ORIGINAL ARTICLE

COX-2 expression in ampullary carcinoma: correlation with angiogenesis process and clinicopathological variables

G Perrone¹, D Santini², A Verzì¹, B Vincenzi², D Borzomati³, F Vecchio⁴, R Coppola³, A Antinori⁵, P Magistrelli⁵, G Tonini², C Rabitti¹

¹ Surgical Pathology, Campus Bio-Medico University, Rome, Italy
² Oncology Unit, Campus Bio-Medico University, Rome, Italy
³ General Surgery Department, Campus Bio-Medico University, Rome, Italy
⁴ Anatomic Pathology And Histology, Catholic University of Sacred Heart, Rome, Italy
⁵ General Surgery Department, Catholic University of the Sacred Heart, Rome, Italy

Correspondence to:
Dr Giuseppe Perrone
Surgical Pathology, Campus Bio-Medico University, Via Emilio Longoni 83, 00155 Rome, Italy; g.perrone{at}unicampus.it

Background: There is evidence that the anti-neoplastic effect of non-steroidal anti-inflammatory drugs is attributable to cyclooxygenase-2 (COX-2) inhibition, but the exact mechanisms whereby COX-2 can promote tumour cell growth remain unclear. One hypothesis is the stimulation of tumour angiogenesis by the products of COX-2 activity. To data, there have been few clinicopathological studies on COX-2 expression in human ampullary carcinoma and no data have been reported about its relation with tumour angiogenesis.

Objective: To investigate by immunohistochemistry the expression of COX-2 and the angiogenesis process in a series of primary untreated ampullary carcinomas.

Methods: Tissue samples from 40 archival ampullary carcinomas were analysed for COX-2, vascular endothelial growth factor (VEGF), and an endothelial cell marker von Willebrand factor (vWF) by immunohistochemistry, using specific antibodies.

Results: COX-2 expression was detected in 39 tissue samples (97.5%), of which two (5%) were graded as weak, 26 (65%) as moderate, and 11 (27.5%) as strong. Only one lesion (2.5%) was negative for COX-2 expression. VEGF expression was detected in 36 tissue samples (90%). A significant positive correlation was found between COX-2 and VEGF expression. No statistic correlation was found between COX-2 expression and microvessel density.

Conclusions: COX-2 is highly expressed in ampullary carcinomas. This suggests an involvement of the COX-2 pathway in ampullary tumour associated angiogenesis, providing a rationale for targeting COX-2 in the treatment of ampullary cancer.

Abbreviations: COX-2, cyclooxygenase-2; HIF, hypoxia inducible factor; HIS, immunohistochemical score; IQR, interquartile range; MVD, microvessel density; PGE2, prostaglandin E2; VEGF, vascular endothelial growth factor; vWF, von Willebrand factor

Keywords: ampullary carcinoma; angiogenesis; COX-2; VEGF; microvessel density

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