PMID- 36455270
OWN - NLM
STAT- MEDLINE
DCOM- 20221205
LR  - 20230123
IS  - 1092-0684 (Electronic)
IS  - 1092-0684 (Linking)
VI  - 53
IP  - 6
DP  - 2022 Dec
TI  - Role of CDKN2A deletion in grade 2/3 IDH-mutant astrocytomas: need for selective 
      approach in resource-constrained settings.
PG  - E17
LID - 10.3171/2022.9.FOCUS22427 [doi]
AB  - OBJECTIVE: The authors aimed to assess the frequency of homozygous CDKN2A 
      deletion in isocitrate dehydrogenase (IDH)-mutant diffuse astrocytomas (grade 
      2/3) and to narrow down the clinicopathological indications in which the CDKN2A 
      fluorescence in situ hybridization (FISH) assay is cost-effective in 
      resource-constrained settings. METHODS: IDH-mutant astrocytomas were analyzed for 
      ATRX, p53, MIB1-LI, and p16 expression using immunohistochemistry. The FISH assay 
      was used to evaluate CDKN2A deletion and 1p/19q codeletion. Survival outcomes 
      were assessed according to the different molecular markers. RESULTS: A total of 
      150 adult patients with IDH-mutant grade 2 (n = 95) and grade 3 (n = 55) 
      astrocytomas (145 primary and 5 recurrent) were analyzed. Using a cutoff value of 
      30% for defining significant homozygous CDKN2A deletion, none of the grade 2 and 
      10.9% (6/55) of grade 3 astrocytomas showed this deletion (4 primary and 2 
      recurrent grade 3 tumors) and were reclassified as grade 4. This mutation was 
      more frequent in recurrent (40%, 2/5) than primary (2.76%, 4/145) gliomas. Half 
      (3/6, 50%) of the CDKN2A-deleted cases demonstrated poor outcomes; 2 of these 
      cases experienced recurrence at 12 and 36 months after surgery, and 1 died at 5 
      months. The majority of CDKN2A-deleted cases showed marked cellularity (100%), 
      pleomorphism (100%), brisk mitosis (83.3%), and tumor giant cell formation 
      (83.4%). None of the cases with retained p16 expression harbored this deletion. 
      Both overall survival (p = 0.039) and progression-free survival (p = 0.0045) were 
      found to be worse in cases with p16 loss. Selectively performing CDKN2A FISH only 
      in high-risk cases with histomorphological features of anaplasia, p16 loss, or 
      recurrent tumors achieved a sensitivity and negative predictive value of 100%. 
      This approach would have resulted in saving 41.1% of the original expenditure 
      ($6900 US per 150 samples) and 27.6 person-minutes per sample without 
      compromising the identification of deleted cases. CONCLUSIONS: Homozygous CDKN2A 
      deletion is conspicuously absent in grade 2 and rare in primary grade 3 
      IDH-mutant astrocytomas. The authors propose that restricting use of the FISH 
      assay to cases showing histomorphological features of anaplasia, p16 loss, or 
      recurrent tumors will help this platform to be utilized in the most 
      cost-effective manner in resource-constrained settings.
FAU - Suman, Shalini
AU  - Suman S
AD  - 1Neuropathology Laboratory, and.
FAU - Sharma, Ravi
AU  - Sharma R
AD  - 2Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Katiyar, Varidh
AU  - Katiyar V
AD  - 2Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Mahajan, Swati
AU  - Mahajan S
AD  - 1Neuropathology Laboratory, and.
FAU - Suri, Ashish
AU  - Suri A
AD  - 2Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, 
      India.
FAU - Sharma, Mehar C
AU  - Sharma MC
AD  - 1Neuropathology Laboratory, and.
FAU - Sarkar, Chitra
AU  - Sarkar C
AD  - 1Neuropathology Laboratory, and.
FAU - Suri, Vaishali
AU  - Suri V
AD  - 1Neuropathology Laboratory, and.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurosurg Focus
JT  - Neurosurgical focus
JID - 100896471
RN  - 0 (CDKN2A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
SB  - IM
MH  - Humans
MH  - Anaplasia
MH  - In Situ Hybridization, Fluorescence
MH  - *Astrocytoma/genetics
MH  - *Glioma
MH  - Progression-Free Survival
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
OTO - NOTNLM
OT  - CDKN2A deletion
OT  - IDH-mutant astrocytoma
OT  - WHO 2021 classification
OT  - glioma
OT  - p16 loss
EDAT- 2022/12/02 06:00
MHDA- 2022/12/06 06:00
CRDT- 2022/12/01 17:22
PHST- 2022/07/31 00:00 [received]
PHST- 2022/09/20 00:00 [accepted]
PHST- 2022/12/01 17:22 [entrez]
PHST- 2022/12/02 06:00 [pubmed]
PHST- 2022/12/06 06:00 [medline]
AID - 10.3171/2022.9.FOCUS22427 [doi]
PST - ppublish
SO  - Neurosurg Focus. 2022 Dec;53(6):E17. doi: 10.3171/2022.9.FOCUS22427.