Prognostic value of complex assessment of Ki-67, tumor necrosis factor α, CD20 and CD31 expression in non-small cell lung cancer

Introduction. Non-small cell lung cancer is a common cancer with a poor prognosis. Modern researchers conduct many studies devoted to understanding the molecular mechanisms of its pathogenesis. Modern advances in immunotherapy have significantly improved the prognosis of patients with this pathology, but this is still not enough to control the course of the disease.

Objective – to the study of tumor (Ki-67, tumor necrosis factor α (TNF-α)) and stromal (TNF-α, CD20 and CD31) markers in non-small cell lung cancer and their prognostic significance.

Materials and methods. The study included tumor samples obtained from 100 patients with non-small cell lung cancer. The expression of Ki-67, TNF-α, CD20 and CD31 was assessed by immunohistochemistry. Survival analysis was carried out by constructing survival curves using the Kaplan–Meier method. To analyze the association of the expression of studied markers with clinical and morphological characteristics, the Mann–Whitney test was used. Differences were considered statistically significant at p <0.05.

Results. We analyzed the expression of Ki-67, TNF-α, CD20 and CD31 in non-small cell lung cancer tumors. Ki-67 expression was detected in tumor cells in 99 % of the samples studied and was not observed in stromal cells. In tumor and stromal cells, TNF-α expression was detected in 100 % of the samples. CD31 positive cells were also found in all samples studied, and CD20+B cells were present in 95 % of cases. TNF-α expression in tumor cells and tumor stroma is not associated with clinical and morphological characteristics. For the expression of CD20 in the tumor stroma, there was an association with tumor localization (p = 0.0435), with the stage of the disease (p = 0.0044), tumor size (p = 0.0017), and the presence of regional metastases (p = 0.0071). For Ki-67, there was a strong association with the histological type of tumor (p <0.0001), its localization (p = 0.0012) and the presence of regional metastases (p = 0.0020). The analysis of prognostic significance showed that TNF-α expression in tumor stroma cells is a favorable prognostic factor (hazard ratio 0.5547; p = 0.0139), while a high content of CD31+ cells is a factor of poor prognosis (hazard ratio 2.335; p = 0.0355). Next, we carried out a comprehensive analysis of the prognostic significance of the two identified markers simultaneously. It turned out that their combination of TNF-α/stroma (high expression)+CD31 (low expression) is a much more significant prognostic factor, in contrast to the individual analysis (hazard ratio 0.1966; p = 0.0048).

Conclusion. The study showed that a complex rather than an individual assessment of the predictive value of several markers simultaneously more effectively reflects their predictive ability.

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