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Hyunhee Kim 1 Article
The prognostic significance of p16 expression pattern in diffuse gliomas
Jin Woo Park, Jeongwan Kang, Ka Young Lim, Hyunhee Kim, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Sung-Hye Park
J Pathol Transl Med. 2021;55(2):102-111.   Published online December 23, 2020
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AbstractAbstract PDF
CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDKN2A 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.
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.
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).
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.


Citations to this article as recorded by  
  • p16 Immunohistochemical Expression as a Surrogate Assessment of CDKN2A Alteration in Gliomas Leading to Prognostic Significances
    Lucas Geyer, Thibaut Wolf, Marie-Pierre Chenard, Helene Cebula, Roland Schott, Georges Noel, Eric Guerin, Erwan Pencreach, Damien Reita, Natacha Entz-Werlé, Benoît Lhermitte
    Cancers.2023; 15(5): 1512.     CrossRef
  • Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors
    Hyunhee Kim, Ka Young Lim, Jin Woo Park, Jeongwan Kang, Jae Kyung Won, Kwanghoon Lee, Yumi Shim, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi, Tae Min Kim, Hongseok Yun, Sung-Hye Park
    Laboratory Investigation.2022; 102(2): 160.     CrossRef
  • Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification
    Maher Kurdi, Rana H Moshref, Yousef Katib, Eyad Faizo, Ahmed A Najjar, Basem Bahakeem, Ahmed K Bamaga
    World Journal of Clinical Oncology.2022; 13(7): 567.     CrossRef
  • P16INK4A—More Than a Senescence Marker
    Hasan Safwan-Zaiter, Nicole Wagner, Kay-Dietrich Wagner
    Life.2022; 12(9): 1332.     CrossRef

JPTM : Journal of Pathology and Translational Medicine