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An effective cytotoxic immune response to neoplastic cells requires efficient presentation of antigenic peptides to T lymphocytes by HLA class I (HLA-I) molecules. The HLA-I-bound peptide repertoire depends on antigen-processing machinery molecules. Aminopeptidase residing in endoplasmic reticulum 1 (ERAP1) trims peptides to the optimal length for HLA-I binding. Single nucleotide polymorphisms (SNPs) in the ERAP1 gene result in changes in aminopeptidase activity and specificity. This may affect susceptibility to cancer. However, non-small cell lung carcinoma (NSCLC) has not been studied in this respect. We compared genotype and haplotype frequencies of four coding, nonsynonymous ERAP1 SNPs, rs26653G > C, rs26618T > C, rs30187C > T, and rs27044C > G, in NSCLC occurring in two genetically distant populations, Chinese and Poles. We found associations of all four SNPs with NSCLC in Chinese but not in Poles. The differences in ERAP1-NSCLC associations might be explained by highly significant differences in SNP genotype frequencies between Chinese and Poles (except for rs26618). In accordance with this, the most frequent ERAP1 haplotypes were distributed differently in cases versus controls in Chinese, but not in Poles. Our findings add to the differences between Orientals and Caucasians in genetics of disease susceptibility.

Unlabelled: Cancer cachexia syndrome is a common and important complication of cancer. It occurs in 30% to 80% cancer patients. It includes anorexia, loss weight, weakness and impaired immune function. The cause of the syndrome stays still unclear. Many endocrinological and metabolic abnormalities are observed, like hypermetabolism, glucose intolerance, increased proteolysis and lipolysis. Main role in the development of cancer cachexia is played by cytokines: TNF, interleukin 1 and 6, interferon alfa and gamma. The aim of the study was to collect information about cachexia in lung cancer patients, treated in Department of Pulmonology, Wrocław Medical University. We observed 76 patients with recent diagnosis of lung cancer (43 male, 33 female), 50 patients with non-small lung cancer and 26 with small lung cancer. Average age 61 +/- 9.76. We divided all patients in four groups, depending on percent of weight loss and compared these groups. We estimated extent of disease, anthropological and biochemical parameters. Among all patients we found cachexia in 23 (32%). There were only some differences between patients with and without cachexia. Bigger loss weight was observed in older men., Conclusions: Cachexia syndrome is not an important problem in lung cancer patients at the time of diagnosis.

The role of sex hormones in the pathogenesis of lung cancer is still unknown. There are conflicting results regarding immunohistochemical detection of the estrogen and progesterone receptors expression in non small cell lung cancer. To clarify these discrepancies 32 samples of lung carcinoma tissues obtained by lobectomy or pneumonectomy were studied. Two monoclonal antibodies (6F11 and ID5) for estrogen receptor detection and one (1A6) for progesterone receptor detection were used. Eighteen adenocarcinoma and 14 squamous cell carcinoma cases were investigated. There were 11 women and 7 men with adenocarcinoma and 4 women and 10 men with squamous cell carcinoma. Weak (+1) nuclear estrogen hormone receptor expression was detected in only one specimen of a woman with adenocarcinoma and in one specimen of a man with squamous cancer. None of the 32 blocks of paraffin embedded specimens expressed progesterone receptor. The positive estrogen and progesterone receptors expression in cancer tissue is an important argument against the pulmonary origin of the unknown primary tumor.

We investigated the association of p53 abnormalities (gene mutations by DNA sequencing and protein over-expression by immunostaining) with clinical data and prognosis in 74 patients with resected non-small cell lung cancer (NSCLC). DNA analysis of exons 5-8 of the p53 gene showed 34 mutations in 74 resected primary NSCLC (45.9%). Immunohistochemical study of the p53 protein revealed that 41 of 74 (55.4%) samples had positive staining. We found strong agreement between the results of the p53 protein expression test (p53-PE) and the p53 gene mutation test (p53-M) (Cohen's kappa = 0.65, 95% CI 0.48-0.82). Joint distribution of the results (analysed using the bivariate Dale model) was mainly influenced by, histological type of tumour. A positive result for the p53-PE test significantly increased (estimated odds ratio 84.5; 95% CI 8.89-803.03) the odds of observing a positive result in the p53-M test. In the univariate analysis (log rank test), positive results in the p53-M test and the p53-PE test were significantly associated with overall survival (P < 0.001 and P = 0.005, respectively). In the multivariate analysis (Cox's proportional hazard model), a positive result for the p53-M test significantly increased relative risk for overall survival (RR 9.56; 95% CI 2.62-34.87; P < 0.001). When the result of the p53-M test was accounted for, a positive result for the p53-PE test did not offer any additional prognostic information due to the strong dependence of results of the tests. However, when the result of the p53-M test was removed from the model, a positive result for the p53-PE test became a significant unfavourable prognostic factor (P = 0.009). We conclude that p53 gene mutation and protein expression analyses are in a strong agreement. Joint distribution of the results depends mainly on histological type of tumour. When considered separately, both tests are unfavourable prognostic factors in NSCLC. When the result of the p53-M test is taken into account, the p53-PE test does not offer any additional prognostic information.

Aberrations in the pathway composed of p16, cyclin D1/CDK4,6 and pRb (pRb pathway) which controls the transition from G1 to S phase occur frequently in various types of tumors. In the present study we analyzed immunohistochemically the expression of pRb, p16 and cyclin D1 in 1 12 primary non-small cell lung carcinomas (NSCLC). Loss of expression of pRb and p16 proteins was demonstrated in 15/112 cases and 64/112 cases, respectively. Inverse expression of pRb and p16 proteins was observed in 61 cases and was statistically correlated with advanced stage of the disease (p=0.03). Overexpression of cyclin D1 was detected in 34 cases and was more frequently observed in stage I than in stage III of the disease (p=0.02). Concomitant overexpression of cyclin D1 and lack of p16 was observed in 57% of cyclin D1-positive tumors. In summary, 82 of 112 analyzed cases showed an aberrant expression of at least one of the investigated proteins. These results indicate that although pRb protein expression is altered only in a small percentage of NSCLCs, the pRb pathway is disrupted very frequently in this type of tumor. There were no statistically significant correlations between changes in protein expression and histological type of tumor, gender, smoking habits and occupation of patients.