Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast
Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast
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乳腺癌浸润性微乳头状癌和髓样癌中肿瘤浸润淋巴细胞的差异
DOI：
10.1038/modpathol.2008.72
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发表时间：
2008-09-01
期刊：
影响因子：
7.5
通讯作者：
Fu, Li
中科院分区：
文献类型：
--
作者：
Guo, Xiaojing;Fan, Yu;Fu, Li
肿瘤浸润性淋巴细胞与某些肿瘤预后较好相关，乳腺髓样癌就是一个很好的例子。然而，在最近对乳腺浸润性微乳头状癌的研究中，肿瘤浸润性淋巴细胞与淋巴结转移增加和预后不良相关。为了探讨这种免疫反应和肿瘤行为差异的可能机制，对28例淋巴细胞明显浸润的浸润性微乳头状癌和29例髓样癌进行了比较。在两种肿瘤中，肿瘤浸润性淋巴细胞以T淋巴细胞为主(P<；0.01)，以CD8+T细胞为主(P<；0.01)。CD8+细胞毒性T淋巴细胞在两种类型肿瘤中的功能存在显著差异。髓样癌的间质和上皮组织均有淋巴细胞浸润，而浸润性微乳头状癌的肿瘤浸润性淋巴细胞几乎仅限于间质。髓样癌肿瘤浸润性淋巴细胞FasL表达强于浸润性微乳头状癌(P<；0.01)，髓样癌细胞Fas表达强于浸润性微乳头状癌(P<；0.01)。免疫组织化学双重染色显示，在(++/++)Fas强表达的肿瘤亚组中，髓样癌的肿瘤浸润性淋巴细胞，尤其是浸润性微乳头状癌的肿瘤浸润性淋巴细胞，以CD8+细胞毒性T淋巴细胞为主，而浸润性微乳头状癌则不是。此外，髓样癌组织中细胞毒性T淋巴细胞表达穿孔素、颗粒酶B和FasL的水平明显高于浸润性微乳头状癌(P<；0.01)。提示肿瘤浸润性淋巴细胞在不同肿瘤中提供的有效免疫功能不同，浸润性微乳头状癌相对缺乏杀伤肿瘤的细胞毒性T细胞可能部分解释了肿瘤浸润性淋巴细胞与乳腺浸润性微乳头状癌生物学行为的不良相关性。
Tumor infiltrating lymphocytes have been correlated with a better prognosis for some tumors and medullary carcinoma of breast is a good example. However, in a recent study of invasive micropapillary carcinoma of breast, tumor infiltrating lymphocytes were associated with increased lymph node metastasis and a poorer prognosis. To explore possible mechanisms underlying this difference in immune responsiveness and tumor behavior, 28 cases of invasive micropapillary carcinoma with prominent lymphocyte infiltration were compared with 29 cases of medullary carcinoma. In both tumors, the majority of tumor infiltrating lymphocytes were T lymphocytes (P < 0.01) with CD8+ T lymphocytes predominant (P < 0.01). Significantly, functional differences in CD8+ cytotoxic T lymphocytes were identified in the two types of tumor. While lymphocytes infiltrated both the stroma and epithelial components of medullary carcinoma, the tumor infiltrating lymphocytes of invasive micropapillary carcinoma were almost exclusively confined to the stroma. Tumor infiltrating lymphocytes of medullary carcinoma showed stronger expression of FasL than those in invasive micropapillary carcinoma (P < 0.01) and medullary carcinoma cells exhibited stronger expression of Fas than invasive micropapillary carcinoma cells did (P < 0.01). In the subgroups of tumors with strong (+ +/ + +) Fas expression, double immunohistochemistry revealed that most of the tumor infiltrating lymphocytes in medullary carcinoma, particularly those infiltrating the tumor nests, were CD8+ cytotoxic T lymphocytes, but not so in invasive micropapillary carcinoma. Furthermore, upregulated expression of perforin, granzyme B and FasL by cytotoxic T lymphocytes was greater in medullary carcinoma than invasive micropapillary carcinoma (P < 0.01, respectively). The results suggest that effective immunity provided by tumor infiltrating lymphocytes varies in different tumors and the relative lack of tumor-killing cytotoxic T lymphocytes in invasive micropapillary carcinoma may explain, in part, the adverse association of tumor infiltrating lymphocytes with the biological behavior of invasive micropapillary carcinoma of breast.