乳腺癌原发灶T淋巴细胞浸润与预后的关系

Prognostic Value of T Lymphocytes Infiltration in Breast Cancer

目的探讨Ⅰ～Ⅲ期乳腺癌原发灶中T淋巴细胞与临床病理特征以及预后的关系。方法回顾性收集2000年1月至2002年12月解放军总医院手术的130例Ⅰ～Ⅲ期乳腺癌患者的临床资料及石蜡切片,用免疫组织化学方法检测乳腺癌原发灶中CD4+和CD8+淋巴细胞浸润强度并分析其与乳腺癌临床病理特征及预后的关系。结果 CD4+细胞癌巢浸润在COX多元分析中是无病生存(HR=0.248,95%CI=0.113-0.543,P=0.000)、远处无转移生存(DDFS)(HR=0.361,95%CI=0.157-0.830,P=0.017)、总生存(OS)(HR=0.297,95%CI=0.119-0.741,P=0.009)的独立预后因素,与较好预后相关。CD8+间质细胞密度和CD8+细胞癌巢浸润在激素受体阴性(雌激素受体和孕激素受体均为阴性)患者分别是OS(HR=0.286,95%CI=0.101-0.807,P=0.018)和DDFS(HR=0.293,95%CI=0.104-0.825,P=0.020)的独立预后因素,均与较好的预后相关。CD8+间质细胞密度和CD8+细胞癌巢浸润在激素受体阳性(雌激素受体和孕激素受体至少1个阳性)患者分别是OS(HR=4.854,95%CI=1.435-16.415,P=0.011)和DDFS(HR=10.493,95%CI=1.226-89.795,P=0.032)的独立预后因素,均与较差的预后相关。在激素受体阳性患者,术后辅助内分泌治疗可显著改善CD8+间质细胞密度低患者的OS。结论乳腺癌原发灶CD4+细胞癌巢浸润与较好的预后相关。乳腺癌原发灶CD8+间质细胞密度和CD8+细胞癌巢浸润在激素受体阴性患者与较好的预后相关,但在激素受体阳性患者与较差的预后相关。术后辅助内分泌治疗的远期疗效与乳腺癌原发灶CD8+间质细胞密度相关,进而影响CD8+细胞与乳腺癌预后的关系。以上结论为探索免疫相关的乳腺癌预后指标提供了线索。

Objective To assess and compare the prognostic role of tumor-infiltrating T lymphocytes in stage Ⅰ-Ⅲ breast cancer. Methods Paraffin sections were retrospectively collected from 130 cases of stage Ⅰ-Ⅲ breast cancer patients who received surgery between January 2000 and December 2002 in General Hospital of the People＇ s Liberation Army. Immunohistochemistry was used to assess the density of tumor-infiltrating lym- phocytes （TILs） that were positive of CD4 and CDS. These variables were evaluated for their association with histopathologic features along with overall survival （OS）, distant disease-free survival （DDFS） and disease-free survival （DFS）. Results Intraepithelial CD4 ＋ lymphocytes infiltration was an independent prognostic fac- tor for DFS （ HR = 0. 248, 95% CI = 0. 113-0. 543, P = 0. 000）, DDFS （HR = 0. 361, 95% CI = O. 157- 0. 830, P = 0. 017）, and OS （HR = 0. 297, 95 % CI = 0. 119-0. 741, P = 0. 009） in multifactor COX regres- sion model. In hormone receptor negative group, mesenchymal CD8 ＋ lymphocytes and intraepithelial CD8 ＋ lym- phocytes were independent prognostic factors for OS （HR = 0. 286, 95% CI = 0. 101-0. 807, P = 0. 018 ） and DDFS （HR =0. 293, 95% CI =0. 104-0. 825, P =0. 020） , respectively. In hormone receptor positive group, mesenehymal CD8 ＋ lymphocytes and intraepithelial CD8 ＋ lymphocytes were independent prognostic factors for OS （HR = 4.854, 95% CI = 1.435-16.415, P = 0.011） and DDFS （HR = 10.493, 95% CI = 1.226- 89. 795, P = 0. 032） respectively. Further analysis found that OS of hormone receptor positive patients with low- er mesenchymal CD8 ＋ TILs was significantly proved by adjuvant endocrine therapy. Conclusions In the current investigation, intraepithelial CD4 ＋ TILs demonstrated independent prognostic significance for survival. CD8 ＋ TILs were associated with better survival in hormone receptor negative patients but associated with worse survival in hormone receptor positive patients. The long-term clinical effects of adjuvant endocrine therapy is related with density of mesenehymal CD8 ＋ TILs and in turn affected prognostic value of mesenchymal CD8 ＋ TILs.