Mühlmann G, Spizzo G, Gostner J, Zitt M, Maier H, Moser P, Gastl G, Zitt M, Müller H M, Margreiter R, Ofner D, Fong D
Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Austria.
J Clin Pathol. 2009 Feb;62(2):152-8. doi: 10.1136/jcp.2008.060590. Epub 2008 Oct 17.
In gastric cancer the recurrence rate is unacceptably high, even after R0 resection and (neo)adjuvant chemotherapy. Therefore, there is an urgent need for identification of predictive and/or prognostic biomarkers to select high-risk patients who might benefit from additional therapies. Expression of TROP2 has been shown to be associated with tumour aggressiveness and poor prognosis in patients with various epithelial cancers.
To investigate TROP2 expression in gastric cancer and its correlation with clinicopathological features and disease outcome.
Expression of TROP2 was investigated by immunohistochemistry of tumour specimens from 104 patients who underwent resection for gastric cancer. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model.
TROP2 was found to be overexpressed in 58 (56%) tumour samples. Significantly higher expression of TROP2 could be detected in intestinal-type carcinomas (p = 0.03). In intestinal-type gastric cancer, TROP2 overexpression was significantly correlated with shorter disease-free survival (DFS) (p = 0.03). Among the total group, TROP2 overexpression was predictive for poor disease-free (p<0.01) and overall (p = 0.03) survival in lymph node positive patients. Multivariate Cox regression analysis revealed TROP2 overexpression to be an independent prognostic marker for poor DFS in the subgroup of patients with intestinal-type gastric cancer irrespective of lymph node involvement.
Results show that TROP2 is an independent prognostic marker for disease recurrence in intestinal type gastric cancer. Due to its wide distribution TROP2 may become an attractive therapeutic target in a subgroup of patients with gastric cancer.
在胃癌中,即使经过R0切除和(新)辅助化疗,复发率仍高得令人难以接受。因此,迫切需要识别预测性和/或预后性生物标志物,以筛选可能从额外治疗中获益的高危患者。已表明TROP2的表达与多种上皮癌患者的肿瘤侵袭性和不良预后相关。
研究TROP2在胃癌中的表达及其与临床病理特征和疾病转归的相关性。
通过免疫组织化学检测104例行胃癌切除术患者的肿瘤标本中TROP2的表达。在单变量分析中发现具有预后意义的参数在多变量Cox回归模型中进行验证。
在58份(56%)肿瘤样本中发现TROP2过表达。在肠型癌中可检测到TROP2表达显著更高(p = 0.03)。在肠型胃癌中,TROP2过表达与无病生存期(DFS)较短显著相关(p = 0.03)。在整个队列中,TROP2过表达可预测淋巴结阳性患者的无病生存期差(p<0.01)和总生存期差(p = 0.03)。多变量Cox回归分析显示,无论淋巴结是否受累,TROP2过表达都是肠型胃癌患者DFS差的独立预后标志物。
结果表明,TROP2是肠型胃癌疾病复发的独立预后标志物。由于其广泛分布,TROP2可能成为一部分胃癌患者有吸引力的治疗靶点。