乳腺癌原发灶及腋窝淋巴结中细胞毒性淋巴细胞与临床病理的关系

Cfinicopathological significance of cytotoxic lymphocytes in breast cancer and draining lymph nodes

目的分析乳腺癌原发灶组织和腋淋巴结中细胞毒性淋巴细胞的数量和状态，并与乳腺癌临床病理特征相比较，探讨其意义。方法对资料齐全且术前均未接受任何化疗和放疗的74例乳腺癌原发灶及所切除的腋淋巴结进行病理分型及临床病理分期，并分为淋巴结无转移组和有转移组。采用免疫组织化学催化信号放大系统和EnVision法，通过单克隆抗体CD8、粒酶B、穿孔素、CD56的检测，分析肿瘤原发灶及腋淋巴结中细胞毒性淋巴细胞的表型和功能。结果在肿瘤原发灶组织中CD8^＋细胞间质明显多于实质，淋巴结无转移组肿瘤局部[（35．7±16．0）个]及腋淋巴结CD8^＋细．胞数[（53．0±18．2）个]均高于淋巴结有转移组[（23．7±9．6）个和（38．2±12．7）个]，肿瘤原发灶CD8^＋细胞数在5年生存组[（32．9±14．1）个]显著高于死亡组[（20．1±9．9）个]。以粒酶B为细胞毒性淋巴细胞活化标记时，细胞毒性淋巴细胞的百分率差异无统计学意义；肿瘤组织和腋淋巴结中CD8^＋、CD56^＋细胞数均与临床病理分期无关。与Ⅰ期相比，在Ⅲ＋Ⅳ期原发灶组织和腋淋巴结中细胞毒性淋巴细胞的数量显著降低。值得注意的是，在多数情况下，原发灶组织中穿孔素＋细胞数量明显低于粒酶B＋细胞。结论在乳腺癌中细胞毒性淋巴细胞对抑制其肿瘤转移、提高患者生存率有一定意义。组织中细胞毒性淋巴细胞功能缺陷可能是影响其发挥抗瘤效应的重要因素。

Objective To analyze retrospectively the quantity and activation status of the tumor infiltrating cytotoxic lymphocytes in breast cancer and the draining lymph nodes, and its relation to the clinical pathological significance. Methods Seventy-four breast cancer samples with their corresponding axillary lymph nodes were histologically typed and staged. Cytotxic lymphocytes were analyzed by immunohistochemistry with the monoclonal antibodies against CD8, CD56, granzyme B and perforin. Results The number of infiltrating CD8^＋ T cells in the cancerous interstitial tissue were much higher than that in the tumor parenchyma. Compared with the metastatic tumor samples, the CD8^＋ T cells were more intensive in the primary tumors （ 35.7 ± 16. 0 vs. 23.7± 9. 6 ）. The tumor infiltrating CD8^＋ T cells of patients with 5 years survivals were more than that of the dead cases in this follow-up series death （ 32. 9 ± 14. 1 vs. 20. 1 ± 9. 9 ）. There was no significant difference of activated tumor infiltrating cytotoxic T cell analyzed by using the activation marker granzyme B ＋ and there was also no significant correlation between the intensity of CD8^＋ , CD56^＋ cells and the clinicopathological stages. However, percentages of the activated eytotoxic lymphoeytes in Stage Ⅰ groups were significantly higher than those in stage Ⅲ and Ⅳ. Moreover, the number of perforin ＋ cells was significantly less than that of granzyme B ＋ cells, particularly in the cancerous tissue, indicating a dysfunctional status of tumor infiltrating eytotoxic lymphocytes. Conclusions Activated cytotoxic lymphocytes may play a significant role against the tumor progression and is associated with a favorable prognosis to some extent. However, a putative dysfunctional status of cytotoxic lymphocytes at tumor site may compromise the host immunity against cancer.