[1704] 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.

Expression levels of p-p38 and p-44/42 in low- and high-grade gliomas.

	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

Conclusions: Up-regulation of p-p38 and p-p44/42 in high-grade gliomas suggests that activation of MAPK signalling pathway may contribute to the acquisition of malignant properties and tumor progression in gliomas. The pathophysiological mechanism underlying the distinctive role of MAPK family in malignant transformation in gliomas as well as any putative therapeutic applications should be further investigated.
Category: Neuropathology

Tuesday, March 23, 2010 1:00 PM

Poster Session IV # 226, Tuesday Afternoon