODS
One hundred and thirty-six consecutive patients were included in this retrospective study. Patients who received adjuvant chemotherapy were excluded. We used immunohistochemistry to evaluate TUBB3 and ERCC1 expression on tissue microarray in duplicate. Semiquantitative H score was used for the scoring of tumor staining.


RESULTS
Sixty percent of patients had stage I disease, 17% stage II, 18% stage IIIA, and 5% stage IIIB. TUBB3 H score showed bimodal distribution with the minimum at the value of 4, which was used as a cutoff value for determination of TUBB3 positivity. TUBB3 was expressed in 60 patients (44%). Patients with a positive TUBB3 expression survived shorter than did the patients with a negative expression (5-year overall survival [OS] rate was 40% versus 61%; p = 0.005/5-year disease-free survival rate was 34% versus 55%; p = 0.024). ERCC1 expression showed tendency for prolonged OS without reaching statistical significance. A multivariate analysis that incorporated covariates including TUBB3 expression, age, stage, EGFR mutation status, histology, and ERCC1 expression showed that TUBB3 was an independent unfavorable prognostic factor for OS (hazard ratio 2.083; p = 0.008) and relapse free survival (hazard ratio 1.978; p = 0.020).


CONCLUSIONS
TUBB3 expression is an independent unfavorable prognostic marker in patients with curatively resected non-small cell lung cancer who did not receive adjuvant chemotherapy.
Koh
Youngil
Y
Departments of Internal Medicine and daggerPathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Jang
Bogun
B
Han
Sae-Won
SW
Kim
Tae-Min
TM
Oh
Do-Youn
DY
Lee
Se-Hoon
SH
Kang
Chang Hyun
CH
Kim
Dong-Wan
DW
Im
Seock-Ah
SA
Chung
Doo Hyun
DH
Kim
Young Tae
YT
Kim
Tae-You
TY
Kim
Young-Whan
YW
Kim
Joo Hyun
JH
Heo
Dae Seog
DS
Bang
Yung-Jue
YJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D046888:Tissue Array Analysis; D014404:Tubulin / Q000378:metabolism*
D004268:DNA-Binding Proteins; C498585:TUBB3 protein, human; D014404:Tubulin; C071447:ERCC1 protein, human; D004720:Endonucleases