Relationship between CDKN2A/B ve EGFR FİSH findings and morfological features to predict prognosis in Grade 2 and Grade 3 astrocytomas

Objective: Grade 2 and grade 3 astrocytomas are tumors seen in adults and young adults, especially in the frontal lobe of the central nervous system. Grade 2 and grade 3 astrocytomas are central nervous system tumors of adults and young adults which frequently occurs frontal lob localisation. The classical grading system based on histopathological features, which has been used in the classification of astrocytomas, caused inconsistency among pathologists and did not created significant differences in predicting the treatment and survival of patients. In recent years, classification systems based on both genetic characteristics, especially IDH mutation, as well as histopathological features of tumors have gained momentum and successful results have been obtained in predicting the survival of patients. CDKN2A/B gene is located on the short arm of the ninth chromosome that is involved in the synthesis of proteins that controls cell division by inhibiting cyclin-dependent kinases such as p16, p14 and p15. In recent years, multiple studies demonstrated that homologous deletions in CDKN2A/B gene is associated with poor clinical outcome. In addition, it has been determined that EGFR gene amplifications are associated with poor clinical outcomes in astrocytomas that do not show IDH mutations, altough data on this subject are limited in IDH mutant astrocytomas. Our aim is to classify grade 2 and grade 3 astrocytomas more objectively by determining the number of mitoses per 10 high power field (2,37 mm2) with the mentioned gene mutations and to predict survival of patients more accurately. Materials and methods: Thirty-nine cases with IDH mutation, loss of ATRX expression and/or P53 mutation, who were diagnosed with astrocytoma in Istanbul University, Istanbul Faculty of Medicine, Department of Pathology between 2016 and 2020 were included in the study. Survival datas and radiological findings of the patients obtained. The number of mitoses in 10 high power field (2,37mm2) were determined on HE stained slides, areas with high tumor density were marked. With the tissue microarray method, 10 blocks containing four tissues were created. CDKN2A/B, EGFR FISH analyses and ATRX immunohistochemistry analyses performed on these newly created blocks. CDKN2A/B deletion presence/rate, EGFR gene amplification and loss of ATRX nuclear expression immunohistochemically were determined.Results: The number of mitotic figures per 10 high power field (2,37mm2 ) in all cases ranged between 0 to 3. The number of mitotic figures had no significant effect on overall survival and disease free survival. Grade 2 and grade 3 tumors were found to be seen in similar age groups and had similar overall survival and disease free survival. Two cases had progression to grade 4 astrocytoma. CDKN2A/B FISH studies revealed high rate of homozygous deletion in two cases, but there was no evidence suggesting a poor clinical outcome. No amplifications was detected in EGFR FISH studies. Conclusion: It was observed that tumor grade and mitotic figures per 10 high power field had no significant effect on overall survival and dissease free survival. In two cases, a high rate of homozygous deletion in CDKN2A/B gene was detected, but follow-up periods were insufficient to comment on survival. No amplification detected in EGFR gene, and it was thought that there was no effective genetic mechanism in the pathogenesis of IDH mutant astrocytomas.