Importance of Expression of DNA Repair Proteins in Non-Small-Cell Lung Cancer

Česká verzia

Authors: S. Rybárová ¹; J. Muri ²; I. Hodorová ¹; J. Vecanová ¹; M. Benický ³; D. Piovarči ²; P. Janík ²; J. Mihalik ¹; L. Mirossay ⁴
Authors place of work: Ústav anatómie, LF UPJŠ, Košice, Slovenská republika ¹; Národný ústav tuberkulózy, pľúcnych chorôb a hrudníkovej chirurgie, Vyšné Hágy, Slovenská Republika ²; Oddelenie patológie, UN L. Pasteura, Košice, Slovenská republika ³; Ústav farmakológie, LF UPJŠ, Košice, Slovenská republika ⁴
Published in the journal: Klin Onkol 2012; 25(5): 370-374
Category: Original Articles

Summary

Background:
Proteins XRCC1 and ERCC1 are involved in DNA repair. XRCC1 plays a role in DNA base excision repair and ERCC1 in nucleotide excision repair pathway. Higher expression profile of both proteins in cancer cells may contribute to development of drug resistance. ERCC1 is involved in removal of platinum adducts and might be a potential predictive and prognostic marker in NSCLC (non-small-cell lung cancer) treated with a cisplatin-based regimen. The purpose of study was determination of XRCC1 and ERCC1 levels and their correlation with basic clinicopathological parameters in NSCLC.

Patients and Methods:
In this study, 107 tumor samples diagnosed as NSCLC were immunohistochemically examined for expression of XRCC1 and ERCC1 proteins. Our results were compared to basic clinicopathological parameters: type of tumor, tumor grade and stage of disease. For statistical analysis, the chi-square test was used.

Results:
In squamous cell carcinoma and large cell carcinoma samples, the XRCC1 protein level was twofold higher (60% of positive samples) than in adenocarcinoma samples (35.5% of positive samples). We have found statistical correlation between XRCC1 protein expression and type of tumor (p = 0.0306). On the other hand, the statistical importance between the protein level versus grade and stage was not found. In the case of the ERCC1 protein, we observed the highest protein level in adenocarcinoma (64.5%) and squamous cell carcinoma (62.5%) samples. Next, we determined a significant difference in content of XRCC1 versus ERCC1 (35.5% vs 64.5%) in adenocarcinoma samples. Statistical chi-square test did not reveal any correlation between ERCC1 status and clinicopathological parameters.

Conclusion:
According to our results, XRCC1 represents an important mechanism of DNA repair in squamous cell and large cell carcinomas. Besides that, expression of XRCC1 was in correlation with type of tumor. In patients with adenocarcinoma and squamous cell carcinoma, we could assume increased resistance to platinum-based therapy because of high expectation of ERCC1 protein expression. However, its levels did not correlate with monitored clinicopathological parameters. The ERCC1 protein will be possibly an independent prognostic factor in NSCLC. To prove a true survival benefit of patients with expression of ERCC1, prospective validation of ERCC1 before clinical implication is needed in the future.

Key words:
DNA repair proteins – non-small-cell lung carcinoma – immunohistochemistry

Submitted:
29. 5. 2012

Accepted:
14. 7. 2012

Zdroje

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