Prognostic significance of cyclooxygenase 2 expression in 259 cases of non-small cell lung cancer.
ABSTRACT 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.
SourceAvailable from: Imtiyaz Rashid[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.Tumor Biology 07/2014; DOI 10.1007/s13277-014-2420-0. DOI:10.1007/s13277-014-2420-0 · 2.84 Impact Factor
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ABSTRACT: A new class of compounds targeting COX 2 has recently shown a promise for the chemoprevention of several solid tumors including lung cancer. Aim: To study the possible role of Cox-2 -8473 T/C NP and its expression in the pathogenesis of non small cell lung cancer. Methods. 190 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 analysed for COX 2 mRNA protein expression. Results. No significant association was observed in 3-UTR -8473T/C between lung cancer cases and control samples (P>0.5). COX-2 -8473TC and CC genotypes were associated more significantly in age group >50 years (P=0.02). Quantitative real Time expression analysis showed significant increase in the COX 2 mRNA in tumor tissues as compared to their adjacent normal tissues ((∆CT = 9.25 ± 4.67 vs5.63 ± 3.85, P=0.0001). Cox 2 mRNA also showed significant increase in the age group less than 50 years of age (P=0.004) and was further found more in stage I and II and in female patients. However COX 2 mRNA expression shown no association with the -8473T/C polymorphism. Conclusion. Our study showed increased COX 2 expresssion in more than 80% of tumor tissues of NSCLC and suggests that it could become an important therapeutic marker in NSCLC in future.Tumor Biology 08/2014; · 2.84 Impact Factor
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ABSTRACT: Cyclooxygenase-2 (COX-2) is an enzyme that has been extensively investigated as a prognostic marker in cancer. In non-small cell lung cancer (NSCLC) previous results regarding the prognostic impact of COX-2 expression are inconsistent. Therefore we evaluated the association between transcript levels and overall survival in nine publicly available gene expression data sets (total n = 1337) and determined in situ compartment-specific tumor and stromal cell protein expression in two independent cohorts (n = 616). Gene expression did not show any correlation with clinical parameters or with overall survival. Protein expression in tumor and stromal cells did not correlate with any clinical parameter or with overall survival in one of the analyzed cohorts, while a significant association of high stromal expression with longer survival was observed in both univariate and multivariate analysis in the other cohort. Stromal expression of COX-2 has not been separately evaluated in NSCLC previously and may be a subject of further investigation, whereas the presented findings from this comprehensive compartment specific evaluation clearly reject the hypothesis of COX-2 tumor cell expression having a prognostic value in NSCLC. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.Cancer Letters 10/2014; DOI:10.1016/j.canlet.2014.10.032 · 5.02 Impact Factor