层粘连蛋白-5在小尺寸肺腺癌中的表达增加及其预后意义。102例病例的免疫组织化学分析。

Increased expression of laminin-5 and its prognostic significance in lung adenocarcinomas of small size. An immunohistochemical analysis of 102 cases.

作者信息

Moriya Y, Niki T, Yamada T, Matsuno Y, Kondo H, Hirohashi S

机构信息

Diagnostic Pathology, Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, Japan.

出版信息

Cancer. 2001 Mar 15;91(6):1129-41. doi: 10.1002/1097-0142(20010315)91:6<1129::aid-cncr1109>3.0.co;2-c.

DOI:10.1002/1097-0142(20010315)91:6<1129::aid-cncr1109>3.0.co;2-c

PMID:11267958

Abstract

BACKGROUND

Laminin-5 plays an important role in cell migration during tissue remodeling and tumor invasion.

METHODS

The authors studied the expression of laminin-5 immunohistochemically in 102 cases of small-sized lung adenocarcinoma (maximum dimension < or = 2 cm) using a monoclonal antibody against the laminin gamma2 chain, and they also investigated the associations of laminin-5 with clinicopathologic characteristics. Prognostic significance of increased laminin-5 expression was evaluated using the Kaplan-Meier method and the Cox proportional hazard model.

RESULTS

Overall, laminin-5 expression was observed in 82 cases (80.4%): 7 of 18 (38.9%) bronchioloalveolar carcinomas and 75 of 84 (89.3%) invasive adenocarcinomas. Laminin-5 was preferentially localized in the cytoplasm of tumor cells at the tumor-stromal interface, where budding or dissociation of cancer cells was frequently observed. Overexpression of laminin-5 (24 cases, 23.5%) was associated with vascular invasion (P = 0.021) and stromal fibroblastic reaction (P = 0.005) but not with nodal involvement, lymphatic invasion, or pleural invasion. Survival analysis revealed that overexpression of laminin-5 was associated with shorter patient survival (P = 0.0027 by log rank test). On multivariate analysis, overexpression of laminin-5 was an independent prognostic factor (P = 0.030), as were nodal involvement (P < 0.0001), vascular invasion (P = 0.047), and lymphatic invasion (P = 0.0047) in a whole cohort of patients. Moreover, when patients with Stage I (International Union Against Cancer [UICC] staging system) disease were considered in multivariate analysis, overexpression of laminin-5 was the only significant prognostic factor (P = 0.022), whereas vascular invasion had a marginally significant impact (P = 0.07) on patient survival.

CONCLUSIONS

The authors' results showed that laminin-5 is frequently expressed by cancer cells at the invasive front of lung adenocarcinoma. The study concluded that overexpression of laminin-5 may be a useful prognostic factor in patients with small-sized lung adenocarcinoma, especially in Stage I cases.

摘要

背景

层粘连蛋白-5在组织重塑和肿瘤侵袭过程中的细胞迁移中起重要作用。

方法

作者使用抗层粘连蛋白γ2链的单克隆抗体，对102例小尺寸肺腺癌（最大直径≤2 cm）进行层粘连蛋白-5免疫组化表达研究，并调查层粘连蛋白-5与临床病理特征的相关性。使用Kaplan-Meier法和Cox比例风险模型评估层粘连蛋白-5表达增加的预后意义。

结果

总体而言，82例（80.4%）观察到层粘连蛋白-5表达：18例细支气管肺泡癌中的7例（38.9%）和84例浸润性腺癌中的75例（89.3%）。层粘连蛋白-5优先定位于肿瘤-基质界面处肿瘤细胞的细胞质中，在此处经常观察到癌细胞的出芽或解离。层粘连蛋白-5过表达（24例，23.5%）与血管侵犯（P = 0.021）和基质成纤维细胞反应（P = 0.005）相关，但与淋巴结受累、淋巴管侵犯或胸膜侵犯无关。生存分析显示，层粘连蛋白-5过表达与患者生存期缩短相关（对数秩检验P = 0.0027）。多因素分析显示，层粘连蛋白-5过表达是独立的预后因素（P = 0.030），在整个患者队列中，淋巴结受累（P < 0.0001）、血管侵犯（P = 0.047）和淋巴管侵犯（P = 0.0047）也是如此。此外，在多因素分析中考虑国际抗癌联盟（UICC）分期系统的I期疾病患者时，层粘连蛋白-5过表达是唯一显著的预后因素（P = 0.022），而血管侵犯对患者生存有边缘显著影响（P = 0.07）。