PMID- 35738002 OWN - NLM STAT- MEDLINE DCOM- 20230301 LR - 20230301 IS - 1543-2165 (Electronic) IS - 0003-9985 (Linking) VI - 147 IP - 3 DP - 2023 Mar 1 TI - A Combination of MTAP and p16 Immunohistochemistry Can Substitute for CDKN2A Fluorescence In Situ Hybridization in Diagnosis and Prognosis of Pleural Mesotheliomas. PG - 313-322 LID - 10.5858/arpa.2021-0331-OA [doi] AB - 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 (/=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. FAU - Brcic, Luka AU - Brcic L AD - From the Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria (Brcic, Gallob). AD - The Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada (Churg). FAU - Le Stang, Nolwenn AU - Le Stang N AD - MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Centre Leon Berard, Lyon, France (Le Stang, Sequeiros, Karanian, Galateau-Salle). AD - The Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada (Churg). FAU - Gallob, Florian AU - Gallob F AD - From the Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria (Brcic, Gallob). FAU - Pissaloux, Daniel AU - Pissaloux D AD - The Unit of Molecular Pathology, INSERM 1052, CNRS 5286 of Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Universite Claude Bernard Lyon 1, Lyon, France (Pissaloux, Paindavoine, Tirode, Galateau-Salle). FAU - Sequeiros, Ruth AU - Sequeiros R AD - MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Centre Leon Berard, Lyon, France (Le Stang, Sequeiros, Karanian, Galateau-Salle). FAU - Paindavoine, Sandrine AU - Paindavoine S AD - The Unit of Molecular Pathology, INSERM 1052, CNRS 5286 of Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Universite Claude Bernard Lyon 1, Lyon, France (Pissaloux, Paindavoine, Tirode, Galateau-Salle). FAU - Pairon, Jean Claude AU - Pairon JC AD - Faculte de Medecine and CHI Creteil, Service de Pathologies Professionnelles et de l'Environnement, IST-PE, INSERM, UPEC, Creteil, France (Pairon). FAU - Karanian, Marie AU - Karanian M AD - MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Centre Leon Berard, Lyon, France (Le Stang, Sequeiros, Karanian, Galateau-Salle). FAU - Dacic, Sanja AU - Dacic S AD - The Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dacic). FAU - Girard, Nicolas AU - Girard N AD - EURACAN and Institute du Thorax Curie-Montsouris, Institut Curie, Paris, France (Girard). FAU - Churg, Andrew AU - Churg A AD - The Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada (Churg). FAU - Tirode, Franck AU - Tirode F AD - The Unit of Molecular Pathology, INSERM 1052, CNRS 5286 of Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Universite Claude Bernard Lyon 1, Lyon, France (Pissaloux, Paindavoine, Tirode, Galateau-Salle). FAU - Galateau-Salle, Francoise AU - Galateau-Salle F AD - MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Centre Leon Berard, Lyon, France (Le Stang, Sequeiros, Karanian, Galateau-Salle). AD - The Unit of Molecular Pathology, INSERM 1052, CNRS 5286 of Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Universite Claude Bernard Lyon 1, Lyon, France (Pissaloux, Paindavoine, Tirode, Galateau-Salle). AD - Faculte de Medecine and CHI Creteil, Service de Pathologies Professionnelles et de l'Environnement, IST-PE, INSERM, UPEC, Creteil, France (Pairon). LA - eng PT - Journal Article PL - United States TA - Arch Pathol Lab Med JT - Archives of pathology & laboratory medicine JID - 7607091 RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (Biomarkers, Tumor) RN - 0 (CDKN2A protein, human) SB - IM MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Homozygote MH - Sequence Deletion MH - *Mesothelioma, Malignant/diagnosis MH - *Mesothelioma/diagnosis/genetics/pathology MH - *Pleural Neoplasms/diagnosis/genetics/pathology MH - Prognosis MH - Cyclin-Dependent Kinase Inhibitor p16 MH - Biomarkers, Tumor/genetics/metabolism EDAT- 2022/06/24 06:00 MHDA- 2023/03/03 06:00 CRDT- 2022/06/23 17:42 PHST- 2022/02/02 00:00 [accepted] PHST- 2022/06/24 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2022/06/23 17:42 [entrez] AID - 483294 [pii] AID - 10.5858/arpa.2021-0331-OA [doi] PST - ppublish SO - Arch Pathol Lab Med. 2023 Mar 1;147(3):313-322. doi: 10.5858/arpa.2021-0331-OA.