Baekelandt M, Holm R, Nesland J M, Tropé C G, Kristensen G B
Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo, Norway.
J Clin Oncol. 2000 Nov 15;18(22):3775-81. doi: 10.1200/JCO.2000.18.22.3775.
The present study was undertaken to investigate the prognostic and predictive relevance of the expression of apoptosis-related proteins Bax, Bcl-X(L), and Mcl-1 in advanced ovarian cancer.
Tumor biopsies from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for the expression of Bax, Bcl-X(L) and Mcl-1 proteins. Their prognostic relevance was examined in a uni- and multivariate survival analysis.
Sixty-six percent of cancer cases expressed Bax, 62% Bcl-X(L), and 53% Mcl-1. The expression of Bax correlated with tumor differentiation (P: =.016) and less residual disease after surgery (P <.0001). In univariate analysis, Bax expression was associated with improved (P =.0004) prognosis and Mcl-1 expression with poorer (P =.011) prognosis. None of the factors studied was of independent prognostic significance by itself, but when Bax and Bcl-2 expression data were considered together, this combined variable was of independent prognostic significance (P =.0115), together with residual disease status (P =.0016), differentiation grade (P =.0014), and the presence of ascites (P =.0122). Patients with a long median survival (104 months) could be discriminated from those with a short one (16 months) by combining the individual patients' expression data for p53, Bax, and Bcl-2 with their residual disease status (P <.00001). None of the factors studied was able to predict response to chemotherapy.
The expression of selected apoptosis-related proteins is of independent prognostic significance and may be helpful in a molecular substaging of patients with stage III ovarian cancer.
本研究旨在探讨凋亡相关蛋白Bax、Bcl-X(L)和Mcl-1的表达在晚期卵巢癌中的预后及预测相关性。
对185例连续接受相同治疗的III期卵巢癌患者的肿瘤活检组织进行免疫组化检查，以检测Bax、Bcl-X(L)和Mcl-1蛋白的表达。通过单因素和多因素生存分析来检验它们的预后相关性。
66%的癌症病例表达Bax，62%表达Bcl-X(L)，53%表达Mcl-1。Bax的表达与肿瘤分化相关（P = 0.016），且与术后残留病灶较少相关（P < 0.0001）。在单因素分析中，Bax表达与预后改善相关（P = 0.0004），Mcl-1表达与预后较差相关（P = 0.011）。所研究的因素本身均无独立的预后意义，但当将Bax和Bcl-2表达数据综合考虑时，这一联合变量具有独立的预后意义（P = 0.0115），同时还有残留病灶状态（P = 0.0016）、分化程度（P = 0.0014）和腹水的存在（P = 0.0122）。通过将个体患者的p53、Bax和Bcl-2表达数据与其残留病灶状态相结合（P < 0.00001），可将中位生存期长（104个月）的患者与中位生存期短（16个月）的患者区分开来。所研究的因素均无法预测化疗反应。
所选凋亡相关蛋白的表达具有独立的预后意义，可能有助于对III期卵巢癌患者进行分子分期。
