Ulukus Emine Cagnur, Kargi H Aydanur, Sis Banu, Lebe Banu, Oztop Ilhan, Akkoclu Atilla, Onen Ahmet, Sanli Aydin
Department of Pathology, Dokuz Eylul University School of Medicine, 35340 Inciralti, Izmir, Turkey.
Appl Immunohistochem Mol Morphol. 2007 Mar;15(1):31-7. doi: 10.1097/01.pai.0000201808.35931.78.
The role of survivin that regulates the biological behavior of non-small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin expression in NSCLC and to define any correlation with expressions of p53, bcl-2, bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables, and overall survival. Tumors of 63 patients with NSCLC were examined for expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI was also evaluated. Results for each antibody were correlated with each other, and with clinicopathologic variables including age, sex, histologic subtype, TNM (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis) stage, lymph node status, smoking history, and prognosis. Nuclear survivin expression was inversely correlated with p53 expression (P = 0.04, r = - 0.367), and tumor stage (P = 0.03, r = - 0.273), and positively correlated with tumor cell proliferation (P = 0.009, r = 0.329). Cytoplasmic survivin expression positively correlated with smoking history (P = 0.02, r = 0.282). Survivin/bax ratio was inversely correlated with AI (r: - 0.004). By Kaplan-Meier analysis, TNM stage (P < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P < or = 0.001) were associated with survival, whereas survivin was not. In multivariate analysis, only TNM stage was an independent predictor. Although survivin and other apoptosis-related protein expressions fail to predict the clinical outcome, the present findings suggest that survivin is involved in tumor cell apoptosis and proliferation and may play a role in critical steps of cancer progression in NSCLC.
生存素在调节非小细胞肺癌(NSCLC)生物学行为中的作用仍存在争议。我们旨在研究NSCLC中生存素的表达情况,并确定其与p53、bcl-2、bax、凋亡指数(AI)、肿瘤细胞增殖、临床病理变量及总生存率之间的相关性。采用免疫组织化学方法检测63例NSCLC患者肿瘤组织中生存素、p53、bcl-2、bax及Ki-67的表达情况,并评估AI。分析各抗体检测结果之间以及与年龄、性别、组织学亚型、TNM(T:原发肿瘤,N:区域淋巴结转移,M:远处转移)分期、淋巴结状态、吸烟史和预后等临床病理变量之间的相关性。细胞核生存素表达与p53表达呈负相关(P = 0.04,r = - 0.367),与肿瘤分期呈负相关(P = 0.03,r = - 0.273),与肿瘤细胞增殖呈正相关(P = 0.009,r = 0.329)。细胞质生存素表达与吸烟史呈正相关(P = 0.02,r = 0.282)。生存素/bax比值与AI呈负相关(r: - 0.004)。通过Kaplan-Meier分析,TNM分期(P≤0.001)、淋巴结转移(P = 0.04)和Ki-67指数(P≤0.001)与生存率相关,而生存素与生存率无关。多因素分析显示,只有TNM分期是独立的预后预测因素。尽管生存素及其他凋亡相关蛋白表达不能预测临床结局,但本研究结果提示生存素参与肿瘤细胞凋亡和增殖过程,可能在NSCLC癌症进展的关键步骤中发挥作用。