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Background: Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. The authors investigated the prognostic impact of expression of the cyclooxygenase (COX) isoforms, COX-1 and COX-2, on disease-free survival and progression-free survival in patients with primary breast carcinoma as well as the association between COX expression and other clinicopathologic parameters., Methods: In this study COX isoform expression was determined by immunohistochemistry in a cohort of 221 patients with primary breast carcinoma., Results: Expression of COX-2 was detected in 36% of breast carcinoma samples and was associated significantly with several clinicopathologic parameters, including positive lymph node status (P < 0.0005), larger tumor size (P < 0.0005), poor differentiation (P < 0.0005), vascular invasion (P = 0.03), and negative estrogen receptor status (P = 0.04). In contrast, COX-1 was expressed in 45% of tumors and was associated with smaller tumor size (P = 0.02) and with negative lymph node status (P = 0.01). In a univariate survival analysis, a significant association was observed between elevated COX-2 expression and decreases in disease-free survival (P = 0.0007) and overall survival (P = 0.02). In a multivariate analysis, expression of COX-2 was of borderline significance for disease-free survival (relative risk, 1.90; 95% confidence interval, 1.00-3.59), adjusting for tumor size, histologic grade, number of positive lymph nodes, and patient age. Elevated expression of COX-1 in tumor tissue had no statistically significant influence on patient prognosis., Conclusions: The current data suggest that increased expression of COX-2 may play a role in the progression of primary breast carcinoma. It remains to be investigated whether treatment with selective inhibitors of COX-2 may be an additional therapeutic option for patients with breast carcinoma., (Copyright 2003 American Cancer Society.)

The mitogen-activated protein kinase phosphatase-1, MKP-1 (CL100) is involved in inactivation of MAP-kinase pathways, regulation of stress-responses and suppression of apoptosis. We investigated expression of MKP-1 in 90 cases of primary ovarian tumors, 11 normal ovaries as well as 4 ovarian carcinoma cell lines. Immunohistochemical expression of MKP-1 protein was reduced in tissue from LMP tumors and invasive ovarian carcinomas compared to normal ovaries and cystadenomas. A moderate to strong expression of MKP-1 was detected in 57.6% of invasive ovarian carcinomas. In a descriptive univariate survival analysis, MKP-1 expression was a prognostic marker for shorter progression-free survival of patients with invasive ovarian carcinomas. Patients with carcinomas positive for MKP-1 had a median progression-free survival of only 18.3 months compared to 40.6 months for patients with carcinomas negative for MKP-1 (log-rank test, p = 0.019). Other prognostic parameters for progression-free survival were FIGO stage, grade and pT stage. In an exploratory multivariate analysis, we found that MKP-1 expression as well as FIGO stage and grade were independent prognostic factors for progression-free survival. In contrast to progression-free survival, we did not find any influence of MKP-1 expression on patient overall survival. We investigated expression and regulation of MKP-1 mRNA by Northern Blot in vitro using 4 ovarian carcinoma cell lines (SKOV-3, OVCAR-3, CAOV-3, OAW-42). MKP-1 mRNA was inducible by interleukin-1beta and tumor necrosis factor-alpha in SKOV-3 and OVCAR-3 cells, whereas CAOV-3 and OAW-42 expressed MKP-1 mRNA constitutively. In OVCAR-3 cells MKP-1 mRNA levels were strongly inducible upon treatment of cells with cisplatin. Our data indicate that MKP-1 is expressed in a subset of ovarian carcinomas and regulated by inflammatory mediators. Expression of MKP-1 may be associated with shorter progression-free survival times. Further studies are needed to determine whether MKP-1 expression is a clinically useful marker to estimate patient prognosis as well as the response to chemotherapy., (Copyright 2002 Wiley-Liss, Inc.)