Department of Surgery, St. George Hospital, University of New South Wales Kogarah, NSW 2217, Australia.
Am J Cancer Res. 2013 Aug 14;3(4):411-23. eCollection 2013.
malignant peritoneal mesothelioma (MPM) is a rare peritoneal mesothelial neoplasm. Ki67 and BCL2 are established prognostic markers in several cancers. High Ki67 expression indicates tumour progression, whilst similar expression of BCL2 retards tumour replication. Traditionally, prognosis in MPM is gauged with a single biomarker assessed separately in a dichotomous manner. Here, we examine prognosis with dual biomarkers incorporated in a model to predict survival.
Forty two MPM archival patient tumours were screened for Ki67 and BCL2 by immunohistochemistry and evaluated using standard methods. Ki67 and BCL2 expression was incorporated into a prognostic model to develop Ki67-BCL2 index. Using this index, three hazard groups were identified (high, medium and low risk). Kaplan-Meier survival analysis was performed to assess the significance of these hazard groups in the various clinicopathological categories.
In all clinicopathological categories, high risk group showed poor prognosis compared to low risk group (p = < 0.001). Compared to medium risk, high risk group carried poor prognosis in all tumours, females, epitheloid tumours, peritoneal cancer index (PCI) < 20, ≥ 20, age at diagnosis (AAD) < 60, and ≥ 60 years. Independent of the Ki67-BCL2 index, male, sarcomatoid, PCI ≥ 20 and AAD ≥ 60 were poor prognostic factors. High risk group was an independent poor prognostic factor in all tumours, males, females and age < 60 years. The distribution of high risk: low risk group in male and female was 3: 2 and 2: 3, respectively, indicating a gender difference. Comparing hazard ratios generated by Ki67-BCL2 index to that of either Ki67 or BCL2, as a single prognostic biomarker, there was a reduction of HR values.
Ki67-BCL2 index seems to suggest a more sensitive method of predicting prognosis. However, the current model needs further evaluation in an independent large cohort sample.
恶性腹膜间皮瘤(MPM)是一种罕见的腹膜间皮肿瘤。Ki67 和 BCL2 是几种癌症中确立的预后标志物。高 Ki67 表达表明肿瘤进展,而 BCL2 相似的表达则会减缓肿瘤复制。传统上,MPM 的预后是通过单独以二分法评估的单一生物标志物来衡量的。在这里,我们通过纳入模型中的双重生物标志物来检查预后,以预测生存。
通过免疫组织化学筛选了 42 例 MPM 存档患者肿瘤的 Ki67 和 BCL2,并使用标准方法进行了评估。Ki67 和 BCL2 表达被纳入预后模型以建立 Ki67-BCL2 指数。使用该指数,确定了三个危险组(高、中、低风险)。进行 Kaplan-Meier 生存分析以评估这些危险组在各种临床病理类别中的意义。
在所有临床病理类别中,与低风险组相比,高风险组的预后较差(p<0.001)。与中风险组相比,高风险组在所有肿瘤、女性、上皮样肿瘤、腹膜癌症指数(PCI)<20、≥20、诊断时年龄(AAD)<60 和≥60 岁中均预后较差。独立于 Ki67-BCL2 指数,男性、肉瘤样、PCI≥20 和 AAD≥60 是不良预后因素。在所有肿瘤、男性、女性和年龄<60 岁中,高风险组是独立的不良预后因素。在男性和女性中,高风险:低风险组的分布分别为 3:2 和 2:3,这表明存在性别差异。将 Ki67-BCL2 指数生成的危险比与 Ki67 或 BCL2 作为单一预后生物标志物生成的危险比进行比较,HR 值降低。
Ki67-BCL2 指数似乎表明了一种更敏感的预测预后的方法。然而,当前的模型需要在独立的大样本队列中进一步评估。