乳腺具有微乳头状结构黏液癌的免疫表型及预后研究

Immunophenotyping and prognosis of mucinous micropapillary carcinomas of the breast

目的:探讨乳腺具有微乳头状结构黏液癌(mucinous micropapillary carcinomas,MUMPC)的免疫表型及预后。方法:回顾性分析天津医科大学肿瘤医院乳腺病理研究室2003年1月至2012年12月531例确诊为乳腺单纯型黏液癌(pure mucinous carcinoma,p MC)的病例,筛选出其中的MUMPC及非微乳头状结构的p MC病例(对照组p MC)。以134例MUMPC为研究组,397例对照组p MC及281例同期诊断为浸润性微乳头状癌(invasive micropapillary carcinoma,IMPC)为对照组,3组行临床病理学特征和生存与预后关系的分析比较,从以上病例中随机选取32例MUMPC、89例对照组p MC、44例IMPC,行分泌型黏蛋白(MUC2、MUC5AC、MUC6)及神经内分泌指标Syn的免疫组织化学染色,比较分析3组的免疫表型特征。结果:MUMPC的HER-2阳性率为12.5%(4/32),低于IMPC的27.3%(12/44),但高于对照组p MC的4.5%(4/89),3者之间有显著性差异(P=0.001);MUC2、MUC5AC和MUC6表达在MUMPC与对照组p MC中无显著性差异(P>0.05),仅MUC2表达在MUMPC与IMPC比较中有显著性差异(P<0.001);神经内分泌相关指标Syn表达在MUMPC与对照组p MC比较中有显著性差异(P=0.003),而MUMPC与IMPC相比无显著性差异(P>0.05)。Kaplan-Meier生存分析显示,MUMPC的无病生存期(DFS)与总生存期(OS)低于对照组p MC(P<0.001与P=0.004),但要高于IMPC。结论:MUMPC的免疫表型、临床生物学行为及预后与单纯型黏液癌和IMPC既有区别又有联系,临床诊疗中应对该类型给予足够的认识和正确归类,以避免治疗不足或过度。

Objective： To investigate immunophenotyping and prognosis of mucinous micropapillary carcinomas （MUMPC） of breast. Methods： Retrospective evaluation was performed on 531 cases with final diagnosis of pure mucinous carcinoma （pMC） of the breast in Tianjin Medical University Cancer Institute and Hospital from January 2003 to December 2012, cases with MUMPC and con- ventional pMC without micropapillary patterns were selected. A total of 134 patients with MUMPC were selected as research group, 397 cases of conventional pMC and homochronous 281 cases of invasive micropapillary carcinomas （IMPC） were selected as control groups. Clinicopathologic characteristics, survival analysis and prognosis were compared among three groups. The expression of secret- ed mucins （MUC2, MUC5AC, and MUC6） and neuroendocrine indicators synaptophysin （Syn） were detected through immunohisto- chemistry in 32 MUMPC cases, 89 conventional pMC cases and 44 IMPC cases which randomly selected from the above cases, to iden- tify discriminating immunophenotyping among the three groups. Results： The positive rate of HER-2 in MUMPC was lower than that in IMPC, but higher than that in conventional pMC （P=0.001）. Similar MUC phenotypes of MUC2, MUC5AC, and MUC6 were ob- served between MUMPC and conventional pMC. Different phenotypes of MUC2 were observed between MUMPC and IMPC （P〈 0.001）, no difference was found in MUC5AC and MUC6. In terms of neuroendocrine differentiation, similar synaptophysin phenotypes were detected in MUMPC and IMPC. The positive rate of synaptophysin was higher in MUMPC than in conventional pMC （P=-0.003）.Kaplan-Meier analysis results indicated that patients with MUMPC had poorer disease-free survival （DFS） and overall survival （OS） than those with conventional pMC; by contrast, patients with MUMPC had higher survival than patients with IMPC （log-rank for DFS= 0.000; log-rank for OS=0.004）. Conclusion： The patterns of immunophenotyping, clinical biological behavior and prognosis indicated that MUMPC exhibit dual phenotypes; these phenotypes displayed similarities and differences compared with conventional pMC and IMPC. Therefore, further studies on therapies for MUMPC should be conducted to avoid insufficient or excessive treatment, and to cor- rectly classify this type of tumor in clinical practice.