Lazzaro B, Anderson A E, Kajdacsy-Balla A, Hessner M J
Department of Surgical Pathology, Medical College of Wisconsin, Milwaukee, USA.
Appl Immunohistochem Mol Morphol. 2001 Sep;9(3):234-41. doi: 10.1097/00129039-200109000-00007.
Medullary carcinoma of the breast has attracted attention because of its relatively good prognosis, in spite of its high cytologic grade. It has, by definition, a consistent, florid tumor infiltrating lymphocyte (TIL) population, probably the result of cytotoxic T-lymphocytes recognizing tumor cells in an HLA-DR-restricted manner. HLA-DR tends to be more highly expressed on primary medullary carcinoma cells than on ductal carcinoma cells; however, the MHC-class II antigenicity of the tumor cells themselves has not been analyzed extensively, and as yet there has been no comparative study of HLA-DR expression in medullary and ductal carcinomas metastatic to lymph nodes. Eleven cases of medullary carcinoma and 15 cases of ductal carcinoma, primaries, and respective lymph node metastases were analyzed by immunoperoxidase staining for HLA-DR and lymphocytes antigens. Polymerase chain reaction (PCR) analysis to identify HLA-DR subtypes from the paraffin blocks was performed on selected cases of primaries and nodal metastases of both tumor types. Immunoperoxidase staining for HLA-DR antigen revealed a marked difference in antigen expression between medullary and ductal carcinomas. In the medullary carcinomas, the mean percentage of cells staining for HLA-DR was 74.5% in the primary tumors and 67.3% in the nodal metastases. For the ductal carcinomas, the mean percentage of cells staining was 17.7% in the primaries and 7% in the metastases. There was a tendency for the level of HLA-DR expression to remain high in medullary carcinoma metastatic to nodes, whereas whatever HLA-DR was present within ductal primaries tended to diminish when cells metastasized to regional nodes. PCR analysis of the HLA-DR within the two tumor types revealed no emerging subtype or variant that could be associated with either the medullary or the ductal carcinomas. Medullary carcinoma cells express much greater quantities of HLA-DR, on the whole, than ductal carcinomas. Expression of HLA-DR is retained on medullary carcinoma cells that have spread to lymph nodes, whereas the smaller quantities of HLA-DR present within ductal primaries tend to diminish even further when the tumor cells are found in lymph nodes. No discernible HLA-DR mutations or predominant subtypes emerged on PCR analysis, and the authors therefore conclude that it is the quantity and not the quality of HLA-DR expression in medullary carcinoma that maintains the characteristic TIL infiltrate, not seen in ductal carcinomas.
乳腺髓样癌尽管细胞学分级高，但因其预后相对较好而受到关注。根据定义，它有一致的、丰富的肿瘤浸润淋巴细胞（TIL）群体，这可能是细胞毒性T淋巴细胞以HLA - DR限制方式识别肿瘤细胞的结果。HLA - DR在原发性髓样癌细胞上的表达往往比导管癌细胞上更高；然而，肿瘤细胞本身的MHC - II类抗原性尚未得到广泛分析，并且目前还没有对转移至淋巴结的髓样癌和导管癌中HLA - DR表达进行比较研究。通过免疫过氧化物酶染色检测HLA - DR和淋巴细胞抗原，分析了11例髓样癌和15例导管癌的原发性肿瘤及其各自的淋巴结转移灶。对两种肿瘤类型的原发性肿瘤和淋巴结转移灶的选定病例进行聚合酶链反应（PCR）分析，以从石蜡块中鉴定HLA - DR亚型。HLA - DR抗原的免疫过氧化物酶染色显示髓样癌和导管癌之间抗原表达存在显著差异。在髓样癌中，原发性肿瘤中HLA - DR染色阳性细胞的平均百分比为74.5%，淋巴结转移灶中为67.3%。对于导管癌，原发性肿瘤中染色阳性细胞的平均百分比为17.7%，转移灶中为7%。转移至淋巴结的髓样癌中HLA - DR表达水平有保持较高的趋势，而导管原发性肿瘤中无论存在何种HLA - DR，当细胞转移至区域淋巴结时往往会减少。对两种肿瘤类型中的HLA - DR进行PCR分析，未发现与髓样癌或导管癌相关的新出现的亚型或变体。总体而言，髓样癌细胞表达的HLA - DR量比导管癌细胞多得多。HLA - DR的表达在已扩散至淋巴结的髓样癌细胞上得以保留，而导管原发性肿瘤中存在的少量HLA - DR在肿瘤细胞出现在淋巴结中时往往会进一步减少。PCR分析未出现可识别的HLA - DR突变或主要亚型，因此作者得出结论，髓样癌中维持特征性TIL浸润的是HLA - DR表达的量而非质，而导管癌中则未见这种浸润。
