In:
Archives of Pathology & Laboratory Medicine, Archives of Pathology and Laboratory Medicine, Vol. 147, No. 3 ( 2023-03-01), p. 313-322
Abstract:
Homozygous deletion (HD) of CDKN2A is one of the most frequent genetic abnormalities in pleural mesotheliomas. HD of CDKN2A by fluorescence in situ hybridization (FISH) is a reliable marker of malignancy in mesothelial proliferations; however, evaluation of CDKN2A deletion requires FISH. The 9p21 locus includes both CDKN2A and MTAP (methylthioadenosine phosphorylase); the latter is frequently codeleted with CDKN2A. Objective.— To examine the question of whether immunohistochemistry for MTAP and p16, the protein product of CDKN2A, can serve as a surrogate for CDKN2A HD by FISH. Design.— A random selection of 125 pleural mesothelioma cases was divided into 3 groups for evaluation of p16 and MTAP expression compared with FISH for CDKN2A deletion: 53 with HD, 39 with heterozygous deletion, and 33 without deletion. Results.— By itself, loss of p16 nuclear expression ( & lt;1% staining) showed a high sensitivity (96%) but low specificity (43%) for CDKN2A HD by FISH. MTAP cytoplasmic expression loss (≤30% staining) showed a 97% specificity and 69% sensitivity. The combination of p16 nuclear ( & lt;1% staining) and MTAP cytoplasmic (≤30% staining) loss demonstrated both high specificity (96%) and high sensitivity (86%). Patients with retained p16 expression (≥1%) had the best prognosis, whereas a p16 ( & lt;1%)/MTAP loss combination was associated with a dismal prognosis. Conclusions.— MTAP immunohistochemical staining is a valid surrogate marker for CDKN2A HD by FISH; however, to obtain the same accuracy as the FISH assay, a combination of nuclear p16 and cytoplasmic MTAP staining is recommended. These findings correlate with prognosis.
Type of Medium:
Online Resource
ISSN:
1543-2165
,
0003-9985
DOI:
10.5858/arpa.2021-0331-OA
Language:
English
Publisher:
Archives of Pathology and Laboratory Medicine
Publication Date:
2023
detail.hit.zdb_id:
2028916-9
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