Clinical and molecular validation of BAP1, MTAP, P53, and Merlin immunohistochemistry in diagnosis of pleural mesothelioma

被引：36

作者：

Chapel, David B. ^{[1
,2
]}

Hornick, Jason L. ^{[1
]}

Barlow, Julianne ^{[3
]}

Bueno, Raphael ^{[3
]}

Sholl, Lynette M. ^{[1
,4
]}

机构：

[1] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[2] Univ Michigan Michigan Med, Dept Pathol, Ann Arbor, MI 48109 USA

[3] Brigham & Womens Hosp, Dept Thorac Surg, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Ctr Adv Mol Diagnost, Boston, MA 02115 USA

来源：

MODERN PATHOLOGY | 2022年 / 35卷 / 10期

关键词：

IN-SITU HYBRIDIZATION; MALIGNANT MESOTHELIOMA; BRCA1-ASSOCIATED PROTEIN-1; TUMOR-SUPPRESSOR; HOMOZYGOUS DELETION; SEPARATE BENIGN; UNITED-STATES; GENE NF2; EXPRESSION; MUTATIONS;

D O I：

10.1038/s41379-022-01081-z

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

BAP1 and MTAP immunostains play an important role in diagnosis of mesothelioma, but additional markers are needed to increase sensitivity. We analyzed 84 pleural mesotheliomas (51 epithelioid, 27 biphasic, 6 sarcomatoid) by a hybrid-capture next-generation sequencing (NGS) panel including complete coverage of coding and splicing regions for BAP1, CDKN2A/MTAP, NF2, and TP53 and correlated molecular findings with diagnostic immunostains for BAP1, MTAP, Merlin, and p53, respectively. Fifty-seven reactive mesothelial proliferations served as benign comparators. Loss of BAP1, MTAP, and Merlin protein expression were, respectively, 54%, 46%, and 52% sensitive and 100% specific for mesothelioma. Two-marker immunopanels of BAP1 + MTAP, BAP1 + Merlin, and MTAP + Merlin were 79%, 85%, and 71% sensitive for mesothelioma, while a three-marker immunopanel of BAP1 + MTAP + Merlin was 90% sensitive. Diffuse (mutant-pattern) p53 immunostaining was seen in only 6 (7%) tumors but represented the only immunohistochemical abnormality in 2 cases. Null-pattern p53 was not specific for malignancy. An immunopanel of BAP1 + MTAP + Merlin + p53 was 93% sensitive for mesothelioma, and panel NGS detected a pathogenic alteration in BAP1, MTAP, NF2, and/or TP53 in 95%. Together, 83 (99%) of 84 tumors showed a diagnostic alteration by either immunohistochemistry or panel NGS. Adding Merlin to the standard BAP1 + MTAP immunopanel increases sensitivity for mesothelioma without sacrificing specificity. p53 immunohistochemistry and panel NGS with complete coverage of BAP1, CDKN2A/MTAP, TP53, and NF2 may be useful in diagnostically challenging cases.

引用

页码：1383 / 1397

页数：15

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