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The prognostic significance of p16 expression pattern in diffuse gliomas
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Type
Academic journal
Author
Jin Woo Park (서울대학교병원) Jeongwan Kang (서울대학교병원) Ka Young Lim (서울대학교병원) Hyunhee Kim (서울대학교병원) Seong-Ik Kim (서울대학교) Jae Kyung Won (서울대학교병원) Park Chul-Kee (서울대학교) Park SungHye (서울대학교)
Journal
대한병리학회 Journal of Pathology and Translational Medicine Journal of Pathology and Translational Medicine 제55권 제2호 KCI Accredited Journals
Published
2021.1
Pages
102 - 111 (10page)

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The prognostic significance of p16 expression pattern in diffuse gliomas
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Background: 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. 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.
#Glioma #p16 #Immunohistochemistry #Prognosis #CDKN2A

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References (36)

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Foulkes WD / 1997 / The CDKN2A(p16)gene and human cancer / Mol Med 3:5~20 google schola Serrano M / 1997 / The tumor suppressor protein p16INK4a / Exp Cell Res 237:7~13 google schola Raschke S / 2005 / Homozygous deletions of CDKN2A caused by alternative mechanisms in various human cancer cell lines / Genes Chromosomes Cancer 42:58~67 google schola Appay R / 2019 / CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDHmutant gliomas / Neuro Oncol 21:1519~1528 google schola Reis GF / 2015 / CDKN2A loss is associated with shortened overall survival in lower-grade(World Health Organization Grades II-III)astrocytomas / J Neuropathol Exp Neurol 74:442~452 google schola

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