Functional analysis of polymorphisms in the COX-2 gene and risk of lung cancer.

The enzyme cyclooxygenase 2 (COX-2) is known to be involved in tumorigenesis and metastasis in certain types of cancer. Nevertheless, the prognostic value of COX-2 overexpression and its polymorphisms in patients with non-small cell lung cancer (NSCLC) have yet to be fully elucidated. The aim of the present study was to investigate the association between the three most commonly studied COX-2 gene polymorphisms (-1195 G/A, -765 G/C and 8473 T/C) with COX-2 expression and lung cancer risk in a Brazilian cohort. In the present hospital based, case-control retrospective study, 104 patients with NSCLC and 202 cancer free control subjects were genotyped for -1195 G/A, -765 G/C and 8473 T/C polymorphisms using allelic discrimination with a reverse transcription quantitative polymerase chain reaction method. COX-2 mRNA expression was analyzed in surgically resected tumors from 34 patients with NSCLC. The results revealed that COX-2 expression levels were higher in tumor tissue compared with normal lung tissue. However, this overexpression of COX-2 was not associated with the patient outcome, and furthermore, none of the analyzed polymorphisms were associated with the risk of developing lung cancer, COX-2 overexpression, or the overall survival of the patients with NSCLC. Taken together, the findings described in the present study do not support a major role for COX-2 polymorphisms and COX-2 overexpression in lung carcinogenesis within the Brazilian population.

Amyloid-like fibrils are not detected in non-small cell lung cancer tissue samples.

Some proteins, canonically not associated with amyloid diseases, can aggregate into amyloid-like fibrils under special conditions. Our group hypothesized that stressful cancer microenvironment might induce the formation of insoluble deposits of p53 mutant protein. A cohort of 28 non-small cell lung cancer (NSCLC) patients was used to test the aforementioned hypothesis. Tumor specimens were assessed for TP53 mutations using DNA sequencing and for amyloid formation by Congo red staining. TP53 mutations were present in 57% of patients, whereas no amyloid deposits were detected in tissue sections under polarized light microscopy. Mutant p53 proteins are not associated with the appearance of amyloid-like fibrils in NSCLC samples, and DNA sequencing remains the standard method to detect such abnormality.