Immunohistochemical detection of MTAP and BAP1 protein loss for mesothelioma diagnosis: Comparison with 9p21 FISH and BAP1 immunohistochemistry

被引：129

作者：

Hida, Tomoyuki ^{[1
,2
,3
]}

Hamasaki, Makoto ^{[1
]}

Matsumoto, Shinji ^{[1
]}

Sato, Ayuko ^{[4
]}

Tsujimura, Tohru ^{[4
]}

Kawahara, Kunimitsu ^{[5
]}

Iwasaki, Akinori ^{[6
]}

Okamoto, Tatsuro ^{[7
]}

Oda, Yoshinao ^{[2
]}

Honda, Hiroshi ^{[3
]}

Nabeshima, Kazuki ^{[1
]}

机构：

[1] Fukuoka Univ Hosp & Sch Med, Dept Pathol, Jonan Ku, 7-45-1 Nanakuma, Fukuoka 8140180, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[3] Kyushu Univ, Grad Sch Med Sci, Dept Clin Radiol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[4] Hyogo Coll Med, Dept Pathol, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638131, Japan

[5] Osaka Prefectural Med Ctr Resp & Allerg Dis, Dept Pathol, 3-7-1 Habikino, Habikino, Osaka 5838588, Japan

[6] Fukuoka Univ Hosp & Sch Med, Dept Thorac Surg, Jonan Ku, 7-45-1 Nanakuma, Fukuoka 8140180, Japan

[7] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

来源：

LUNG CANCER | 2017年 / 104卷

关键词：

Malignant pleural mesothelioma; MTAP; BAP1; Immunohistochemistry; 9p21; FISH; Diagnosis; MALIGNANT PLEURAL MESOTHELIOMA; METHYLTHIOADENOSINE PHOSPHORYLASE MTAP; PURINE METABOLIC ENZYME; HOMOZYGOUS DELETION; EXTRAPLEURAL PNEUMONECTOMY; HEMITHORACIC RADIATION; P16/CDKN2A EXPRESSION; CONCORDANT LOSS; HUMAN CANCERS; P16; FISH;

D O I：

10.1016/j.lungcan.2016.12.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objectives: Differentiating malignant pleural mesothelioma (MPM) from reactive mesothelial hyperplasia (RMH) is still challenging. Detection of homozygous deletion (HD) of 9p21 region including p16(INK4A) (p16) by fluorescence in situ hybridization (FISH) and immunohistochemical detection of loss of BRCA1 associated protein 1 (BAP1), are reliable markers for MPM diagnosis. However, not all laboratories are equipped to perform 9p21 FISH; immunohistochemistry (IHC) is a more common and feasible technique. Thus, we sought to develop a IHC-based method that could predict the deletion of p16 in MPM in concordance with 9p21 FISH. Materials and methods: We examined the expression of the 9p21.3-related proteins (p14, p15, p16, and methylthioadenosine phosphorylase (MTAP)) and BAP1 using IHC in 51 MPM and 25 RMH cases, and assessed their correlation with HD of p16 detected by FISH. The diagnostic usefulness of IHC of the 9p21.3-related proteins and BAP1 and their combinations was assessed using the cut-off values set by receiver operating characteristic (ROC) analysis. Results: Among the 9p21.3-related proteins, MTAP IHC findings showed best concordance with 9p21 FISH results (kappa coefficient of 0.69) and a specificity of 100%. We also examined the combinations of MTAP IHC with the other products. The loss of p16 and MTAP had better concordance (kappa coefficient of 0.71), although lower specificity (85%). For differentiating MPM from RMH, only MTAP showed 100% specificity among the 9p21.3-related proteins, as did BAP1 IHC and 9p21 FISH. Among BAP1 combinations, only that of BAP1 with MTAP showed 100% specificity. Its sensitivity was 76.5%, which was lower than BAP1 IHC and 9p21 FISH combination (84.3%), but higher than BAP1 IHC alone (60.8%) or 9p21 FISH alone (60.8%). Conclusions: A combination of MTAP or BAP1 loss detected by IHC can likely detect MPM with good sensitivity and 100% specificity, and serve as useful ancillary IHC for discriminating MPM from RMH. i3/4 (C) 2016 Elsevier Ireland Ltd. All rights reserved.

引用

页码：98 / 105

页数：8

共 44 条

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