Cancer Res Treat.  2011 Sep;43(3):181-188.

Clinical Significance of Protein Expression of Cyclooxygenase-2 and Somatostatin Receptors in Gastroenteropancreatic Neuroendocrine Tumors

• Kim HS
• Lee HS
• Kim WH

Abstract

PURPOSE
This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
MATERIALS AND METHODS
Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5.
RESULTS
COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001).
CONCLUSION
Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.

Keyword

Cyclooxygenase-2; Somatostatin receptors; Neuroendocrine tumors

MeSH Terms

Chromogranin A
Cyclooxygenase 2
Humans
Immunohistochemistry
Liver
Multivariate Analysis
Neuroendocrine Tumors
Prognosis
Receptors, Somatostatin
Retrospective Studies
Somatostatin
Chromogranin A
Cyclooxygenase 2
Receptors, Somatostatin
Somatostatin

Figure

• 

  Fig. 1 Immunostaining results of gastroenteropancreatic neuroendocrine tumors for cyclooxygenase-2 (COX2), Ki-67, and somatostatin receptors (SSTRs) 1, 2, and 5. In neuroendocrine tumors, COX2 and SSTR5 are localized in the cytoplasm, Ki-67 and SSTR1 are in the nuclei, and SSTR2 is in the membrane. First column, negative; second column, moderate positive; third column, strong positive; fourth column, high power field of strong positive (immunohistochemical staining with DAB, first three columns,×200; fourth column,×400).

• 

  Fig. 2 Kaplan-Meier analyses of overall survival in 194 patients with gastroenteropancreatic neuroendocrine tumors. (A) Cyclooxygenase-2: solid line, no overexpression; dotted line, overexpression. (B) Ki-67: solid line, G1; dotted line, G2 or G3. (C) Somatostatin receptor 2: solid line, positive; dotted line, negative.

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