I期非小细胞肺癌患者神经内分泌分化和激素产生的预后意义

Prognostic implications of neuroendocrine differentiation and hormone production in patients with Stage I nonsmall cell lung carcinoma.

作者信息

Pelosi Giuseppe, Pasini Felice, Sonzogni Angelica, Maffini Fausto, Maisonneuve Patrick, Iannucci Antonio, Terzi Alberto, De Manzoni Giovanni, Bresaola Enrica, Viale Giuseppe

机构信息

Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy.

出版信息

Cancer. 2003 May 15;97(10):2487-97. doi: 10.1002/cncr.11376.

DOI:10.1002/cncr.11376

PMID:12733148

Abstract

BACKGROUND

Approximately 10-20% of nonsmall cell lung carcinomas (NSCLC) show neuroendocrine (NE) differentiation, as evaluated by panendocrine markers or ultrastructural evidence of dense-core secretory granules. However, little is known regarding the prevalence and clinical implications of NE differentiation in patients with Stage I NSCLC.

METHODS

The authors analyzed 220 consecutive patients with Stage I NSCLC (pT1-T2N0M0) among 2100 patients with primary lung carcinoma who underwent surgical treatment between 1987 and 1993. Using light microscopy and immunohistochemical staining for synaptophysin, chromogranin A, and respiratory tract-related hormones, 28 NSCLC specimens with NE differentiation (NSCLC-ND) and 11 large cell neuroendocrine carcinoma (LCNEC) specimens were identified.

RESULTS

The 28 NSCLC-ND specimens included 15 adenocarcinomas and 13 squamous cell carcinomas. Neoplastic cells with NE features never exceeded 20% in NSCLC-ND specimens, whereas neoplastic cells amounted to 20-90% in LCNEC specimens. NSCLC-ND specimens with > 5% NE-differentiated tumor cells showed increased Ki-67 labeling index (P = 0.007) and invasive phenotype, as evaluated by fascin immunoreactivity (P = 0.021). Patients with adenocarcinoma, but not with squamous cell carcinoma, who had > 5% NE-differentiated cells had a worse clinical course compared with patients who had ordinary NSCLC, with reduced overall survival (P = 0.017) and disease free survival (P = 0.049). In multivariate analysis, NE differentiation > 5% neoplastic cells in patients with adenocarcinoma independently predicted a poorer prognosis (hazard ratio, 2.61; 95% confidence interval, 0.99-6.85). Hormone production was restricted to chromogranin positive NSCLC-ND but did not affect prognosis.

CONCLUSIONS

Stage I adenocarcinomas with >or= 5% NE tumor cells are clinically aggressive tumors, similar to LCNEC. Hormone production identifies a more fully developed neuroendocrine phenotype but is not relevant to prognosis. The identification of NE-differentiated cells in patients with NSCLC may have clinical relevance.

摘要

背景

通过全内分泌标志物或致密核心分泌颗粒的超微结构证据评估，约10%-20%的非小细胞肺癌（NSCLC）表现出神经内分泌（NE）分化。然而，关于I期NSCLC患者中NE分化的发生率及临床意义知之甚少。

方法

作者分析了1987年至1993年间接受手术治疗的2100例原发性肺癌患者中的220例连续I期NSCLC患者（pT1-T2N0M0）。使用光镜及针对突触素、嗜铬粒蛋白A和呼吸道相关激素的免疫组化染色，鉴定出28例具有NE分化的NSCLC标本（NSCLC-ND）和11例大细胞神经内分泌癌（LCNEC）标本。

结果

28例NSCLC-ND标本包括15例腺癌和13例鳞状细胞癌。具有NE特征的肿瘤细胞在NSCLC-ND标本中从未超过20%，而在LCNEC标本中肿瘤细胞占20%-90%。NE分化肿瘤细胞>5%的NSCLC-ND标本显示Ki-67标记指数增加（P = 0.007），且通过丝状肌动蛋白免疫反应性评估具有侵袭性表型（P = 0.021）。腺癌患者而非鳞状细胞癌患者中，NE分化细胞>5%者与普通NSCLC患者相比临床病程更差，总生存期降低（P = 0.017），无病生存期降低（P = 0.049）。在多变量分析中，腺癌患者中肿瘤细胞NE分化>5%独立预测预后较差（风险比，2.61；95%置信区间，0.99-6.85）。激素产生仅限于嗜铬粒蛋白阳性的NSCLC-ND，但不影响预后。