The dissertation is devoted to the decision of an actual question of diagnostics and forecasting of regional metastasises of a laryngeal cancer (LC). To date, LC occupies an important place in the structure of tumors of the head and neck. Malignant tumors of the larynx are most represented by squamous cell carcinoma. The key factor is the presence of regional metastases, which significantly affects the survival of patients. According to studies, the presence of regional metastases of LC is observed in 20-65% of primary patients.
Purpose: Improving the effectiveness of diagnosis and treatment of patients with laryngeal cancer on the basis of clinical and morphological prediction of metastasis and determining the optimal treatment option.
A comprehensive immunocytochemical and immunohistochemical examination of patients was performed to detect and predict metastases of laryngeal malignancies. According to studies, regional metastases were detected in 65 patients (63.7%), who formed the main group. The other 37 patients (36.3%) with LC without metastasis were in the comparison group.
Immunocytochemical study with molecular markers of cytokeratin-19, matrix metalloproteinases 2 and 9 was performed in 74 patients, including 37 patients of the main group with regional metastases of laryngeal cancer and 37 patients of the comparison group. The prognostic value of matrix MMP-2 and MMP-9 relative to regional metastasis was determined by the presence of direct correlations between them (Rv = 0.450; p <0.001); (RV = 0.460, p <0.001).
Evaluation of the association between metastasis and the level of cytokeratin 19 expression in the lymph nodes (RV = 0.639, p <0.001) showed a significant relationship of moderate strength between them.
For immunohistochemical study, the following indicators were performed: sensitivity of Ki-67 - 100% (95% CI 91.0 - 100.0), AUC = 0.720, 95% CI (0.601 - 0.821) at p <0.001; cyclin D1> 50% sensitivity 82.1 (95% CI 66.5 - 92.4)% and specificity - 67.7 (95% CI 48.6 - 83.3)%; AUC = 0.780, 95% CI (0.665 - 0.870) at p <0.001; VEGF AUC = 0.701, 95% CI (0.575 - 0.801), sensitivity - 84.6 (95% CI 69.5 - 94.1)%; feature - 48.4 (95% CI 30.2 - 66.9)%, p = 0.002; CD34 AUC = 0.630, 95% CI (0.506 - 0.742) at p = 0.50, sensitivity - 74.4 (95% CI 57.9 - 86.9)%; feature - 51.6 (95% CI 33.1 - 69.8)%; Caspase-3 AUC = 0.719, 95% CI (0.599 - 0.820), sensitivity - 76.9 (95 CI 60.7 - 88.8)%; feature - 67.7 (95% CI 48.6 - 83.3)%, p <0.001; p21 WAF sensitivity 97.4 (95% CI 86.5 - 99.6)%, specificity - 45.2 (95% CI 27.3 - 64.0)% at p = 0.002, MMP-1 AUC = 0.677, 95% CI 0.555 - 0.784 (p 0.001) sensitivity 87.2 (95% CI 76.7 - 97.7)% and specificity 48.4 (95% CI 30.8 - 66.0)%; MMP-9 AUC = 0.618, 95% CI 0.504 - 0.732 (p = 0.047), TIMP-2 - AUC = 0.615, 95% CI 0.491 - 0.729 (p = 0.044).
The scientific novelty is that for the first time a method of immunocytochemical diagnosis of regional metastases of LC was developed with the analysis of expression of molecular markers MMP-2, MMP-9, and cytokeratin 19. The analysis of this study revealed a correlation with regional metastasis of LC, which allows the effectiveness of the TAPB method. For the first time, a study of the immunohistochemical profile of laryngeal cancer, which included molecular markers of invasion, apoptosis and cell proliferation. The obtained data on the expression of MMP-1, MMP-9 and TIMP-2, Ki-67, VEGF, CD-34, Cyclin D1, caspase 3 and p21WAF1 indicate the possibility of using this immunohistochemical profile as a prognostic. For the first time, the dependence of the volume of surgery on the lymph nodes of the neck in patients with LC was studied depending on the obtained data on morphological changes detected on the basis of expression of molecular markers of proliferation, apoptosis, neoangiogenesis and invasion.
The practical significance of the work is that the proposed method of immunocytochemical study significantly improves the diagnosis of regional metastases of laryngeal cancer. Also, this method of research allows to unify and facilitate the work of the diagnostic laboratory, in particular the laboratory doctor. The proposed immunohistochemical study of the complex of molecular markers allows to predict the detection of regional metastases of LC. The examination complex proposed as a result of the study can be used to improve the diagnosis of regional LC metastases.
Key words: laryngeal cancer, metastases, lymph nodes, immunohistochemical study, immunocytochemical study, lymph dissection, recurrence.
