The prognostic significance of p16 expression pattern in diffuse gliomas

Park, Jin Woo; Kang, Jeongwan; Lim, Ka Young; Kim, Hyunhee; Kim, Seong Ik; Won, Jae Kyung; Park, Shin Young

doi:10.4132/jptm.2020.10.22

Cited by 20 publications

(14 citation statements)

References 35 publications

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“…Several studies have shown that CDKN2A is linked to poor prognosis of gliomas [31], head and neck cancers [32], and pancreatic ductal carcinomas [33]. Similarly, another report has discussed the correlation between CDKN2A and immune infiltration of HCC [34].…”

Section: Discussionmentioning

confidence: 97%

“…CDKN2A, which encodes a cell cycle-related CDK, P16, contributes to a series of cellular functions, including cell proliferation, apoptosis, angiogenesis and chemotherapy resistance of cancer [ 30 ]. Several studies have shown that CDKN2A is linked to poor prognosis of gliomas [ 31 ], head and neck cancers [ 32 ], and pancreatic ductal carcinomas [ 33 ]. Similarly, another report has discussed the correlation between CDKN2A and immune infiltration of HCC [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

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A Novel Cuproptosis-Related Signature Identified DLAT as a Prognostic Biomarker for Hepatocellular Carcinoma Patients

Bai¹,

Liu

et al. 2022

World J Oncol

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Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancers, with more than a million cases per year by 2025. Cuproptosis is a novel form of programmed cell death, and is caused by mitochondrial lipoylation and destabilization of iron-sulfur proteins triggered by copper, which was considered as a key player in various biological processes. However, the roles of cuproptosisrelated genes (CRGs) in HCC remain largely unknown. Methods:In the present study, we constructed and validated a four CRGs signature for predicting the overall survival (OS) of HCC patients in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Results:Patients with high CRGs risk score showed shorter OS than those with low CRGs risk score. Functional analysis suggested that the CRGs-based prognostic signature was associated with metabolism remodeling which facilitated liver cancer progression. In addition, reduced infiltration of CD8 + T cells and increased macrophages were found in HCCs from patients with high CRGs risk score. As one of the four CRGs, higher expression of dihydrolipoamide Sacetyltransferase (DLAT) was accompanied by higher expression of program death ligand 1 (PD-L1) in HCC. Further, we confirmed that DLAT was up-regulated and correlated with poor prognosis in a clinical HCC cohort. Conclusion:In conclusion, our study constructed a four CRGs signature prognostic model and identified DLAT as an independent prognostic factor for HCC, thus providing new clues for understanding the association between cuproptosis and HCC.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

A Novel Cuproptosis-Related Signature Identified DLAT as a Prognostic Biomarker for Hepatocellular Carcinoma Patients

Bai¹,

Liu

et al. 2022

World J Oncol

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“…A following study by Parkait et al did find significant association between p16 immunonegativity and CDKN2A deletion detected by FISH in glioblastoma [ 25 ]. Subsequently, Park et al found only moderate correlation between p16 expression (performed on tissue microarrays) and CDKN2A loss as determined by FISH, but demonstrated the strong prognostic value of p16 expression in IDH-mutant astrocytomas [ 26 ]. Most recently, Suman et al and Geyer et al showed evidence for the strong negative predictive value of p16 in detecting CDKN2A deletion, also using FISH for determining CDKN2A status [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

P16 immunohistochemistry is a sensitive and specific surrogate marker for CDKN2A homozygous deletion in gliomas

Vij

Cho

Yokoda

et al. 2023

acta neuropathol commun

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Molecular characterization of gliomas has uncovered genomic signatures with significant impact on tumor diagnosis and prognostication. CDKN2A is a tumor suppressor gene involved in cell cycle control. Homozygous deletion of the CDKN2A/B locus has been implicated in both gliomagenesis and tumor progression through dysregulated cell proliferation. In histologically lower grade gliomas, CDKN2A homozygous deletion is associated with more aggressive clinical course and is a molecular marker of grade 4 status in the 2021 WHO diagnostic system. Despite its prognostic utility, molecular analysis for CDKN2A deletion remains time consuming, expensive, and is not widely available. This study assessed whether semi-quantitative immunohistochemistry for expression of p16, the protein product of CDKN2A, can serve as a sensitive and a specific marker for CDKN2A homozygous deletion in gliomas. P16 expression was quantified by immunohistochemistry in 100 gliomas, representing both IDH-wildtype and IDH-mutant tumors of all grades, using two independent pathologists’ scores and QuPath digital pathology analysis. Molecular CDKN2A status was determined using next-generation DNA sequencing, with homozygous CDKN2A deletion detected in 48% of the tumor cohort. Classifying CDKN2A status based on p16 tumor cell expression (0–100%) demonstrated robust performance over a wide range of thresholds, with receiver operating characteristic curve area of 0.993 and 0.997 (blinded and unblinded pathologist p16 scores, respectively) and 0.969 (QuPath p16 score). Importantly, in tumors with pathologist-scored p16 equal to or less than 5%, the specificity for predicting CDKN2A homozygous deletion was 100%; and in tumors with p16 greater than 20%, specificity for excluding CDKN2A homozygous deletion was also 100%. Conversely, tumors with p16 scores of 6–20% represented gray zone with imperfect correlation to CDKN2A status. The findings indicate that p16 immunohistochemistry is a reliable surrogate marker of CDKN2A homozygous deletion in gliomas, with recommended p16 cutoff scores of ≤ 5% for confirming and > 20% for excluding biallelic CDKN2A loss.

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“…CDKN2A/B gene mutation can be tested through next-generation sequencing or the Sanger method if the tumor is IDH -mutant and 1p19q is not codeleted[ 19 ] (Figure 1 ). Loss of p16 expression (a marker of CDKNA/B) is associated with poor prognosis in IDH -mutant tumors and those with 1p/19q codeletion[ 20 ]. CDKN2A/B deletion is detected in both the wild-type and mutant IDH ; however, it has been related to a reduction in OS in wild-type tumors[ 21 - 23 ].…”

Section: Discussionmentioning

confidence: 99%

Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification

Kurdi¹,

Moshref²,

Katib³

et al. 2022

WJCO

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The classification of central nervous system (CNS) glioma went through a sequence of developments, between 2006 and 2021, started with only histological approach then has been aided with a major emphasis on molecular signatures in the 4th and 5th editions of the World Health Organization (WHO). The recent reformation in the 5th edition of the WHO classification has focused more on the molecularly defined entities with better characterized natural histories as well as new tumor types and subtypes in the adult and pediatric populations. These new subclassified entities have been incorporated in the 5 th edition after the continuous exploration of new genomic, epigenomic and transcriptomic discovery. Indeed, the current guidelines of 2021 WHO classification of CNS tumors and European Association of Neuro-Oncology (EANO) exploited the molecular signatures in the diagnostic approach of CNS gliomas. Our current review presents a practical diagnostic approach for diffuse CNS gliomas and circumscribed astrocytomas using histomolecular criteria adopted by the recent WHO classification. We also describe the treatment strategies for these tumors based on EANO guidelines.

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The prognostic significance of p16 expression pattern in diffuse gliomas

Cited by 20 publications

References 35 publications

A Novel Cuproptosis-Related Signature Identified DLAT as a Prognostic Biomarker for Hepatocellular Carcinoma Patients

A Novel Cuproptosis-Related Signature Identified DLAT as a Prognostic Biomarker for Hepatocellular Carcinoma Patients

P16 immunohistochemistry is a sensitive and specific surrogate marker for CDKN2A homozygous deletion in gliomas

Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification

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