[Expression of alpha-tubulin and MDR1 and their correlation with the biological features of non-small cell lung carcinoma].
OBJECTIVE
To detect the expression of alpha-tubulin and MDR1 in human non-small cell lung carcinoma (NSCLC), and to clarify their clinical significance.


METHODS
Paraffin embedded tissues from 158 primary non-small lung carcinomas and 30 paracancerous lung tissues were examined for expression of alpha-tubulin and MDR1 by immunohistochemistry (SP method). 30 freshly taken NSCLC tissues were examined by Western blot analysis. The relationship between alpha-tubulin and MDR1 expression and the biological features of lung carcinoma was analyzed.


RESULTS
The positive rate of alpha-tubulin and MDR1 expressions in the lung carcinomas was 65.2% and 51.3%, respectively. There was no expression of either of them in 30 paracancerous lung tissues. Western blot analysis showed that the level of alpha-tubulin and MDR1 expressions in NSCLC tissues were 0.49 +/- 0.06 and 0.56 +/- 0.04, respectively, significantly higher than that in paracancerous tissues (0.07 +/- 0.01) (t = 3.693 and t = 6.769, P < 0.01). The positive rate of alpha-tubulin expression was gradually increased with tumor progression, significantly higher in III-IV stage cancers and in poorly differentiated carcinomas (both P < 0.01). There was a distinct statistically significant difference between stage I, stage II and III, and stage IV. The positive rate of alpha-tubulin in well-moderately differentiated carcinomas was lower than that in poorly differentiated ones. There was no significant correlation with age, sex, tumor size, histological type, clinical TNM system and lymph node metastasis. The positive rate of MDR1 was not correlated with sex, age, tumor size, pathological grading, clinical TNM stages and lymph node metastasis. But the positive rate of MDR1 in adenocarcinoma was significantly higher than that in squamous carcinoma and undifferentiated large cell carcinomas (P < 0.01). alpha-tubulin and MDR1 expression had no impact on the outcome of chemotherapy (chi(2) = 0.69 and 1.30, P > 0.05, respectively). Univariate analysis showed that the 5-year survival rate of patients with negative alpha-tubulin and MDR1 expression was 30.7% and 28.5%, respectively, significantly higher than that of patients with positive alpha-tubulin and MDR1 expression (13.5% and 11.8%, respectively) (chi(2) = 20.69 and 15.52, P < 0.01, respectively), and multivariate Cox regression analysis showed that alpha-tubulin (RR = 3.287, P = 0.006) and clinical TNM stage (RR = 1.954, P = 0.025) were significantly independent predictive factor for patients with lung cancer, MDR1 and other factors could not be used as an independent predicitive factors. However, there was no significant correlation between the expression of alpha-tubulin and MDR1 in lung carcinoma(r = 0.093, P > 0.05).


CONCLUSIONS
The expression of alpha-tubulin and MDR1 may play an important role in the development and progression of human non-small cell lung carcinoma. Combined detection could be considered as an important index for predicting prognosis of lung carcinoma.
Department of Respiratory Diseases, The 117th Hospital of PLA, Hangzhou 310013, China.
Qing-yong
QY
Chen
Zhong-yong
ZY
Jiang
Li-jun
LJ
Wu
Bao-yan
BY
Zhang
Guo-hua
GH
Lu
Jian-ying
JY
Zhou
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D016016:Proportional Hazards Models; D015996:Survival Rate; D014404:Tubulin / Q000378:metabolism*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C533522:TUBA1A protein, human; D014404:Tubulin