Details

Autor(en) / Beteiligte

• Kinoshita, Yoshiaki
• Hamasaki, Makoto
• Matsumoto, Shinji
• Yoshimura, Masayo
• Sato, Ayuko
• Tsujimura, Tohru
• Kamei, Toshiaki
• Kawahara, Kunimitsu
• Iwasaki, Akinori
• Nabeshima, Kazuki

Titel

Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma

Ist Teil von

• Cancer cytopathology, 2021-07, Vol.129 (7), p.526-536

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Background Malignant pleural mesothelioma (MPM) is characterized by mutations in several genes, including cyclin‐dependent kinase‐inhibitor 2A/p16 in the 9p21 locus, BRCA1‐associated protein 1 (BAP1), and neurofibromatosis type 2 (NF2) in the 22q12 locus. Recent studies indicate that fluorescence in situ hybridization (FISH) detects hemizygous loss of NF2 in tissue specimens of MPM. The authors investigated whether NF2 FISH, either alone or in combination with other diagnostic assays (9p21 FISH, methylthioadenosine phosphorylase [MTAP] immunohistochemistry [IHC], and BAP1 IHC), effectively distinguishes MPM cells from reactive mesothelial cells (RMCs) in cell blocks prepared from pleural effusions. Methods FISH assays were used to examine the deletion status of NF2 and 9p21, and IHC was used to determine the expression of MTAP and BAP1 in cell blocks from 54 cases with MPM and 18 cases with RMCs. Results Hemizygous NF2 loss (chromosome 22 monosomy or hemizygous deletion) showed 51.9% sensitivity (48.1% for chromosome 22 monosomy and 3.7% for hemizygous deletion) and 100% specificity in differentiating MPM cells from RMCs. Combinations of NF2 FISH, 9p21 FISH, and BAP1 IHC assays yielded greater sensitivity (98.1%) than any assay alone (9p21 FISH, 61.1%; MTAP IHC, 52.8%; or BAP1 IHC, 60.4%). The level of hemizygous NF2 loss in cell blocks positively correlated with that in corresponding tissues. Furthermore, to overcome cytologic specimen‐specific challenges, FISH combined with cytokeratin AE1/AE3 immunofluorescence was necessary in 25.9% of MPM cases for FISH assessment of predominantly scattered MPM cells. Conclusions NF2 FISH alone or in combination with other diagnostic assays effectively differentiates MPM cells from RMCs in cell blocks prepared from pleural effusions. Fluorescence in situ hybridization (FISH) detection of NF2 gene deletion (NF2 FISH) in cell blocks obtained from pleural effusions is effective for the diagnosis of malignant pleural mesothelioma. Hemizygous NF2 loss (chromosome 22 monosomy or hemizygous deletion) is detected in 51.9% of patients with mesothelioma, but not in those with reactive mesothelial hyperplasia; a combination of NF2 FISH, 9p21 FISH, and BAP1 immunohistochemical assays yields greater sensitivity (up to 98.1%) than that detected for any of these diagnostic assays alone.