The prognostic significance of p16 expression pattern in diffuse gliomas

BACKGROUND: CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDK-N2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)–mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evalua...

Descripción completa

Detalles Bibliográficos
Autores principales: Park, Jin Woo, Kang, Jeongwan, Lim, Ka Young, Kim, Hyunhee, Kim, Seong-Ik, Won, Jae Kyung, Park, Chul-Kee, Park, Sung-Hye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Pathologists and the Korean Society for Cytopathology 2021
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987518/
https://www.ncbi.nlm.nih.gov/pubmed/33348944
http://dx.doi.org/10.4132/jptm.2020.10.22
Descripción
Sumario:BACKGROUND: CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDK-N2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)–mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evaluate whether p16 immunohistochemical staining could be used as a prognostic marker to replace CDKN2A genotyping in diffuse gliomas. METHODS: p16 immunohistochemistry was performed on tissue microarrays of 326 diffuse gliomas with diagnoses that reflected IDH-mutations and 1p/19q codeletion status. The results were divided into three groups (negative, focal expression, overexpression) according to the presence and degree of p16 expression. Survival analysis was performed to assess the prognostic value of p16 expression. RESULTS: A loss of p16 expression predicted a significantly worse outcome in all glioma patients (n = 326, p < .001), in the IDH-mutant glioma patients (n = 103, p = .010), and in the IDH-mutant astrocytoma patients (n = 73, p = .032). However, loss of p16 expression did not predict the outcome in the IDH-wildtype glioma patients (n = 223, p = .121) or in the oligodendroglial tumor patients with the IDH-mutation and 1p/19q codeletion (n = 30, p = .457). Multivariate analysis showed the association was still significant in the IDH-mutant glioma patients (p = .008; hazard ratio [HR], 2.637; 95% confidence interval [CI], 1.295 to 5.372) and in the IDH-mutant astrocytoma patients (p = .001; HR, 3.586; 95% CI, 1.649 to 7.801). Interestingly, patients who presented with tumors with p16 overexpression also had shorter survival times than did patients with tumors with p16 focal expression in the whole glioma (p < .001) and in IDH-mutant glioma groups. (p = .046). CONCLUSIONS: This study suggests that detection of p16 expression by immunohistochemistry can be used as a useful surrogate test to predict prognosis, especially in IDH-mutant astrocytoma patients.

Ejemplares similares