粒细胞集落刺激因子在非小细胞肺癌组织中的表达及其临床病理意义

Expression of granulocyte colony stimulating factor in patients with non-small cell lung cancer and its clinicopathological significance

目的观察粒细胞集落刺激因子（G—CSF）在非小细胞肺癌（NSCLC）中的表达并探讨其临床病理意义。方法收集解放军总医院2001—2010年伴有大量粒细胞浸润的NSCLC53例，同时选用无粒细胞浸润的NSCLC61例作对照，共114例。观察癌组织中粒细胞浸润情况，同时用免疫组织化学（EnVision法）检测癌组织中G—CSF的表达情况。对G—CSF表达情况及其与NSCLC临床病理特征的关系进行统计学分析，并随访全部患者，分析G—CSF表达对预后的影响。结果114例NSCLC中55例癌细胞表达G—CSF。其中大细胞癌41例（41／54，75．9％），腺癌9例（9／30，30．0％），鳞状细胞癌5例（5／30，16．7％）。G—CSF表达与癌组织中粒细胞浸润、组织学类型、坏死、肿瘤分级、局部淋巴结转移和远处转移、复发密切相关（P〈0．01），而与原发肿瘤大小无密切关联（P〉0．05）；表达阳性者发生坏死、淋巴结转移、远处转移复发的相对危险度分别是阴性者的5．57、6．28和5．24倍（P〈0．05）。阳性者与阴性者中位生存期分别为42和62个月，5年生存率分别为0和12．1％，生存期间的差异具有统计学意义（P〈0．01）。结论部分NSCLC能产生G—CSF，且以大细胞癌最常见。产生G—CSF的NSCLC组织分化差，异型性明显，恶性度高；易发生广泛坏死，常伴有粒细胞浸润；易发生淋巴结转移、远处转移和复发；生存率低，预后差。

Objective To examine granulocyte colony stimulating factor （G-CSF） expression in human non-small cell lung cancer（NSCLC） as well as discuss its clinicopathological significance. Methods Specimens were obtained from 114 cases （53 cases with granuloeyte infiltration）diagnosed pathologically as NSCLC in General Hospital of PLA. Paraffin-embedded tissues from these 114 cases of NSCLC were examined for expression of G-CSF by immunohistochemical staining. Correlation between G-CSF expression and pathological features, clinical manifestation, prognosis of patients with NSCLC was analyzed statistically. All the patients were retrospectively followed-up. Results Fifty-five of the 114 NSCLC specimens expressed G-CSF, and among these 41 （41/54,75.9%） were large cell carcinoma, nine （9/30,30. 0% ） were adenocarcinoma and five （5/30, 16.7% ） were squamous cell carcinoma. The expression was significantly correlated with infiltration of tumor mass by neutrophilic granulocytes, histological type, necrosis, differentiation, lymph node metastases, distant metastases, recurrence and survival period （P 〈 0. 01 ）. There was no significant correlation with primary tumor size （ P 〉 0. 05 ） . Logistic muhi-factor analysis revealed that necrosis, lymph nodes metastases and distant metastases RR （risk ratio） in G-CSF positive group was 5.57, 6. 28 and 5.24 times higher than those of G-CSF negative group （ P 〈 0. 05 ）. There were remarkable difference of 5-year survival rates （0 and 12. 1% respectively ） and survival period （ 42 and 62 months respectively） between positive and negative groups （ P 〈 0. 01 ）. Conclusions NSCLC with G-CSF excretion are mainly large cell lung cancer. The pathologic characteristics of these cases with G-CSF expression included poor differentiation, remarkable atypia, prominent necrosis and infiltration of tumor mass by neutrophils or emperipolesis. These tumors are usually more aggressive in biological behavior and have worse prognosis than those without G-CSF expression.