title: Expression of CK19 and KIT in resectable pancreatic neuroendocrine tumors.
abstract: 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.
authors.affiliation: Department of Pancreatic Surgery, ZhongShan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xu
authors.forename: Wenhui
authors.initials: W
authors.lastname: Lou
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19; D019009:Proto-Oncogene Proteins c-kit