Elevated cyclooxygenase-2 expression is associated with altered expression of p53 and SMAD4, amplification of HER-2/neu, and poor outcome in serous ovarian carcinoma - PubMed (original) (raw)

Elevated cyclooxygenase-2 expression is associated with altered expression of p53 and SMAD4, amplification of HER-2/neu, and poor outcome in serous ovarian carcinoma

Tiina-Liisa Erkinheimo et al. Clin Cancer Res. 2004.

Abstract

Purpose and experimental design: Cyclooxygenase-2 (COX-2) is frequently expressed in human adenocarcinomas and inhibition of COX-2 suppresses tumor formation in various animal models of carcinogenesis. We analyzed expression of COX-2 protein in human serous ovarian carcinomas by immunohistochemistry (n = 442) and by Western blotting (n = 12) and COX-2 mRNA by reverse transcriptase PCR (n = 12). COX-2 immunoreactivity was correlated to clinicopathological variables and to expression of p53 and SMAD4 as detected by immunohistochemistry and to amplification of HER-2/neu as detected by in situ hybridization.

Results: COX-2 mRNA expression was detected in 75% (9 of 12) and COX-2 protein in 42% (5 of 12) of the serous ovarian adenocarcinoma specimens as detected by reverse transcriptase-PCR and Western blot analysis, respectively. Moderate to strong (elevated) immunoreactivity for COX-2 was detected in 70% (310 of 442) of the tumors. Elevated COX-2 expression associated with reduced disease-specific survival (P = 0.0011), high histological grade (P < 0.0001), residual tumor size > 1 cm (P = 0.0111), and age > 57 years (P = 0.0099). Tumors with altered immunostaining pattern for p53 or SMAD4 expressed more frequently elevated levels of COX-2 when compared with the tumors with normal staining pattern of these tumor suppressor genes (P < 0.0001 and P = 0.0004, respectively). In addition, elevated COX-2 expression associated with amplification of HER-2/neu oncogene (P = 0.0479).

Conclusions: Our results suggest that elevated expression of COX-2 associates with reduced survival in serous ovarian carcinomas and that expression of COX-2 may be induced in these tumors by loss of tumor suppressor genes such as p53 and SMAD4 and by amplification of HER-2/neuoncogene.

PubMed Disclaimer

Cited by

Cyclooxygenase 2 promoted the tumorigenecity of pancreatic cancer cells.
Li W, Mao Z, Fan X, Cui L, Wang X. Li W, et al. Tumour Biol. 2014 Mar;35(3):2271-8. doi: 10.1007/s13277-013-1301-2. Epub 2013 Oct 22. Tumour Biol. 2014. PMID: 24146280
Effects of cyclooxygenase inhibitors on survival time in ovarian cancer xenograft-bearing mice.
Li W, Xu XL, Zhang J, Cai JH, Tang YX. Li W, et al. Oncol Lett. 2012 Dec;4(6):1269-1273. doi: 10.3892/ol.2012.929. Epub 2012 Sep 20. Oncol Lett. 2012. PMID: 23205124 Free PMC article.
Comparative analysis of clinicopathological correlations of cyclooxygenase-2 expression in resectable pancreatic cancer.
Hermanova M, Karasek P, Tomasek J, Lenz J, Jarkovsky J, Dite P. Hermanova M, et al. World J Gastroenterol. 2010 Apr 21;16(15):1879-84. doi: 10.3748/wjg.v16.i15.1879. World J Gastroenterol. 2010. PMID: 20397266 Free PMC article.
Progesterone Receptor Serves the Ovary as a Trigger of Ovulation and a Terminator of Inflammation.
Park CJ, Lin PC, Zhou S, Barakat R, Bashir ST, Choi JM, Cacioppo JA, Oakley OR, Duffy DM, Lydon JP, Ko CJ. Park CJ, et al. Cell Rep. 2020 Apr 14;31(2):107496. doi: 10.1016/j.celrep.2020.03.060. Cell Rep. 2020. PMID: 32294429 Free PMC article.
Cyclooxygenase-2 expression correlates with poor prognosis in pancreatic cancer.
Juuti A, Louhimo J, Nordling S, Ristimäki A, Haglund C. Juuti A, et al. J Clin Pathol. 2006 Apr;59(4):382-6. doi: 10.1136/jcp.2005.026831. Epub 2006 Feb 7. J Clin Pathol. 2006. PMID: 16467169 Free PMC article.

Elevated cyclooxygenase-2 expression is associated with altered expression of p53 and SMAD4, amplification of HER-2/neu, and poor outcome in serous ovarian carcinoma - PubMed (original) (raw)