伴微乳头结构肺腺癌的临床病理特征及预后分析

Clinicalpathological Features and Outcome of Pulmonary Adenocarcinoma with a Micropapillary Pattern

目的探讨伴微乳头结构肺腺癌的临床病理特征及预后，提高对伴微乳头结构肺腺癌侵袭性及临床预后差的认识。方法回顾性分析具有完整临床病理及预后资料的浸润性肺腺癌患者299例，参照2011版肺腺癌分类标准对其组织学亚型进行判别，将其分为微乳头结构阳性组（97例）和阴性组（202例）。按微乳头结构含量多少分为微乳头（1＋）（5％～10％），微乳头（2＋）（11％～30％），微乳头（3＋）（〉30％）。结果微乳头结构为主的肺腺癌患者预后较以腺泡样为主的肺腺癌患者、乳头状为主肺腺癌患者差（P〈0．01，P〈0．01），而与实体型为主的肺腺癌患者和浸润性黏液腺癌患者相比（P均〉0．05），生存无差异。微乳头结构阳性组与阴性组相比，易于发生脉管瘤栓（P〈0．01）、胸膜侵犯（P〈0．01）及淋巴结转移（P〈0．01），并且肿瘤体积较大（P〈0．01）。微乳头结构含量多少与发生脉管瘤栓具有相天性（P〈0．01），即微乳头含量越多，发生脉管瘤栓的几率越高。微乳头阳性组与阴性组相比（PFS分别为12个月和24个月，P〈0．01），预后差。分层分析，两组在临床早期（Ⅰ＋Ⅱ期），PFS分别为18个月和37个月（P〈0．01）；中期（IIIa期），分别为8．3个月和13．6个月（P〈0．01），微乳头结构阳性组预后差：而临床晚期患者（Ⅲb＋Ⅳ期），PFS为7．7个月和11．3个月（P〉0．05），生存无差异。傲乳头结构含量多少与PFS无相关性（P〉0．05）。多因素生存分析，微乳头结构（HR，1．467；95％CI，1．089．1．975；P〈0．05）可作为独立预后因素。结论肺腺癌中的微乳头结构具有较强的侵袭性，提示预后不良。尤其是在早期伴微乳头结构肺腺癌患者，复发率高和预后差。阂此，应采取相应治疗措施，延长患者生存期。

Objective To investigate the clinicopathological feature and outcome of pulmonary adenocarcinoma with a micropapillary pattern （MPPAC） and to improve the understanding of the aggressiveness and poor prognostic influence of MPPAC. Methods 299 patients with invasive lung adenocarcinomas were analyzed retrospectively and tumor histological patterns were reassessed by two pathologists according to the Study of Lung Cancer/American Thoracic Society/European Respiratory Society （ IASLC/ATS/ERS） criteria. Patients were divided into 2 major groups： MPP-positive group and MPP-negative group. The MPP-positive group was further subdivided according to presence and proportion of MPP： MPP1 ＋（ 5% - 10% of the MPP） , MPP2 ＋ （ 10% ~ 30% of the MPP）, and MPP3 ＋ （ 〉 30% of the MPP）. Results The progression-free survival （PFS） for patients with micropapillary predominant subtype, which was significantly shorter than those with acinar predominant subtypes （ P 〈 0.01） or those with papillary predominant subtype （ P 〈 0.01） ,not with those with solid predominant subtype （ P 〉 0.05） and those with invasive mucin adenocarcinoma （ P 〉 0.05）. Compared with the MPP-negative group, the MPP-positive group was significantly correlated with vascular invasion （ P 〈 0.01） , pleural effusion （ P 〈 0.01） , lymph node metastasis （ P 〈 0.01） and tumor size （ P 〈 0.01）. The extent of MPP showed significant association with vascular invasion （ P 〈 0.01）. MPP-positive group had poorer prognosis than MPP-negative group （ 12.0 months vs 24.0 months, P 〈 0.01）. However, stratification analysis showed that MPP positive group had worse outcome comparing with MPP-positive group at stage Ⅰ ＋ Ⅱ ＋ Ⅲ A （ for stage Ⅰ ＋ Ⅱ ,18.0 months vs. 37.0 months, P 〈 0. 01; for stage Ⅲ a, 8.3 months vs 13.6 months, P 〈 0.01）. But yet, there was no significant difference between the 2 group at stageⅢ b ＋ Ⅳ （7.7 months vs. 11.3 months, P 〉 0.05）. The extent of MPP was not significantly correlated with PFS （P 〉 0.05）. By multivariate analysis, MPP （ HR, 1.467; 95% CI, 1.089-1.975; P 〈 0.05） was independent prognostic factors influencing progression-free survival.Conclusions MPP in lung adenocarcinoma is more aggressive and a poor prognostic factor. Patients with MPPAC, especially the early stage patients, have a high risk for disease recurrence and metastasis. For patients with MPPAC we should provide proper treatment to prolong the survival time.