BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests.
Differentiation of malignant pleural mesothelioma (MPM) from benign mesothelial proliferation remains problematic. Loss of nuclear staining of BRCA1-associated protein 1 (BAP1; detected using immunohistochemistry (IHC)) and homozygous deletion (HD) of p16 (detected using fluorescence in situ hybridization (FISH)) are useful for differentiation of MPM from reactive mesothelial hyperplasia (RMH), but the correlation between BAP1 expression loss and p16 HD has not been fully described. We performed BAP1 IHC and p16-specific FISH for 40 MPM and 20 RMH cases, and measured proportions of cells showing BAP1 expression and p16 HD for each case. The diagnostic accuracy for MPM and the cut-off values of the two methods were assessed using receiver operating characteristic (ROC) analysis. BAP1 expression loss, p16 HD and coexistence of both were present in 27 (67.5 %), 27 (67.5 %) and 17 (42.5 %) MPM cases, respectively. Three MPM cases (7.5 %) and all 20 RMH cases had neither BAP1 loss nor p16 HD. There was no correlation between the results of the two methods. Their combination showed higher sensitivity (92.5 %, 37/40) and estimated probability than BAP1 IHC and p16-specific FISH used alone. BAP1 IHC and p16-specific FISH have independent diagnostic value, and have increased reliability when used in combination, for MPM diagnosis.
Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.|Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tomoyuki
T
Hida
Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.
Makoto
M
Hamasaki
Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.
Shinji
S
Matsumoto
Department of Pathology, Hyogo College of Medicine, Hyogo, Japan.
Ayuko
A
Sato
Department of Pathology, Hyogo College of Medicine, Hyogo, Japan.
Tohru
T
Tsujimura
Department of Pathology, Osaka Prefectural Medical Center for Respiratory and Allergic Disease, Osaka, Japan.
Kunimitsu
K
Kawahara
Department of Thoracic Surgery, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.
Akinori
A
Iwasaki
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tatsuro
T
Okamoto
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshinao
Y
Oda
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hiroshi
H
Honda
Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan. kaznabes@fukuoka-u.ac.jp.
Kazuki
K
Nabeshima
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis* / Q000096:biosynthesis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000175:diagnosis; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000175:diagnosis*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000096:biosynthesis; D043222:Ubiquitin Thiolesterase / Q000032:analysis* / Q000096:biosynthesis
C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
BAP1; Fluorescence in situ hybridization; Immunohistochemistry; Malignant pleural mesothelioma; ROC analysis; p16