Peritoneal Malignant Mesothelioma (PMM), Papillary Serous Adenocarcinoma (PSA), and Reactive Mesothelial Hyperplasia (RMH) of the Peritoneum. An Immunohistochemical and Fluorescence In Situ Hybridization (FISH) Analysis
Toshiaki Kawai, Sadayuki Hiroi, Sho Ogata, Kuniaki Nakanishi, Kenzo Hiroshima, Toshihito Shinagawa, Seiichiro Shimizu. National Defense Medical College, Tokorozawa, Saitama, Japan; Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan; Kawasaki Municipal Ida Hospital, Kawasaki, Kanagawa, Japan; Showa General Hospital, Kodaira, Tokyo, Japan
Background: PMM is an uncommon tumor, accounting recently for only 7-9% of all mesotheliomas in Japan. Differential diagnosis between PMM and PSA may be difficult, and separating of RMH from PMM can be even more challenging. Studies describing the immunohistochemical and 9p21 FISH analyses of PMM are lacking. Differential diagnosis among PMM, PSA, and RMH of the peritoneum would be less difficult if it could be informed by mesothelial positive markers.
Design: To help differentiate PMM from PSA and RMH, we used (a) immunohistochemistry and (b) FISH to examine for: (a) mesothelial positive markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma markers (CEA, BerEP4, MOC31, ER, PgR), and malignant and benign related markers (EMA, desmin, GLUT-1, CD146, and IMP3) and (b) homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 20 PMMs (M:F=16:4; subtypes: 9 epithelioid, 6 biphasic, 5 deciduoid), 11 PSAs, and 23 RMHs.
Results: Fifteen of the mesotheliomas were classified as diffuse, while 5 were localized. Calretinin was at a high positive rate (90%) in PMM, but negative in PSA, with both sensitivity (90%) and specificity (100%) being very high. BerEP4 was at a high rate (100%) in PSA, but negative in PMM, with both sensitivity (100%) and specificity (100%) being very high. For the differentiation of PMM from RMH of the peritoneum, the sensitivity and specificity for EMA in mesothelioma were 65% and 100%, respectively. For GLUT-1, sensitivity was 50% and specificity 100%. For IMP3, sensitivity was 12% and specificity 95%. Homozygous deletion was considered to be present if both 9p21 signals were lost in at least 20% of nuclei and at least one signal for chromosome 9 copy number probe was shown in each nucleus. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/11 of PMM, but in none of RMH.
Conclusions: Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PSA of the peritoneum. EMA displayed high specificity, but a lower sensitivity than previously reported. Homozygous deletion of 9p21 (assessed by FISH) may be helpful for differentiating PMM from RMH.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 112, Wednesday Morning