Expression of cyclooxygenase-2 (COX-2) in pituitary tumours

Abstract

Background: Microvessel density in angiogenesis is regarded as a prognostic factor of tumour invasiveness, independent of cell proliferation. In recent studies of pituitary tumours, correlation between the expression of cyclooxygenase-2 (COX-2) and micro-vascularization density and microvessel surface density has been established. We studied the expression of COX-2 in different types of pituitary adenomas to determine the usefulness of COX-2 expression as a prognostic factor of tumour progression or recurrence in patients with hypophyseal tumours.

Material/methods: We retrospectively studied a group of 60 patients of mean age 46.7±17.6 (range, 18 to 85) years who underwent pituitary tumour surgery. Expression of COX-2, as determined by immunohistochemistry, was analyzed in relation to histopathology features of tumour, clinical symptoms, MR imaging and post-operative recurrence/progression of disease.

Results: COX-2 was expressed in adenomas of 87% of patients, with a median index value of 57.5% [IQR=60.5]. Highest COX-2 expression was observed in hormonally inactive adenomas and gonadotropinomas and lowest in prolactinomas. We found no differences in COX-2 expression with respect to patient age, gender, tumour size, degree of tumour invasiveness, or whether tumours were immunopositive or immunonegative for pituitary hormones, nor have we found any relation between COX-2 expression and recurrence or progression of tumour size.

Conclusions: COX-2 does not appear to be a predictive factor for recurrence or progression of tumour size. Nevertheless, due to the observed relatively high expression of COX-2 in pituitary adenomas, further studies with COX-2 inhibitors are justified in these tumours.

Figure 1

Kaplan-Maier plots of MRI-observed recurrence/progression of pituitary adenoma against COX-2 index in patients of the studied group (n=60); (A) grouped with respect to values of COX-2 index: COX-2 index =0% (n=2/8 patients, 25.0%); 0% <COX-2 index ≤35% (n=4/14 patients, 28.6%); 35% <COX-2 index ≤70%(n=6/16 patients, 37.5%); 70% <COX-2 index ≤100% (n=10/22 patients, 45.5%); (B) grouped with respect to COX-2 index ≤ median (n=10/30 patients, 33.3%); COX-2 index > median (n=12/30 patients, 40.0%)

Figure 2

Kaplan-Maier plots of hormone secretion recurrence of pituitary adenoma against COX-2 index in patients of the studied group (n=60); (A) grouped with respect to values of COX-2 index: COX-2 index =0% (n=3/8 patients, 37.5%); 0% <COX-2 index ≤35% (n=3/14 patients, 21.4%);35% <COX-2 index ≤70%(n=2/16 patients, 12.5%); 70% <COX-2 index ≤100% (n=7/22 patients, 31.8%); (B) grouped with respect to COX-2 index ≤ median (n=7/30 patients, 23.3%); COX-2 index > median (n=8/30 patients, 26.7%).

Figure 3

Expression of COX-2 in pituitary adenomas (optical microscope, magnification 200×); (A) female, 66 yrs: gonadotropinoma, COX-2 index =0%; (B) female, 75 yrs: gonadotropinoma, COX-2 index =100%.

Figure 4

Expression of COX-2 in patients with pituitary adenoma grouped according to their final diagnosis. Median values of COX-2 index (IQR) are given: Acromegaly 58.0% (IQR=81.3),Cushing disease 55.5% (IQR=37.0), prolactinoma 32.0% (IQR=75.0), gonadotropinoma 70.0% (IQR=96.5), thyrotropinoma 5.0% (IQR=0.0), silent-ACTH 60.5.0% (IQR=55.0), NFA 70.0% (IQR=37.0).

Figure 5

Expression of COX-2 in patients in whom no signs of tumour invasiveness were observed in MRI and in patients in whom one or more of such signs were observed (n=60).