伴微乳头结构肺腺癌的临床病理和免疫表型特点分析

Pulmonary adenocarcinoma with micropapillary pattern ： a study

目的探讨伴微乳头结构的肺腺癌的临床病理学特征及免疫表型特点。方法收集从北京协和医院2002年1月-2008年12月间135例手术切除肺腺癌中检出的48例伴有微乳头结构肺腺癌（微乳头的成分≥10％）临床资料。分析其临床病理特点，并用免疫组织化学EnVision法染色观察黏蛋白1（Muc-1）、上皮性钙黏蛋白（E—cadherin）、β-连接蛋白（B—catenin）、表皮生长因子受体（EGFR）、p53、Ki-67的表达。结果48例伴微乳头结构的肺腺癌病例中，男性27例，女性21例，年龄43～85岁，平均年龄60．7岁。TNM分期Ⅰ期13例，Ⅱ期8例，Ⅲ期14例，Ⅳ期13例。48例中，36例均可见无血管轴心的微乳头漂浮在肺泡腔（IA型）或纤维间隙中（IB型），余12例腺癌结构类似细支气管肺泡癌样，但有微乳头向腔内突起，并有微乳头漂浮在衬覆肿瘤细胞的腔内（Ⅱ型）。35例切除标本病理检查淋巴结转移率（72．9％），30例伴淋巴管瘤栓（62．5％），与不含微乳头成分的肺腺癌比较，二者差异有统计学意义（P〈0．01）。黏附分子E—cadherin和B．catenin、Muc-1、EGFR、p53及Ki-67的阳性率分别为97．9％（47／48）、89．5％（43／48）、91．7％（44／48）、70．8％（34／48）、35．4％（17／48）、93．8％（45／48）；染色强度3＋以上高表达病例分别占阳性表达的72．3％（34／47）、90．7％（39／43）、88．6％（39／44）、52．8％（19／36）、58．8％（10／17）、46．7％（21／45）。36例患者获得随访信息，平均随访时间21．1个月，其中44．4％（16／36）患者术后生存至今，未见肿瘤发生，33．3％（12／36）患者死于肿瘤，22．2％（8／36）患者带瘤生存。结论肺腺癌中微乳头结构与淋巴结转移及淋巴管瘤栓密切相关，提示其具有高度恶性的潜能及预后不良。

Objective To study the clinicopathologic characteristics and immunohistochemical profile of lung adenoeareinomas with a micropapillary pattern （MPP）. Methods Among 135 cases of lung adenocarcinomas, the clinical, histological and immunohistochemical features of 48 cases of lung adenocarcinomas with a micropapillary components （ the micropapillary components ≥ 10% ） were studied. The literature was reviewed. Results All the 135 cases were resected pulmonary adenocarcinomas. Among 48 cases of lung adenoearcinomas with a micropapillary components, the age of patients ranged from 43 to 85 years （ mean = 60. 7 years ）. The male-to-female ratio was 9 ： 7. Histologically, 36 cases of lung adenocareinomas with the MPP were characterized by small papillary tufts lacking a central fibrovascular core lying freely within alveolar spaces （ I A type） or in the clefts of fibrous tissue just like those in MPP breast cancers （ I B type）. Another type of the micropapillary pattern consisted of 12 cases, the micropapillary tufts floating within cystic spaces lined by tumor cells （ ]1 type ）. In micropapillary pattern-positive cases, lymphatic invasion and lymph node metastasis were identified significantly more frequently than in micropapillary pattern-negative cases （ P 〈 0. 01 ）. The percentages of cases positive for various markers were 97. 9 % （ 47/48 ） forE-cadherin, 89. 5 % （ 43/48 ） for β - catenin, 91. 7 % （ 44/48 ） for Muc -1 , 70. 8% （34/48） for epidermal growth factor receptor, 35. 4% （17/48） for p53, 93.8% （45/48） for Ki-67. The percentages of eases with high expression （ including 3 ＋ or 4 ＋ ） for these markers were 72. 3% （34/47） for E-cadherin, 90. 7% （39/43） for [3-eatenin, 88.6% （39/44） for Muc-1, 52. 8% （19/36） for epidermal growth factor receptor, 58.8% （10/17） for p53, 46. 7% （16/36） for Ki-67. Adequate clinical follow-up information was available for 36 patients. The mean follow-up time was 21.1 months. Among these, 16 of 36 patients （44.4%） were alive with no evidence of tumor, 12 （33.3%） were died, and 8 （22. 2% ） were alive with tumor. Conclusion Lung adenocareinomas with the MPP correlates positively with lymphatic invasion and lymph node metastasis, and are likely to have a potential for high malignancy, suggestting a poor prognosis.