COX-2 Overexpression: A Potential Relevance for Chronic Pelvic Pain in Patients With Peritoneal Endometriosis

Abstract

To investigate cyclooxygenase-2 (Cox-2) expression in peritoneal, ovarian and deep infiltrating endometriotic lesions and to assess whether these expression patterns correlate with clinical characteristics Retrospective immunohistochemical study of formalin-fixed, paraffin-embedded tissue samples from patients with peritoneal, ovarian or deep infiltrating endometriosis Patients with histologically confirmed exclusively peritoneal (n=20), ovarian (n=19) or deep infiltrating (n=31) endometriosis, respectively, were included in the study. Endometriotic tissue was stained immunohistochemically with a monoclonal Cox-2 antibody (Cayman Chemical, Ann Arbor, Michigan, USA). A detailed medical history was obtained prospectively in all patients prior to surgery. The severity of symptoms (e.g. dysmenorrhoea, dyspareunia and chronic pelvic pain) was assessed by means of a subjective rating scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) based on the patients‘ self-assessment of pain. Staining intensity of endometrial glands was scored on a four-tiered scale as (0) no staining, (1) weak, (2) moderate or (3) strong immunoreaction. Additionally the proportion of stained glandular endometrial cells was scored as (1) low (>10-40%), (2) moderate (>40-60%), (3) high (>60-90%) and (4) all glands (>90-100%). The Cox-2 histological score was calculated as the sum of the maximum staining intensity and the percentage of stained glands. Staining results were correlated with morphological and clinical parameters. Statistical analysis was performed using the Mann Whitney U and χ2 test for non-parametric data. Patients with exclusively peritoneal endometriosis suffering from moderate or severe chronic pelvic pain showed significantly more frequent Cox-2 overexpression than asymptomatic patients or patients with minimal symptoms. In patients with exclusively ovarian or deep-infiltrating endometriosis no association between Cox-2 expression and clinical parameters such as chronic pelvic pain, dysmenorrhoea, dyspareunia, sterility or lower urinary tract symptoms or gastrointestinal symptoms was observed. Cox-2 expression did not differ between distinct morphological types of endometriosis. Cox-2 expression showed no association with the menstrual cycle. Separate analysis of patients with exclusively ovarian, deep-infiltrating or peritoneal endometriosis showed a statistically significant correlation between Cox-2 expression in peritoneal lesions and severity of chronic pelvic pain. Therefore, peritoneal endometriotic lesions with increased Cox-2 expression may have a special relevance for the development of chronic, non-menstruation-associated pelvic pain in endometriosis patients. These patients may benefit from therapy with Cox-2 inhibitors.