早幼粒细胞白血病蛋白在肺癌中的表达及其临床意义

Expression of promyelocytic leukaemia protein in lung carcinomas and clinical significance thereof

目的研究早幼粒细胞白血病蛋白(PML)在肺癌中的表达及其与临床预后的关系。方法利用组织芯片进行SP免疫组织化学染色,检测PML蛋白在148例肺癌、5例良性肺肿瘤和7例肺正常组织中的表达。结果4例肺癌组织没有达到评价标准而被排除。2例肺良性肿瘤和1例正常支气管黏膜细胞核明显表达PML;非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)细胞核PML表达率分别为31.4%和8.7%(χ2=4.968,P=0.026)。PML在SCLC和NSCLC细胞质的表达率分别为39.1%和14%(χ2=6.609,P=0.010)。PML阳性和阴性SCLC的术后5年累积生存率分别为50%和23%(Log-Rank:χ2=3.931,P=0.047)。COX多因素分析示PML表达是SCLC预后的独立影响因素。结论PML表达可能与SCLC患者生存期延长相关。

Objective To investigate the expression of promyelocytic leukaemia （PML） protein in lung carcinomas and the clinical significance thereof. Methods A tumor tissue microarray with lung samples from 148 patients with lung carcinoma and 5 patients with pulmonary benign tumor, and 7 patients with other benign diseases resected during operation. The cases with at least triplicate 0.6-mm cores per tumor or tissue were analyzed. Immunohistochemistry （SP method） was used to detect the expr4ession of PML protein. The association between PML expression and pest-operational survival was evaluated. Results Four cases of lung carcinoma were excluded because their available cores were less than 3. The remaining 144 lung carcinoma cases included 45 cases with squamous cell carcinoma, 62 with adenocareinoma, 23 with small cell lung carcinoma （SCLC）, 7 with large cell carcinoma, 5 with pleomorphic carcinoma, 1 with careinoid, and 1 with adenosquamous carcinoma. Forty of the 144 cases were PML protein positive in the nucleus, 26 were PML protein positive in the cytoplasm, and 12 were PML protein positive in beth the nucleus and cytoplasm. Among the 5 cases with benign lung tumors, two cases with pulmonary leiomyomas had strong expression of PML. Among the 7 normal pulmonary tissues, one case with bronchial mucosa had a moderate expression of PML on the nuclei in the basilar part, and the 6 cases with normal alveolar epithelium did not express PML. The rates of PML expression on cell nuclei were 31.4% and 8. 7% respectively in the non-small cell lung carcinoma （NSCLC） and SCLC samples （x^2 = 4. 968, P =0. 026）. Fairish, but not strong, expression on cytoplasm was found in 39. 1% cases of SCLC and in 14% cases of NSCLC （ x^2 = 6. 609, P = 0. 010）. PML protein was found in 9 patients with SCLC, but absent in the other 14 cases. The 5-year cumulative survival rate of the PML positive SCLC patients, was 50%, significantly higher than that of the PML-negative SCLC patients （23%, x^2 = 3. 931, P =0. 047）. Lack of PML protein （RR =0. 127, 95% CI= [0.027,0.592]） and senior pathologic TNM stage （RR =3. 148, 95% CI= [1. 029, 9.631] ） were two hazardous factors that influenced long-term survival of postoperative SCLC patients. Conclusion As an important suppressor of tumor, PML may be a useful indicator to predict postoperative prognosis in patients with SCLC.