Yu Hai-ming, Jiao Shun-chang, Yang Jun-lan, Wang Jian-dong
Department of Medical Oncology, General Hospital of the People's Liberation Army, Beijing, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2013 Apr;35(2):199-206. doi: 10.3881/j.issn.1000-503X.2013.02.013.
To assess and compare the prognostic role of tumor-infiltrating T lymphocytes in stage 1-3 breast cancer.
Paraffin sections were retrospectively collected from 130 cases of stage 1-3 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 lymphocytes(TILs) that were positive of CD4 and CD8. 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) .
Intraepithelial CD4+lymphocytes infiltration was an independent prognostic factor for DFS(HR=0.248, 95%CI=0.113-0.543, P=0.000) , DDFS(HR=0.361, 95%CI=0.157-0.830, P=0.017) , and OS(HR=0.297, 95%CI=0.119-0.741, P=0.009) in multifactor COX regression model. In hormone receptor negative group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes 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, mesenchymal 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 lower mesenchymal CD8+TILs was significantly proved by adjuvant endocrine therapy.
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 mesenchymal CD8+TILs and in turn affected prognostic value of mesenchymal CD8+TILs.
评估并比较肿瘤浸润性T淋巴细胞在1-3期乳腺癌中的预后作用。
回顾性收集2000年1月至2002年12月期间在解放军总医院接受手术的130例1-3期乳腺癌患者的石蜡切片。采用免疫组织化学方法评估CD4和CD8阳性的肿瘤浸润淋巴细胞(TILs)密度。评估这些变量与组织病理学特征以及总生存期(OS)、远处无病生存期(DDFS)和无病生存期(DFS)的相关性。
在多因素COX回归模型中,上皮内CD4+淋巴细胞浸润是DFS(HR=0.248,95%CI=0.113-0.543,P=0.000)、DDFS(HR=0.361,95%CI=0.157-0.830,P=0.017)和OS(HR=0.297,95%CI=0.119-0.741,P=0.009)的独立预后因素。在激素受体阴性组中,间质CD8+淋巴细胞和上皮内CD8+淋巴细胞分别是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。在激素受体阳性组中,间质CD8+淋巴细胞和上皮内CD8+淋巴细胞分别是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。进一步分析发现,辅助内分泌治疗显著改善了间质CD8+TILs较低的激素受体阳性患者的OS。
在本研究中,上皮内CD4+TILs对生存具有独立的预后意义。CD8+TILs在激素受体阴性患者中与较好的生存相关,但在激素受体阳性患者中与较差的生存相关。辅助内分泌治疗长期临床疗效与间质CD8+TILs密度有关,进而影响间质CD8+TILs的预后价值。