Expression of Phospho-p38 MAPK and Phospho-p44/42 MAPK in Gliomas and Correlation with Patients' Outcome
V Zolota, Z Kefalopoulou, C Sirinian, A Argyriou, H Kalofonos. University of Patras Medical School, Patras, Greece
Background: Gliomas are devastating and aggressive human tumors and molecular pathogenesis has been under intense investigation as a part of the effort to develop more effective therapeutic strategies for these tumors. Mitogen-activated protein kinases (MAPK) are widely expressed serine-threonine kinases mediating important regulatory signals in the cell. Activation of MAPK cascades is believed to play a critical role in malignant transformation. This study investigates the role of expression of phospho-p38 and phospho-p44/42 (Erk1/2), two key components of the MAPK signalling pathway, as prognostic indicators in gliomas.
Design: The expression of p-p38 MAPK and p-p44/42 MAPK was evaluated in 62 gliomas using immunohistochemistry on formalin-fixed paraffin-embedded tissue specimens. Grade II astrocytomas were recorded as low-grade gliomas (n = 13, mean age = 47.6 ± 15.5 years, mean overall survival = 46.3 ± 12.1 months). Grade III anaplastic astrocytomas and grade IV glioblastomas were recorded as high-grade gliomas (n=49, mean age = 58.1 ± 12.3 years, mean overall survival = 18.9 ± 14.2 months). Results were expressed as %tumor cells displaying positive nuclear stain.
Results: The table lists the results. Expression of both markers was associated with more aggressive histological features (increased cellularity, nuclear atypia, mitotic activity, gemistocytes). Statistical analysis revealed a) a higher expression of both p-p38 and p-p44/42 in high-grade compared to low-grade gliomas (p<0.001) and b) a strong correlation between the two markers (r = 0.689, p < 0.001). Univariate analysis revealed that p-p44/42 expression was correlated with worse overall survival (p = 0.007). However, Cox regression failed to confirm that p-p44/42 constitutes an independent adverse prognostic factor.
|Total cases (n=62)||Low-grade (n=13)||High-grade (n=49)|
|p-p38||32.2 ± 20.9||9.6 ± 7.4a||38.2 ± 19.1a|
|p-p44/42||39.2 ± 22.7||19.4 ± 10.5b||44.5 ± 22.2b|
|a, b < 0.001|