COX-2 overexpression in peritoneal lesions is correlated with nonmenstrual chronic pelvic pain

OBJECTIVE: To investigate cyclooxygenase (COX-2) expression within different endometriotic lesions and to assess whether these expression patterns correlate with clinical characteristics. DESIGN: Retrospective cross-sectional study. SETTING: University Hospital. PATIENTS: Seventy patients with histologically confirmed exclusively peritoneal (n=20), ovarian (n=19) or deep-infiltrating (n=31) endometriosis and a detailed medical history. INTERVENTION: Immunohistochemical analysis for COX-2 was performed on 108 endometriotic lesions. MEASUREMENTS AND MAIN RESULTS: COX-2 intensity, percentage of stained glandular endometriotic cells, and correlation of COX-2 expression with clinicopathological parameters. Semiquantitative COX-2 expression did not differ between distinct morphological types of endometriosis and showed no association with the menstrual cycle. Patients with peritoneal-only 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, lower urinary tract symptoms or gastrointestinal symptoms was observed. CONCLUSION: Peritoneal endometriotic lesions with increased COX-2 expression have a special relevance for the development of chronic, nonmenstruation-associated, pelvic pain in endometriotic patients. These patients may benefit from therapy with COX-2 inhibitors.     

Cyclooxygenase-2 expression is higher in ovarian cancer tissue adjacent to endometriosis than in ovarian cancer without comorbid endometriosis

OBJECTIVES: The purpose of this study was to examine if COX-2, CK7 and CK20 are involved in the malignant transformation of endometriosis. METHODS: We compared COX-2, CK7 and CK20 expressions between isolated endometriosis lesions and endometriosis lesions adjacent to ovarian carcinoma and between isolated ovarian carcinoma and ovarian carcinoma with implants of endometriosis. Immunoreactivity was quantified using an immunohistochemical scoring system that corresponds to an image analysis-based system. RESULTS: There was no difference in COX-2, CK7 and CK20 expressions between the isolated endometriosis lesions and the endometriosis lesions adjacent to ovarian carcinoma. Similarly, CK7 and CK20 were equally expressed between the isolated ovarian carcinoma and the ovarian carcinoma with implants of endometriosis. The COX-2 over-expression rate was greater in ovarian carcinoma that was associated with endometriosis than in isolated ovarian carcinoma (27.8% versus 5.6%, P = 0.083). In endometrioid type ovarian carcinoma, the difference in COX-2 expression was statistically significant (50% versus 0%, P = 0.023). CONCLUSIONS: COX-2 over-expression may be a result of the malignant transformation of endometriosis to endometrioid type ovarian cancer or may represent an interaction between the two cellular components. With respect to cytokeratins, neither CK7 nor CK20 appear to be involved in the malignant transformation of endometriosis.     

Phospholipase A2 group IIA is elevated in endometriomas but not in peritoneal fluid and serum of ovarian endometriosis patients

Abstract

Our previous gene expression analysis identified phospholipase A2 group IIA (PLA2G2A) as a potential biomarker of ovarian endometriosis. The aim of this study was to evaluate PLA2G2A mRNA and protein levels in tissue samples (endometriomas and normal endometrium) and in serum and peritoneal fluid of ovarian endometriosis patients and control women. One-hundred and sixteen women were included in this study: the case group included 70 ovarian endometriosis patients, and the control group included 38 healthy women and 8 patients with benign ovarian cysts. We observed 41.6-fold greater PLA2G2A mRNA levels in endometrioma tissue, compared to normal endometrium tissue. Using Western blotting, PLA2G2A was detected in all samples of endometriomas, but not in normal endometrium, and immunohistochemistry showed PLA2G2A-specific staining in epithelial cells of endometrioma paraffin sections. However, there were no significant differences in PLA2G2A levels between cases and controls according to ELISA of peritoneal fluid (6.0?±?4.4?ng/ml, 6.6?±?4.3?ng/ml; p?=?0.5240) and serum (2.9?±?2.1?ng/ml, 3.1?±?2.2?ng/ml; p?=?0.7989). Our data indicate that PLA2G2A is implicated in the pathophysiology of ovarian endometriosis, but that it cannot be used as a diagnostic biomarker.     

C. albicans activates cyclooxygenase but not its product prostaglandin E2 in HPV 16-stabilized cells

Objective

The selective induction of cyclooxygenase-2 (COX-2) in human cells by Candida albicans was the first report of its role in infectious disease. This led us to question whether recurrent vulvovaginal candidosis in the cancer patient is involved in the formation of malignant tumors of the genital tract. Our speculation coincided with the patients’ assessments in our hospital, where few cancer patients had a prior history of Candida infection. We wanted to study the contribution of C. albicans to gynecological cancers.

Study design

In the present study, we used the developed vaginal epithelial cells system, having an insertion of HPV 16 viral sequence, as a model system (VK2/E6E7) to investigate the effect of Candida infection on prostaglandin E2 synthesis, which is known to be associated with cancers. We infected VK2/E6E7 cells with wild-type C. albicans and determined its effect on COX-2 and prostaglandin E₂ synthesis, and its alteration in dependence on p53, and we analyzed the ubiquitin-proteasome degradation pathways and the involvement of 14-3-3 protein, which is involved in the modulation of the cell cycle.

Results

Our work using the cellular model indicates that recurrent Candida infection of the genital tract in patients carrying HPV 16 viral infection blocks the proliferation of host cells, PGE2 synthase expression and thus PGE2 production.

Conclusion

We found that Candida infection contributes only to cell cycle arrest and does not by itself contribute actively to the development of cancer, although it is associated with patients diagnosed as having cancer of the genital tract induced by HPV 16 virus.     

The midluteal decline in serum estradiol levels is drastic but not deleterious for implantation after in vitro fertilization and embryo transfer in patients with normal or high responses

OBJECTIVE: To determine the impact of the peak E(2) level and its midluteal decline on IVF-ET outcome in a group of normal- and high-responding patients. DESIGN: Retrospective analysis of IVF-ET data. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENT(S): A total of 100 patients aged 98% E(2) decline; however, the difference did not reach statistical significance. CONCLUSION(S): Multifactorial analysis refutes the negative role of supraphysiologic levels of E(2) on the day of hCG administration or its dramatic decline at the midluteal phase on the success rate after embryo transfer. A possibly increased rate of early spontaneous abortion in the high-response group warrants further verification.