增殖诱导配体在乳腺癌原发灶表达及与预后的关系

摘要

目的：探讨早期乳腺癌原发灶增殖诱导配体（A proliferation inducing ligand, APRIL）表达分布与预后的关系。方法回顾性收集2000年1月~2002年12月在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，用免疫组织化学法检测乳腺癌原发灶APRIL表达分布情况并分析其与CD8、CD4阳性淋巴细胞浸润强度的关系。分析APRIL表达分布情况与乳腺癌临床病理特征及预后的关系。结果在大部分病例均可观察到肿瘤细胞的细胞质、间质细胞及部分基质为APRIL染色阳性。APRIL肿瘤细胞质强度与APRIL阳性间质细胞密度正相关（P=0.009），与Ki67百分比正相关（P=0.003）。APRIL阳性间质细胞密度与CD4+间质细胞密度（P<0.001）和CD8+间质细胞密度（P<0.001）均正相关。在激素受体阴性（雌激素受体和孕激素受体均为阴性)患者，APRIL阳性间质细胞密度升高与较好的预后相关，是DFS（HR=0.313，95%CI=0.107-0.920，P=0.035）的独立保护性预后因素。结论乳腺癌间质免疫细胞广泛表达APRIL，乳腺癌细胞APRIL染色强度与肿瘤细胞的增殖正相关，提示免疫细胞可能通过分泌APRIL促进乳腺癌细胞增殖。在激素受体阴性患者，乳腺癌间质APRIL阳性细胞较多的患者预后较好。%Objective To explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor foci of breast cancer and the patients' prognosis. Methods Paraffin sections of surgical specimens were retrospectively collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial APRIL-positive cells, and their association was analyzed with the density of interstitial CD4+ and CD8+ cells and with the histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients. Results APRIL positive staining was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4+cells (P<0.001) and CD8+cells (P<0.001). In hormone receptor negative patients (ER-and PR-), multivariate COX regression identified the density of interstitial APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). Conclusions APRIL is widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.