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Stem Cell Marker Nestin and c-Jun NH₂-Terminal Kinases in Tumor and Peritumor Areas of Glioblastoma Multiforme: Possible Prognostic Implications

Authors' Affiliations: ¹ Institute of Neurosurgery, ² Institute of Histology and Embryology, ³ Institute of Pathology, and ⁴ Unit of Epidemiology and Biostatistics-Institute of Hygiene, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy and ⁵ Departments of Neurosurgery and Experimental Pathology, New York Medical College, Valhalla, New York

Requests for reprints: Meena Jhanwar-Uniyal, Department of Neurosurgery, New York Medical College, Valhalla, NY 10595. Phone: 914-594-3186; E-mail: Meena_Jhanwar{at}nymc.edu or Gigliola Sica, Institute of Histology and Embryology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy. Phone: 39-06-3053261; Fax: 39-06-3053261; E-mail: ibiis{at}rm.unicatt.it.

Purpose: It has been hypothesized that brain tumors are derived from stem cell or transiently dividing precursor transformation. Furthermore, c-Jun NH₂-terminal kinases (JNKs) have been involved in gliomagenesis. This study analyzes stem cell marker nestin and JNK expression in glioblastoma multiforme (GBM) and peritumor tissue and assesses their possible prognostic implications.

Experimental Design: Nestin and both total JNK (tJNK) and phosphorylated JNK (pJNK) expression was investigated by immunohistochemistry in 20 GBMs. Samples were derived from tumors (first area), from tissues at a distance <1 cm (second area), and between 1 and 3.5 cm (third area) from the macroscopic tumor border. The relationships between patients' age, Karnofsky performance status, gender, protein expression, and survival were analyzed.

Results: Nestin cytoplasmic immunoreactivity was observed in the majority of cells in tumor but infrequently in peritumor areas. tJNK, observed in the nucleus and cytoplasm, was widely expressed in the three areas; pJNK, mostly located in the nuclei, was found in a variable percentage of cells in the tumor and peritumor tissue. Nestin and JNK expression in peritumor areas was independent of the presence of neoplastic cells. Univariate analysis indicated that survival was longer (19 versus 12 months; P = 0.01) for patients whose pJNK/nestin and (pJNK/tJNK)/nestin ratios in the second area were 2.619 and 0.026, respectively. The same variables showed an independent prognostic value in multivariate analysis.

Conclusions: Nestin and JNK expression indicates that peritumor tissue, independently of the presence of neoplastic cells, may present signs of transformation. Moreover, pJNK/nestin and (pJNK/tJNK)/nestin ratios in that tissue seem to have some prognostic implications in GBM patients.