Comparing loss of p16 and MTAP expression in detecting CDKN2A homozygous deletion in pleomorphic xanthoastrocytoma
Related Experiment Video
Updated: May 13, 2026
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
M Adelita Vizcaino1, Caterina Giannini1,2, Rachael A Vaubel1
1Department of Laboratory of Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
Abstract:
Pleomorphic xanthoastrocytomas (PXAs) harbor CDKN2A homozygous deletion in >90% of cases, resulting in loss of p16 expression by immunohistochemistry. Considering the proximity of MTAP to CDKN2A and their frequent concurrent deletions, loss of MTAP expression may be a surrogate for CDKN2A homozygous deletion. We evaluated p16 and MTAP expression in 38 patient PXAs (CNS WHO grade 2: n = 23, 60.5%; grade 3: n = 15, 39.5%) with available chromosomal microarray data to determine whether MTAP can be utilized independently or in combination with p16 to predict CDKN2A status. CDKN2A, CDKN2B, and MTAP homozygous deletion were present in 37 (97.4%), 36 (94.7%), and 25 (65.8%) cases, respectively. Expression of p16 was lost in 35 (92.1%) cases, equivocal in one (2.6%), and failed in 2 (5.3%), while MTAP expression was lost in 27 (71.1%) cases, retained in 10 (26.3%), and equivocal in one (2.6%). This yielded a sensitivity of 94.6% for p16 and 73.0% for MTAP in detecting CDKN2A homozygous deletion through immunohistochemistry. MTAP expression was lost in the 2 cases with failed p16 staining (combined sensitivity of 100%). Our findings demonstrate that combined p16 and MTAP immunostains correctly detect CDKN2A homozygous deletion in PXA, while MTAP expression alone shows reduced sensitivity.
Insights
Combined p16 and MTAP immunostains accurately detect CDKN2A homozygous deletion in pleomorphic xanthoastrocytomas (PXAs). MTAP expression alone is less sensitive for predicting this genetic alteration in PXA tumors.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Cancer Genetics
Background:
- Pleomorphic xanthoastrocytomas (PXAs) frequently exhibit CDKN2A homozygous deletion, leading to p16 loss.
- The proximity of Methylthioadenosine phosphorylase (MTAP) to CDKN2A suggests concurrent deletions, making MTAP a potential surrogate marker.
Purpose of the Study:
- To evaluate the utility of p16 and MTAP expression, assessed by immunohistochemistry, in predicting CDKN2A homozygous deletion in PXAs.
- To determine if MTAP can serve as an independent or combined biomarker with p16 for CDKN2A status in PXA.
Main Methods:
- Analysis of p16 and MTAP expression via immunohistochemistry in 38 patient-derived PXAs.
- Correlation of protein expression with chromosomal microarray data to confirm homozygous deletions.
- Calculation of sensitivity for p16 and MTAP in detecting CDKN2A homozygous deletion.
Main Results:
- CDKN2A homozygous deletion was identified in 97.4% of PXAs.
- Loss of p16 expression was observed in 92.1% of cases, showing 94.6% sensitivity for CDKN2A deletion.
- Loss of MTAP expression occurred in 71.1% of cases (73.0% sensitivity); combined p16/MTAP staining achieved 100% sensitivity.
Conclusions:
- Combined p16 and MTAP immunostaining is a reliable method for detecting CDKN2A homozygous deletion in PXAs.
- While MTAP expression loss is frequent, it demonstrates reduced sensitivity compared to p16 for predicting CDKN2A deletion individually.
