J Pathol Transl Med.  2015 Jan;49(1):30-36. 10.4132/jptm.2014.10.23.

Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors

• Son EM
• Kim JY
• An S
• Song KB
• Kim SC
• Yu E
• Hong SM

• KMID: 2381350
• DOI: http://doi.org/10.4132/jptm.2014.10.23

Abstract

BACKGROUND
Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients.
METHODS
To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors.
RESULTS
Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses.
CONCLUSIONS
CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

Keyword

Pancreas; Neuroendocrine tumors; Keratin-19; KIT; Immunohistochemistry

MeSH Terms

Biomarkers
Classification
Humans
Immunohistochemistry
Keratin-19*
Multivariate Analysis
Neoplasm Metastasis
Neuroendocrine Tumors*
Pancreas
Prognosis
Survival Rate
World Health Organization
Keratin-19

Figure

• 

  Fig. 1. Representative images of KIT and cytokeratin 19 (CK19) staining. (A) Normal acinar cell, ductal epithelial cells, and islet cells (arrows) of the pancreas are negative for KIT staining, while mast cells in the pancreatic parenchyma are positive for KIT staining. (B) Membranous CK19 immunolabeling is noted in the normal centroacinar cell and the ductal epithelial cells, while islet cells are not stained. Negative (C) and positive (D) KIT expression in a pancreatic neuroendocrine tumor. (E) Negative CK19 expression is observed in a pancreatic neuroendocrine tumor, while entrapped normal pancreatic ductal cells are positive for CK19. (F) Positive CK19 expression in a pancreatic neuroendocrine tumor.

• 

  Fig. 2. Kaplan-Meier survival analysis of pancreatic neuroendocrine tumor patients according to KIT (A) and cytokeratin 19 (CK19) (B) expression status. (A) The overall 5-year survival rate for pancreatic neuroendocrine tumor (PanNET) patients with KIT expression is significantly lower (62%) than that of patients without KIT expression (77%, p=.011). (B) The overall 5-year survival rate for PanNET patients with CK19 expression (74%) is not significantly different from that of those without CK19 expression (79%, p=.243).

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