Chromosome 1p and 19q status and p53 and p16 expression patterns as prognostic indicators of oligodendroglial tumors: a clinicopathological study using fluorescence in situ hybridization.
To verify the prognostic implications of the statuses of chromosome 1p and 19q and the expressions of p53, p16 and GFAP in oligodendrogliomas, we investigated these parameters and correlated the results with patient outcome. Twenty-seven cases of low-grade oligodendroglioma (LO) and 29 cases of anaplastic oligodendroglioma (AO) were analyzed by FISH for 1p and 19q status and by immunohistochemistry for p53, p16, and GFAP expression using a tissue microarray. Direct sequencing of the p53 gene was also performed. 1p deletion was observed in 39 of 56 patients (69.9%), and 19q deletion in 41 of 56 (73.2%). Combined loss of 1p and 19q was found in 38 of 56 (67.9%) and exhibited distinct concomitant deletion (P = 0.000). p53 overexpression was observed in 17 cases (30.3%), GFAP expression in 18 cases (32.1%), and p16 loss in 40 cases (74%) of oligodendrogliomas. The expressions of p53 and GFAP were more frequent in AO than in LO (P= 0.015 and 0.001). In contrast, p53 expression was more common in oligodendrogliomas with an intact 19q (P= 0.029), or an intact 1p (P= 0.071). Only five of 14 patients with p53 expression showed TP53 mutation, which was inversely correlated with 1p deletion (P= 0.036). Patients with combined loss of 1p and 19q exhibited better overall survival (P = 0.045). Patients with p53 expression without combined 1p and 19q loss showed poor overall survival (P < 0.000). However, TP53 mutation along with 1p and 19q status could not predict patient outcome. Patients with p16 loss without combined 1p and 9q loss showed poor overall survival (P = 0.011). Therefore, in oligodendrogliomas, the absence of the combined deletion of 1p and 19q and the aberrant expression of p53 or loss of p16 could be used as poor prognostic markers.
Jeon
Yoon Kyung
YK
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Park
Kyeongmee
K
Park
Chul Ki
CK
Paek
Sun Ha
SH
Jung
Hee Won
HW
Park
Sung-Hye
SH
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D019942:Genes, p16 / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009837:Oligodendroglioma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D005904:Glial Fibrillary Acidic Protein; D016159:Tumor Suppressor Protein p53