Hsp27 (HSPB1): a possible surrogate molecular marker for loss of heterozigocity (LOH) of chromosome 1p in oligodendrogliomas. Correlation with histopathologic grade, Hsp70 (HSPA), PCNA, beta-catenin, p53 and MGMT

CASTRO G. N.; CAYADO-GUTIÉRREZ N.; MONCALERO V. M.; LIMA P.; LUCERO DE ANGELIS R.; CHÁVEZ V.; CUELLO CARRION F. D.; CIOCCA D. R.

Porto Alegre

Workshop; IX Cell Stress Society International Workshop on the Molecular Biology of Stress Responses; 2012

Cell Stress Society International

Introduction: Heat shock proteins (HSPs) are implicated in the genesis as well as in the progression of cancer. High HSP levels have been reported in central nervous system tumors, particularly in gliomas. Malignant gliomas comprise a wide variety of tumors from astrocytomas to oligodendrogliomas. Among the theories for cancer causation is emerging the concept of "obligate haploinsufficiency" in which partial loss of tumor suppressor genes is more tumorigenic than complete loss. In oligodendrogliomas 1p LOH is a predictor of good prognosis and treatment response. In contrast, in uveal melanomas LOH of chromosome 3 has been linked to poor prognosis and down-regulation of Hsp27. Objetives: To analyze the expression of HSPs to: a) characterize subtypes of gliomas and their histopathologic features, and b) correlate with other molecular markers including LOH of 1p. Methodology: Biopsies from patients with primary gliomas (n=63) were analyzed by IHC to examine Hsp27, Hsp70t (HSPA), Hsp70i (HSPA1A), beta-catenin, MGMT, PCNA and p53. FISH and CISH were used to study LOH of 1p. Methylation specific PCR was applied to study the status of the MGMT gene. Results: Elevated Hsp27 and Hsp70t expression levels were associated with high grade astrocytomas (p=0.0001 and p=0.01 respectively). In grade III oligodendrogliomas the Hsp27 levels were significantly higher (p=0.03). Low MGMT expression was associated with grade II astrocytomas. Elevated beta-catenin expression was associated with grade III/IV astrocytomas (p=0.003), p53 + tumors were more frequently found in grade III/IV astrocytomas (p= 0,001). LOH on 1p was associated with oligodendroglial tumours. In addition, a higher Hsp27 expression correlated with LOH of 1p (p=0.017). The determination of the MGMT methylation status was successful in only 6 samples. No significant correlations were found for the other markers. Conclusion: In oligodendroglial tumors Hsp27 could be used as a surrogate marker of LOH of 1p which could also help to predict the disease prognosis. We also showed significant interrelationships between the investigated molecular markers and clinicopathological characteristics in diffuse gliomas, suggesting that some of these markers could predict the disease outcome and the response to treatments.