Faggiano Antongiulio, Sabourin Jean-Cristophe, Ducreux Michel, Lumbroso Jean, Duvillard Pierre, Leboulleux Sophie, Dromain Clarisse, Colao Annamaria, Schlumberger Martin, Baudin Eric
Department of Nuclear Medicine and Endocrinological Oncology, Gustave-Roussy Institute, Villejuif, France.
Cancer. 2007 Jul 15;110(2):265-74. doi: 10.1002/cncr.22791.
Poorly differentiated large cell neuroendocrine carcinomas (LCNEC) comprise a rare and still scarcely known subgroup of neuroendocrine tumors. The objective of this study was to investigate the epidemiology, clinical presentation, prognostic factors, and molecular pathways of patients with poorly differentiated LCNEC.
Forty-one patients who had a confirmed diagnosis of poorly differentiated LCNEC according to the criteria of the most recent World Health Organization classification of neuroendocrine tumors of the lung entered the study. The clinicopathologic features of patients with poorly differentiated LCNEC were reviewed, prognostic parameters for their survival were studied, and the prognostic roles of the proteins involved in cell cycle regulation were investigated with tissue array analysis in a subset of patients with LCNEC.
Twenty-four men and 17 women with a median age of 63 years (age range, 26-81 years) who had LCNEC were studied. LCNEC developed after therapy for a first cancer in 14% of patients. Neither a personal or familial history of endocrine tumors nor a primary association that was compatible with an inherited syndrome was observed. The increase of at least 1 serum biologic marker was observed in 93% of patients. A primary tumor was identified in only 63% patients. Thirty-one patients had distant metastases, and 10 patients had only lymph node metastases at the time of the diagnosis. The 5-year survival rate was 24%. High mitotic count, low expression of neuroendocrine markers, and a Bcl-2/Bax ratio > 1 were unfavorable prognostic factors for survival (P < .01). All patients who had isolated peripheral lymph node LCNEC achieved a cure.
The results from this study highlighted distinctive clinical features and prognostic indicators of poorly differentiated LCNEC. Peripheral isolated lymph node clinical presentation is proposed as a new clinical entity.
低分化大细胞神经内分泌癌（LCNEC）是神经内分泌肿瘤中一个罕见且仍知之甚少的亚组。本研究的目的是调查低分化LCNEC患者的流行病学、临床表现、预后因素和分子途径。
根据世界卫生组织最新的肺神经内分泌肿瘤分类标准确诊为低分化LCNEC的41例患者进入本研究。回顾了低分化LCNEC患者的临床病理特征，研究了其生存的预后参数，并在一部分LCNEC患者中通过组织芯片分析研究了参与细胞周期调控的蛋白质的预后作用。
研究了24例男性和17例女性LCNEC患者，中位年龄63岁（年龄范围26 - 81岁）。14%的患者在首次癌症治疗后发生LCNEC。未观察到内分泌肿瘤的个人或家族史，也未观察到与遗传综合征相符的原发性关联。93%的患者观察到至少一种血清生物标志物升高。仅63%的患者发现原发性肿瘤。31例患者有远处转移，10例患者在诊断时仅有淋巴结转移。5年生存率为24%。高有丝分裂计数、神经内分泌标志物低表达以及Bcl-2/Bax比值>1是生存的不良预后因素（P <.01）。所有孤立性外周淋巴结LCNEC患者均治愈。
本研究结果突出了低分化LCNEC独特的临床特征和预后指标。外周孤立淋巴结临床表现被提议作为一种新的临床实体。
