乳腺浸润性微乳头状癌临床病理分析及免疫组化研究

Clinical and pathologic features of invasive micropapillary carcinoma of the breast: an immunohistochemical study of 30 cases

目的 探讨乳腺浸润性微乳头状癌（IMC）的临床病理特点及其免疫表型在诊断、预后等方面的意义。方法 从900余例乳腺癌中筛选出符合IMC形态学和免疫标记标准的病例30例，应用免疫组化方法对该组病例进行激素受体、细胞增殖、热休克蛋白以及p53表达的研究。结果 该组病例发病年龄24～71岁，平均53岁，发生率占同期乳腺癌的3．3％，占同期乳腺浸润性导管癌的4．6％，伴腋窝淋巴结转移者15例（68．2％）。形态上，瘤细胞呈乳头状排列，由纤细的纤维血管或纤维胶原间质分隔，两者间有一透明、扩张的腔隙，呈弥漫或结节样浸润生长；IMC微乳头边缘EMA强（＋），C031（-），微乳头缺乏纤维血管轴心，E-cadherin主要表达于肿瘤细胞间连接面的细胞膜，而微乳头朝向间质面的细胞膜则表达减弱或消失。该肿瘤ER、PR、Her-2阳性率分别为53．3％、60％、13.3％；HSP70、grp94、p53阳性率分别为100％、90％、63．3％；Ki-67标记显示肿瘤细胞生长指数为5％～75％，平均27．3％。结论 IMC是一种具有特殊形态学表现的高增殖、高转移潜能的乳腺癌，结合EMA、E-cad、CD31等标记物有助于IMC的诊断和鉴别诊断。热休克蛋白与p53在1MC中的高表达提示，其在IMC的发生、发展过程中起着重要作用。

Objective Invasive micropapillary carcinoma （IMC） of the breast is a rare subtype of breast carcinoma that has an extremely high incidence of lymph node metastases and poor clinical outcome. This histological subtype of breast carcinoma has remained unclear due to the rarity of cases. The aim of this study was to analyze the clinical and pathological features of IMC and to investigate the significance of its immunophenotype. Methods We reviewed all 900 cases of primary breast carcinoma that were surgically resected at our hospital between 2001 and 2005. Of these, 30 cases of pure or partial IMC were reported and studied by light microscopy and immunohistochemistry. Results The patients were ranged in age from 24 to 71 years （mean 53 years） and 15 cases （68.2%） with axillary lymph nodes metastasis. The incidence of IMC was 3.3% of all breast cancers and 4.6% of all invasive ductal carcinoma respectively in our study. Microscopically, the tumors showed distinctive histological features： infiltrating avascular papillary or morula-like epithelial cell groups with a clear space surrounding these cells. By immunohistochemistry, EMA-positive staining was observed in the outer margin of neoplastic nests and the plasma membranes were positive for E-cadherin, but without CD31-positive endothelial cells in neoplastic nests. The neoplasm cells also showed positivity for estrogen receptor （53.3%）, progesterone receptor （60%）, Her-2 （ 13.3% ）, HSP70 （ 100% ）, grp94 （90%）, and p53 （63.3%）. Ki67 staining showed the proliferative activity of the neoplasm ranged from 5% to 75% （mean 23.3%）. Conclusions IMC has distinctive histologic features that are associated with an extremely high incidence of axillary lymph node metastases and a poor clinical outcome. EMA, E-cadherin and CD31 staining may help the diagosis and differential diagnosis. The high expression of heat shock protein and p53 indicates that they may play an important role in carcinogensis of IMC.