Suppressed Expression of Caveolin-1 Characterizes Solitary Fibrous Tumors: Comparison with Other Mesenchymal Tumors and Malignant Mesotheliomas
Toru Motoi, Ikuma Kato, Yumiko Fukuda, Akihiko Yoshida, Shnichiro Horiguchi, Takahiro Goto, Tsunekazu Hishima. Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; National Cancer Center Hospital, Tokyo, Japan
Background: Solitary fibrous tumor (SFT) is a rare neoplasm, composed of bland, non-descript fibroblastic spindle cells immunoreactive to CD34. Caveolin-1 (Cav1), a scaffolding protein that regulates signal transduction and cellular metabolism, is known to play a key role in a subset of fibroblasts. For example, the cancer-associated fibroblast (CAF) is characterized by Cav1 deficiency and increased expression of pyruvate kinase isozyme M2 (PKM2). The expression status of Cav1 has not been studied in fibroblastic tumors. To clarify the nature of tumor cells in SFT and to identify diagnostic markers, we conducted immunohistochemical analysis of Cav1 and PKM2 in SFT and its mimics.
Design: 16 SFTs (5 pleural and 11 extrapleural) were immunostained with Cav1 and PKM2 antibodies. Non-SFTs that may mimic SFT were similarly examined. The latter included 16 malignant mesotheliomas, 20 fibroblastic tumors, 21 fibrohistiocytic tumors, 17 CD34-positive mesenchymal tumors, and 16 miscellaneous spindle cell tumors. Endothelium and CAFs (associated with breast cancer) were used as positive and negative controls, respectively. The staining results were scored as 0, 1, or 2.
Results: Cav1 expression was completely negative in 81% (13/16) of SFTs. In contrast, only 21% (19/90) of non-SFT tumors were negative; they included 90% (9/10) of synovial sarcoma (SS), 80% (4/5) of myxofibrosarcoma (MF), 12.5% (2/16) of malignant fibrous histiocytoma (MFH), 33.3% (2/6) of spindle cell lipoma (SL), and 40% (2/5) of dermatofibrosarcoma protuberans (DFSP). PKM2 was negative in 63% (10/16) of SFTs, whereas only 11.1% (10/90) of non-SFTs were negative for PKM2; the latter included 20% (2/10) of SS, 20% (1/5) of MF, 6.3% (1/16) of MFH, 50% (3/6) of SL, 40% (2/5) of DFSP, and 1.7% (1/6) of gastrointestinal stromal tumor. Notably, the Cav1−/PKM2− phenotype was observed in 63% (10/16) of SFTs, while only 4.4% (4/90) of non-SFTs exhibited this phenotype.
Conclusions: Suppressed expression of Cav1 characterizes fibroblastic tumor cells of SFT, and this finding may be useful for diagnosis. Furthermore, the Cav1−/PKM2− phenotype is highly characteristic of SFT in contrast to CAF, SS, and MF, which are mostly of the Cav1−/PKM2+ phenotype. Cav1 deficiency may be related to the distinct hemangiopericytomatous vascular proliferation that is commonly observed in SFT and SS.
Category: Bone & Soft Tissue
Monday, March 4, 2013 1:00 PM
Poster Session II # 18, Monday Afternoon