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SHR Neuro Cancer Cardio Lipid Metab Microb

Brcic, L; Le, Stang, N; Gallob, F; Pissaloux, D; Sequeiros, R; Paindavoine, S; Pairon, JC; Karanian, M; Dacic, S; Girard, N; Churg, A; Tirode, F; Galateau-Salle, F.
A Combination of MTAP and p16 Immunohistochemistry Can Substitute for CDKN2A Fluorescence In Situ Hybridization in Diagnosis and Prognosis of Pleural Mesotheliomas.
Arch Pathol Lab Med. 2023; 147(3):313-322 Doi: 10.5858/arpa.2021-0331-OA
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Leading authors Med Uni Graz: Brcic Luka
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Abstract:: CONTEXT.—: 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 (<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 (<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 (<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.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; Immunohistochemistry - administration & dosage; In Situ Hybridization, Fluorescence - administration & dosage; Homozygote - administration & dosage; Sequence Deletion - administration & dosage; Mesothelioma, Malignant - diagnosis; Mesothelioma - diagnosis, genetics, pathology; Pleural Neoplasms - diagnosis, genetics, pathology; Prognosis - administration & dosage; Cyclin-Dependent Kinase Inhibitor p16 - administration & dosage; Biomarkers, Tumor - genetics, metabolism