General Clinico-Pathological Characteristics in Glioblastomas in Correlation with p53 and Ki67

Abstract

Introduction: A glioblastoma is an intra-axial brain tumour of glial origin that belongs to the category of diffuse gliomas and is the most common malignant neoplasia of the central nervous system. The rate of survival at 5 years, from the moment of diagnosis, is not higher than 10%. Materials and methods: In this retrospective study, fifty-four patients diagnosed with glioblastoma, from the Pathology Department of the County Emergency Clinical Hospital of Târgu Mureș, between 2014 and 2017 were included. We studied the clinico-pathological data (age, gender, location, and laterality) and, respectively, the immunoexpression of p53, Ki67, ATRX, and IDH-1 proteins. Results: We observed a statistically significant association between the laterality of the tumour according to the age groups, with the localization on the right side being more frequent in the age group below 65 years of age, while the involvement of the left hemisphere was more prevalent in those over 65 years. Out of the total 54 cases, 87.04% were found to be primary glioblastomas; more than 70% of the cases were ATRX immunopositive; almost 80% of the glioblastomas studied had wild-type p53 profile; and 35% of the cases were found to have a Ki67 index greater than 20%. A statistically significant association between gender and ATRX mutation was found; female cases were ATRX immunopositive in 92% of the cases. Almost 70% of the cases were both IDH-1 and p53 wild-type, and we observed the presence of both mutations in only 3.7% of the cases. Approximately 83% of primary glioblastomas were ATRX positive, respectively, and all IDH-1 mutant cases were ATRX negative. Conclusions: Glioblastomas still represent a multidisciplinary challenge considering their reserved prognosis. In this study, we described the most common clinico-pathological characteristics and IHC marker expression profiles, highlighting a variety of percentage ranges in primary and secondary glioblastomas. Given the small number of studied cases, further prospective studies on larger cohorts are needed in the future to evaluate the role of these immunohistochemical markers as prognostic factors for survival or recurrence.

Evaluation of Microvascular Density in Glioblastomas in Relation to p53 and Ki67 Immunoexpression

“…IDH1 mutation expression was determined by quantifying positively stained cytoplasmic tumor cells, regardless of color intensity. Cases in which ≥10% of cells were stained were defined as positive ( IDH1 mutant), while cases where this value did not exceed 10% of tumor cells were considered negative ( IDH1 wild type) [ 55 ].…”

“…For the ATRX marker, ATRX gene mutations are followed by a loss of nuclear immunoexpression in over 50% of tumor cells ( ATRX loss– ATRX mutant type). If ATRX immunoexpression remains preserved in over 50% of tumor cells, the respective tumor is considered the ATRX wild type, with the endogenous positive control being endothelial cells [ 55 ].…”

“…The presence of p53 was determined using the percentage of immunopositive cells relative to 200 cells in 5 fields. We considered negative immunoexpression if immunostaining was present in <10% of tumor cells (wild type) and positive if >10% of examined tumor cells were immunopositive (mutant type) [ 55 ].…”