Laga AC, Zander DS, Cagle PTPrognostic significance of cyclooxygenase 2 expression in 259 cases of non-small cell lung cancer. Arch Pathol Lab Med 129: 1113-1117
Previous studies report that increased expression of cyclooxygenase 2 (COX-2) correlates with poor clinical outcome in several malignancies, including non- small cell lung carcinoma (NSCLC). Cyclooxygenase 2 inhibitors have been reported to effectively inhibit carcinogenesis in colon cancer experimental models. We examined COX-2 expression in 259 cases of NSCLC to evaluate its prognostic significance. Sections of NSCLC from patients with a median 5-year follow-up were immunostained with COX-2 monoclonal antibody (1:150) using the Dako mouse EnVision;pl system. Extent of COX-2 expression in neoplastic cells was recorded as follows: 0, 0% to 10% of cells positive; 1, 11% to 33% positive; 2, 34% to 66% positive; and 3, more than 66% positive. Intensity was scored as either increased (+) or not increased (-), compared to internal control smooth muscle and endothelial cells. Kaplan-Meier analysis was used to assess the relationship between survival and COX-2 expression, using the log-rank test for statistical significance. No relationship was found between the extent and/or the intensity of COX-2 expression and patient survival when the entire cohort was considered. However, when separately analyzed according to disease stage and intensity of COX-2 expression, a significant relationship (P = .03) between increased COX-2 expression and shortened patient survival was found only in patients with stage I and II NSCLC. To our knowledge, this is the largest series of NSCLCs in which COX-2 has been investigated as a prognostic marker. The findings in this large series support previous studies of smaller cohorts that reported that increased COX-2 expression predicts poor outcome in patients with early-stage NSCLC.
[Show abstract] [Hide abstract] ABSTRACT: Abstract A new class of compounds targeting cyclooxygenase 2 (COX-2) together with other different clinically used therapeutic strategies has recently shown a promise for the chemoprevention of several solid tumors including lung cancer. The aim was to study the possible role of COX-2 -8473 T/C NP and its expression in the pathogenesis of non-small cell lung cancer. One hundred ninety non-small cell lung cancer (NSCLC) patients and 200 healthy age-, sex-, and smoking-matched controls were used for polymorphic analysis, and 48 histopathologically confirmed NSCLC patients were analyzed for COX-2 messenger RNA (mRNA) and protein expression. Our results showed that the frequencies of variant genotypes 8473 CT/CC were significantly less common in the cases (30.0 %) than in the controls (36 %), suggesting that the 8473C variant allele is related with lower susceptibility in NSCLC (OR=0.79, 95 % CI 0.54–1.4). However, the frequency of COX-2 -8473 TC and CC genotypes were significantly associated with age in NSCLC (P= 0.02). Quantitative real-time expression analysis showed a significant increase in the COX-2 mRNA in tumor tissues as compared to their adjacent normal tissues [delta cycle threshold (ΔCT) = 9.25 ± 4.67 vs 5.63 ± 3.85, P= 0.0001]. Multivariate logistic regression analyses revealed that the COX-2 expression was associated significantly with age (P=0.044). Also, an increasing trend was observed in stages I and II and in female patients compared to stages III and IV and male patients, respectively, but no statistical significance was observed. However, COX-2 mRNA expression shown no association with the -8473C variant allele. Our findings indicate that the COX-2 T8473C polymorphism may contribute to NSCLC cancer susceptibility in the Kashmiri population, while our expression analysis revealed a significant increase of COX-2 in tumor tissues as compared to their adjacent normal tissues, suggesting that it could become an important therapeutic marker in NSCLC in the future.0Comments 1Citation
- "Several studies have shown that the employment of selective COX-2 inhibitors can reduce lung tumor formation in carcinogen-treated animal models [36, 37] and can block the growth of human lung cancer cell both in vitro and in vivo . COX-2 expression status could be useful at early stages to distinguish those with worse prognosis and has the tendency to become an independent prognostic marker [10,394041424344454647. In our studied group of NSCLC, COX-2 mRNA was expressed at significantly higher levels (P=0.007) in tumor tissues of NSCLC patients as compared to their adjacent normal tissues (ΔCT for cancerous tissue as 9.25± 4.67 vs 5.63±3.85 in adjacent normal lung tissue). "
[Show abstract] [Hide abstract] ABSTRACT: Background Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas. Methods The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed. Results COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model. Conclusions COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis.0Comments 2Citations
- "Adenocarcinomas from all three locations may be of pancreatobiliary or intestinal type of differentiation . Overexpression of cyclooxygenase-2 (COX-2) has been described in several tumours, including colon, stomach, breast, lung, and urinary bladder45678910111213141516 . The COX-2 expression is a component of the cellular response to inflammation and is induced by several extracellular or intracellular stimuli, including proinflammatory cytokines , infectious agents, mitogens, hormones and growth factors [17,18] . "
- "Our result is concordant with previous literature demonstrating the over-expression of COX-2 (Murata H et al. 1999) (Fig. 1b, 5a). Our results demonstrate that the expression of COX-2 increase with advancement of tumor stage which is also concordant with previous report (Khunamornpong et al. 2009; Laga et al. 2005) (Fig. 1b, 5a). H. pylori infection is one of the important factors for the Gastric Carcinoma. "