Anaplastic astrocytoma and glioblastoma are malignant brain tumors with a poor prognosis. The aim of our study was the complex investigation of the factors, those influence their aggressive behavior and proliferation (Ki-67, EGFR, MMP-9, PR, р53, vascular network formation), and the evaluation of their prognostic impact. These data could be used for optimization of target therapy in different groups of patients with diffuse astrocytic tumors Grade III-IV. Our study included 30 patients who were put through brain surgery for the first time and were divided into two equal groups: 15 patients who experienced a recurrence within 1 year after the surgery (1st group) and 15 patients without recurrence within 1 year after the surgery (2nd group). Postoperative tumor materials were obtained in formalin-fixed, paraffin-embedded blocks. In addition, we investigated the case histories of these patients. The expression of Ki-67, EGFR, MMP-9, PR, р53, VEGF, and CD34 was evaluated with immunohistochemical testing. Chi-squared test, Mann-Whitney U and Kruskal-Wallis H tests were performed for comparison of quantitative parameters between groups. Spearman’s rank correlation coefficient was used for the measure of rank correlation between quantitative variables. Results of our study showed, that there was a tendency (Uemp=75,00; р>0.05) to higher proliferative index in the 1st group (18,29±3,44) compared to the 2nd group (16,57±3,09). EGFR expression was significantly higher in the 1st group (Uemp=70.50; p<0.05). Moreover, the higher EGFR expression was associated with higher MMP-9 expression (Uemp=7.500; p<0.01) and lower p53 expression (rs= –0.62, p<0.001). The higher MMP-9 expression was also associated with higher vascularization index (MVD(VEGF)/MVD(CD34)) (rs=0.43; p<0.05). Our data confirm the close connections of different factors of tumor aggressiveness and the presence of molecule-biological discrepancy in homogenous histologically, but heterogenous prognostically groups of tumors. This evidence may be used in future for better-personalized therapy of patients with diffuse astrocytic tumors Grade III-IV.

The aim: to find the optimal combination of immunohistochemical markers for differential diagnosis and prognosis of small cell lung cancer in small biopsy samples. Materials and methods. The tumor specimens were divided into 3 groups: 1) 25 biopsy samples of small cell lung cancer before treatment; 2) 25 samples of small cell lung cancer procured from autopsies of patients, who underwent chemotherapy; 3) 15 biopsy samples of other lung tumors histologically similar to SCLC. All tumor samples were formalin fixed and paraffin embedded (FFPE). Immunohistochemical study performed with 5 primary antibodies: CD56, p16ink4A, TTF-1, CD117, Ki-67. Results. TTF-1 was positive in all small cell lung cancer, lung adenocarcinomas and atypical carcinoids. Expression of CD56 was positive in 100 % of tumors from 1st group and 92 % of these tumors had more than 25 % of positive tumor cells. Expression of p16ink4A was significantly higher in 1st group than in the 3rd one (р<0,001). The stepwise logistic regression was used for finding the best markers for differential diagnosis of small cell lung cancer in small biopsy samples. The next combination of markers was chosen: TTF-1/CD56 (score 2–4)/p16 ink4A/CD117 (sensitivity – 80 %; specificity – 86.67 %; р<0,001) where “score 2–4” means expression of CD56 more than in 25 % tumor cells. Expression of Ki-67 was higher in the 2nd group compared with the 1st one (р<0,001). Conclusion. Evaluation of p16 expression can be used as additional marker for differential diagnosis of small cell lung cancer. The following combination of markers: TTF-1/CD56 (score2-4)/p16 ink4A/CD117 could be useful in diagnosis of small cell lung cancer in small biopsy samples and in the choice of targeted chemotherapy. The further study in paired tumor samples of small cell lung cancer before and after chemotherapy is required to prove the significance of changes in expression of Ki-67, CD56, CD117 and p16ink4A

Харьковская медицинская академия последипломного образования Цель исследования: изучение случаев рецидивирования диффузных астроцитарных опухолей ІІІ-IV степени злокачественности с формированием рекомендаций для их последующей терапии. Материалы и методы. всего было изучено 25 случаев рецидивов, из них 15 случаев ранних рецидивов и 10 случаев поздних. Для оценки патоморфоза дополнительно были изучены первичные опухоли у пациентов из группы ранних рецидивов. Ретроспективно были проанализированы медицинские карты стационарных больных, проведено гистологическое исследование опухолей, иммуногистохимическое исследование с 12 маркерами: GFAP,

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Aim: to clarify the prognostic value of cytoplasmic p16ink4A, VEGF, MMP-9 and Ki-67 expressions in gastrointestinal stromal tumors (GISTs) and connection of different levels of these markers expression with aggressive transformation of GISTs. Materials and methods. Our study included 36 samples of primary tumors and 10 relapses of GIST and metastases in liver after primary combined treatment (surgery and chemotherapy with imatinib). The immunohistochemical study was performed with 4 primary antibodies: Ki-67, p16ink4A, VEGF and MMP-9. We used formalin fixed and paraffin embedded (FFPE) tissue samples for immunohistochemical study. Results. In our study we showed significant connection between levels of cytoplasmic expression of p16ink4A in primary GISTs and such markers of tumor aggressive behaviour as Ki-67, MMP-9 and VEGF (Fisher’s exact P-value = 0.000753; 0.000101 and 0.000048 respectively). Between cytoplasmic expression of p16ink4A and VEGF and also between p16ink4A and MMP-9 strong direct correlation was found (γ = 0.829, P < 0.05 and rs = 0.961, P < 0.05 respectively). The correlation between expression of Ki-67 and p16ink4A was also direct and strong (rs = 0.754, P < 0.05), but with some exclusions, that’s why this correlation needs further investigation in larger groups with preciser molecular analysis. Analysis of metastatic GISTs samples showed prominent levels of MMP-9 and VEGF expression. Conclusions. Our study has shown very important role of cytoplasmic expression of p16ink4A in GIST as one of the markers of aggressive behavior, which can be used in complex with other markers for more accurate prognosis of GISTs progression. Prominent levels of MMP-9 and VEGF expression in metastatic GISTs can be a marker of resistance to imatinib. So probably evaluation of MMP-9 and VEGF expression can be used as a tool for correct choice of chemotherapy for patients with GISTs.