非特殊型浸润性与伴髓样特征乳腺癌浸润淋巴细胞和细胞因子表达差异对预后影响研究

Relationship between infiltrating lymphocytes and cytokines of tumors and prognosis of invasive breast carcinoma of no specific type and cacinoma with medullary features patients

目的肿瘤生长的微环境影响其生物学行为,乳腺癌中肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TILs)的评估与临床关系日益密切。本研究探讨非特殊型浸润性乳腺癌(invasive breast carcinoma of no specific type,IBC-NST)与伴髓样特征癌中,TILs、白细胞介素-2(interleukin-2,IL-2)和淋巴毒素α(lymphotoxinα,LTα)表达差异及与预后的关系。方法选取河北医科大学第四医院2006-01-01-2010-12-30原发性乳腺癌手术切除标本242例,其中IBC-NST 152例,伴髓样特征癌90例。采用免疫组化HRP法检测两种乳腺癌中T淋巴细胞及其亚群、B淋巴细胞、自然杀伤细胞(natural killer cell,NK)和细胞因子表达及与预后的关系。结果与伴髓样特征癌组相比,IBC-NST组淋巴结转移率和脉管瘤栓阳性率均较高,临床分期较晚,差异有统计学意义,P<0.05。CD3、CD4、CD8、CD20、CD57及细胞因子IL-2、LTα,在伴髓样特征癌组的表达均高于IBC-NST组,均P<0.001。伴髓样特征癌组TILs表达为CD3表达最高,CD20细胞次之,CD57细胞表达最低,均P<0.05;且伴髓样特征癌组中CD8表达高于CD4,P<0.001。细胞因子IL-2和LTα在伴髓样特征癌组阳性率分别为87.8%和88.9%,高于IBC-NST组的68.4%和85.5%,均P<0.001。伴髓样特征癌组患者5年生存率为95.6%,高于IBC-NST组的87.4%,P=0.038。CD8与伴髓样特征癌组预后呈正相关,P<0.05。结论与IBC-NST相比,伴髓样特征癌中浸润性T、B、NK淋巴细胞较多且是其预后较好重要原因之一,其中T细胞特别是CD8+T细胞发挥了重要作用。

OBJECTIVE The microenvironment of tumor growth influences its biological behavior.The assessment of tumor infiltrating lymphocyte（TIL）in breast cancer is closely related to the clinic.This study to investigate the expression of tumor infiltrating lymphocytes,cytokines Interleukin-2（IL-2）and Lymphotoxinα（LTα）in invasive breast carcinoma of no specific type（IBC-NST）and the carcinomas with medullary features,and analyze the relationship with the prognosis.METHODS Data of 242 cases obtained from the Fourth Hospital of Hebei Medical University between 2006-01-01 and 2010-12-30 was retrospectively analyzed,including 152 invasive carcinoma of no specific type（IBC-NST）cases and 90 cacinoma with medullary features cases.The expression of T lymphocytes and their subpopulations,B lymphocytes,natural killer cells（NKs）and cytokines（IL-2,LTα）were evaluated by HRP immunohistochemistry method and their relationship with prognosis were analyzed.RESULTS Compared with the myeloid-like carcinoma group,the lymph node metastasis rate and vascular tumor embolus positive rate were higher,and the clinical staging was later in IBC-NST group,the difference was statistically significant,P〈0.05.The expression of CD3,CD4,CD8,CD20,CD57,IL-2,LTαand in carcinoma with medullary features group were all higher than that in IBC-NST group（P〈0.05）.In carcinoma with medullary features group,the expression of CD3 was the highest,followed by CD20,the lowest in CD57（P〈0.05）.The expression of CD8 was higher than CD4 in carcinomas with medullary features group（P〈0.01）.The positive rates of IL-2 and LTαin the carcinomas with medullary features group were 87.8% and 88.9% higher than that in the IBC-NST group（68.4%and 85.5%）.The difference was statistically significant（Theχ^2 values were 44.334 and 18.270,P〈0.001）.The 5-year survival rate of Carcinoma with medullary features group（95.6%）was higher than that of IBC-NST group（87.4%）（P=0.038）.The expression of CD8 was positively correlated with the prognosis of Carcinoma with medullary features group（P〈0.05）.CONCLUSIONS The prognosis of carcinoma with medullary features group was better than that of IBC-NST group and may have relationship with the infiltrating T,B and NK cells,and especially T cells and Tc cells may play an important role.