Chang Hee Jin, Yoo Byong Chul, Kim Sun Whe, Lee Byung Lan, Kim Woo Ho
Research Institute and Hospital, National Cancer Center, Seoul, Korea.
Pathol Oncol Res. 2007;13(4):326-35. doi: 10.1007/BF02940312. Epub 2007 Dec 25.
Molecular markers for cancers are not only useful for cancer detection and prognostic prediction, but may also serve as potential therapeutic targets. In order to identify reliable molecular markers for prognostic prediction in gallbladder carcinoma (GBC), we evaluated the immunohistochemical expression of 15 proteins, namely p53, p27, p16, RB, Smad4, PTEN, FHIT, GSTP1, MGMT, E-cadherin, nm23, CD44, TIMP3, S100A4, and promyelocytic leukemia (PML) in 138 cases of GBC using the tissue microarray method. The prognostic significance was analyzed for each protein. Overexpression of p53 and S100A4, and loss of p27, p16, RB, Smad4, FHIT, E-cadherin and PML expression were associated with poor survival. In particular, PML and p53 showed considerable potential as independent prognostic markers. Patients with normal PML and p53 expression displayed favorable outcomes, compared to those showing abnormal expression of either or both proteins (49% vs. 23% in a 5-year survival rate; 60 months vs. 11 months in median survival, respectively; P=0.009). Thus, PML and p53 are potential candidates for development as clinically applicable molecular prognostic markers of GBC, and may be effective therapeutic targets for the disease in the future.
癌症分子标志物不仅有助于癌症检测和预后预测，还可能作为潜在的治疗靶点。为了确定胆囊癌（GBC）预后预测的可靠分子标志物，我们采用组织芯片方法评估了138例GBC病例中15种蛋白质的免疫组化表达，这些蛋白质分别为p53、p27、p16、RB、Smad4、PTEN、FHIT、GSTP1、MGMT、E-钙黏蛋白、nm23、CD44、TIMP3、S100A4和早幼粒细胞白血病（PML）。分析了每种蛋白质的预后意义。p53和S100A4的过表达以及p27、p16、RB、Smad4、FHIT、E-钙黏蛋白和PML表达的缺失与不良生存相关。特别是，PML和p53显示出作为独立预后标志物的巨大潜力。与PML和p53表达异常（一种或两种蛋白异常）的患者相比，PML和p53表达正常的患者预后良好（5年生存率分别为49%和23%；中位生存期分别为60个月和11个月；P=0.009）。因此，PML和p5可能是开发为GBC临床适用分子预后标志物的潜在候选物，并且未来可能是该疾病的有效治疗靶点。
