Han Xu, Zhao Jing, Ji Yuan, Xu Xuefeng, Lou Wenhui
Department of Pancreatic Surgery, ZhongShan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Tumour Biol. 2013 Oct;34(5):2881-9. doi: 10.1007/s13277-013-0850-8. Epub 2013 May 19.
The objectives of this study were to validate the immunohistochemical expression patterns of CK19 and KIT in primary pancreatic neuroendocrine tumors (pNETs) and to verify the potential biomarkers that can be used to predict the clinical behaviors and postoperative outcomes. The immunohistochemical expressions of CK19 and KIT were determined in normal pancreatic islets and resectable pNETs. Associations of the immunohistochemical features with the clinicopathologic features and prognosis were evaluated. All 20 samples from the normal control group were negative for both KIT and CK19 in normal pancreatic islets. Positive rates for KIT and CK19 in pNETs were 49.5 % (45/91) and 70.0 % (70/100), respectively. The percentages of G1, G2, and G3 tumors were 54.9, 42.9, and 2.2 %, respectively. Ki-67 index was significantly higher in the KIT-positive subgroup than in the KIT-negative subgroup (p < 0.05); however, no statistically significant difference of the Ki-67 index was found between the CK19-positive and the CK19-negative subgroups (p = 0.656). The positive CK19 expression was significantly associated with non-functioning tumors, regional lymph nodes metastases, and advanced tumor node metastasis (TNM) stage (p < 0.05). Meanwhile, the positive KIT expression was significantly associated with advanced TNM grade (p < 0.05). In univariate analysis, the overall survival in patients with positive CK19 expression was significantly lower than that in patients with CK19-negative expression (p < 0.05). Also, patients with negative KIT expression showed a tendency of longer survival duration compared with those with positive KIT expression (p = 0.188). The high-risk subgroup (2.1 ± 2.9) might have a higher Ki-67 index than the low-risk subgroup (1.0 ± 1.7, p = 0.208). There was a significant difference in functioning status among the three risk levels (p < 0.05). Pairwise comparison prompted that patients at high risk were more prone to have regional lymph nodes metastases, distant metastases, and/or recurrences. In conclusion, the expressions of CK19 and KIT are associated with aggressive clinical behaviors in patients with resectable pNETs. CK19 and KIT may play a role in tumor progression and metastases.
本研究的目的是验证细胞角蛋白19（CK19）和原癌基因c-KIT在原发性胰腺神经内分泌肿瘤（pNETs）中的免疫组化表达模式，并验证可用于预测临床行为和术后结局的潜在生物标志物。在正常胰岛和可切除的pNETs中测定CK19和c-KIT的免疫组化表达。评估免疫组化特征与临床病理特征及预后的相关性。正常对照组的所有20个样本在正常胰岛中c-KIT和CK19均为阴性。pNETs中c-KIT和CK19的阳性率分别为49.5%（45/91）和70.0%（70/100）。G1、G2和G3级肿瘤的百分比分别为54.9%、42.9%和2.2%。c-KIT阳性亚组的Ki-67指数显著高于c-KIT阴性亚组（p<0.05）；然而，CK19阳性亚组和CK19阴性亚组之间的Ki-67指数差异无统计学意义（p=0.656）。CK19阳性表达与无功能性肿瘤、区域淋巴结转移及晚期肿瘤淋巴结转移（TNM）分期显著相关（p<0.05）。同时，c-KIT阳性表达与晚期TNM分级显著相关（p<0.05）。单因素分析显示，CK19阳性表达患者的总生存期显著低于CK19阴性表达患者（p<0.05）。此外，与c-KIT阳性表达患者相比，c-KIT阴性表达患者的生存时间有延长趋势（p=0.188）。高风险亚组（2.1±2.9）的Ki-67指数可能高于低风险亚组（1.0±1.7，p=0.208）。三个风险水平的功能状态存在显著差异（p<0.05）。两两比较提示，高风险患者更容易发生区域淋巴结转移、远处转移和/或复发。总之，CK19和c-KIT的表达与可切除pNETs患者的侵袭性临床行为相关。CK19和c-KIT可能在肿瘤进展和转移中起作用。
