乳腺浸润性微乳头状癌Twist表达临床意义研究

目的：探讨乳腺浸润性微乳头状癌（invasivemicropapillarycarcinoma，IMPC）组织中Twist蛋白表达及其与临床病理学特征的关系和意义。方法：选取天津医科大学肿瘤医院乳腺病理研究室2008-01-01-2009-12-31收检的术前未经放化疗的103例IMPC患者石蜡包埋组织标本，并以同期108例乳腺非特殊型浸润性导管癌（invasiveductalcarci-nomanototherwisespecified，IDc-NOS）石蜡标本作为对照，采用免疫组织化学SP法检测肿瘤组织中Twist蛋白的表达水平，分析其与各临床病理学特征的关系。结果：IMPC组织Twist阳性表达率为56．3％（58／103），明显高于IDC_NOS组织的41．7％（45／108），差异有统计学意义，χ2=4．525，P=0．033。Twist的核表达与雌激素受体（endoplasmicreticulum，ER）（r=-0．301，P=0．002）呈负相关，与淋巴结转移（r=0．324，P=0．001）和软组织侵犯（r=0．428，P〈0．001）及淋巴管癌栓（r=0．507，P〈O．001）呈正相关；T胞质表达仅与ER（r=-0．262，P=0．007）呈负相关；而胞核或胞质的表达均与患者年龄、肿瘤大小、病理学分期、孕激素受体（progesteronereceptor，PR）和HER-2的表达无明显相关性，P〉0．05。Kaplan-Meier生存分析显示，Twist阳性表达的IMPC患者无病生存（DFS）低于Twist阴性表达患者，P=0．002；多因素分析显示，Twist表达及淋巴结转移是IMPC患者DFS的独立预后因子，相对危险度分别为2．771、2．202，P值分别为0．046，0．014。结论：Twist在乳腺IMPC组织中过表达，提示其可能在IMPC高侵袭、高转移中发挥重要作用，有可能成为靶向治疗研究的新靶点。

Expressions and clinical significance of Twist protein in invasive micropapillary carcinoma of the breast tissues

OBJECTIVE：To investigate the expression of Twist in invasive micropapillary carcinoma （IMPC） of the breast and the relationship between them, and their significance in relation to cancer clinicopathological characteristics. METHODS： The expressions of Twist protein was determined by immunohistochemical SP staining in 103 cases of IMPC and 108 cases of invasive ductal carcinoma not otherwise specified （IDC-NOS） from Tianjin Medical University Cancer In- stitute and Hospital 2008-01-01- 2009-12-31, undergoing without preoperative chemotherapy and radiotherapy. RE- SULTS： Twist expressions in IMPC and IDC-NOS tissues were 56.3% （58/103） and 41.7 （45/108）, differences were sta- tistically significant （χ2=4. 525,P=0. 033）. Nuclear expression of Twist was negatively correlated with the estrogen re- ceptor （r= --0. 301 ,P=0. 002） and was positively correlated with metastasis in lymph nodes （r= 0. 324,P= 0. 001）, lymphovascular invasion （r= 0. 507, P〈0. 001） and extranodal extension （r= 0. 428, P〈0. 001）; cytoplasm expression of Twist was only negatively correlated with the estrogen receptor （r=- 0. 262, P= 0. 007）. No correlation was found between Twist and the patient＇s age, tumor size, pathologic stage and progesterone receptor or human epidermal growth factor receptor 2. Kaplan-Meier analysis indicated that IMPC patients with Twist positive expression showed a lower dis- ease-free survival （DFS） compared to the patients with Twist negative expression （log-rank test,P= 0. 002）. Multivariate analysis showed that high expression of Twist and lymph nodes status were independent risk factors that could predict the survival of IMPC patients （RR= 2. 771 and 2. 202,P = 0. 046 and 0. 014, respectively）. CONCLUSIONS： Twist shows over-expression in IMPC and may play an important role in aggressiveness and higher metastatic risk of IMPC of the breast. It can be a new method to develop drugs targeting twist in IMPC of breast.