Clinical and Prognostic Implications of 1p/19q, Promoter, and Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas.

BACKGROUND AND OBJECTIVE

Genetic alterations, including , and promoter mutations (-mu, -mu, -mu, respectively), 1p/19q co-deletion (1p/19q-codel), and promoter methylation (-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood.

METHODS

We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II-IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry.

RESULTS

In the 103 cases, -M was the most common alteration (70.9%), followed by mu (58.3%), mu (46.6%), 1p/19q-codel (34.0%), and -mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (-mu/-mu/-M/1p/19q-codel). The percentage of -mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of -mu and 1p/19q-codel cases decreased with Ki-67 expression. -mu, -M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while -mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, -mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis.

CONCLUSION

mu only and quadruple-positivity were associated with good OS in glioma patients, while -mu only, -mu/-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.