Immunohistochemical and molecular detection of the expression of FGF23 in phosphaturic mesenchymal tumors including the non-phosphaturic variant.

Eisuke Shiba,Mitsuhiro Nakamoto,Kei Yabuki,Ryo Shibuya,Atsuji Matsuyama,Takahiko Kasai,Hiroshi Harada,Masanori Hisaoka

doi:10.1186/s13000-016-0477-3

Abstract

BackgroundPhosphaturic mesenchymal tumors (PMTs) are rare neoplasms that are often associated with tumor-induced osteomalacia (TIO) due to excessive serum levels of fibroblast growth factor 23 (FGF23). PMTs share overlapping histologic features with other types of tumors; thus, accurate pathological diagnosis may be challenging. We performed an immunohistochemical examination of FGF23 expression in PMTs and other types of tumors, together with pertinent molecular analyses.MethodsSeven PMTs (5 with TIO and 2 without TIO) and 46 other types of bone and soft tissue tumors were retrieved, and immunohistochemistry was performed using a commercially available anti-FGF23 antibody. In addition, FGF23 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR), using RNA extracted from formalin-fixed, paraffin-embedded tissues.ResultsImmunohistochemical analysis of FGF23 expression showed distinct, punctate staining in the cytoplasm in 5 PMTs with TIO, whereas FGF23 expression was negative in the 2 PMTs without TIO and the other 46 tumors. FGF23 mRNA expression was detected in all 4 PMTs examined, as well as in 1 chondromyxoid fibroma and 1 myxoid liposarcoma. The real-time RT-PCR data showed that the relative expression levels of the FGF23 mRNA tended to be higher in PMTs with TIO than in PMTs without TIO, or in the chondromyxoid fibroma specimen.ConclusionsOur data suggested that the feasibility of immunohistochemical detection of FGF23 may depend on the level of secreted FGF23 from tumor cells. Thus, immunohistochemistry for FGF23 is an useful diagnostic adjunct for PMT, although its utility appears to be limited in cases without TIO.

Highlights

Phosphaturic mesenchymal tumors (PMTs) are rare neoplasms that are often associated with tumor-induced osteomalacia (TIO) due to excessive serum levels of fibroblast growth factor 23 (FGF23)
In 2009, Bahrami et al [12] reported the diagnostic utility of detecting FGF23 transcripts in PMTs by the reverse transcription-polymerase chain reaction (RT-PCR) using formalin-fixed, paraffin-embedded (FFPE) tumor tissues
No FG322-3-positive cells were observed among the 2 PMTs without TIO (Fig. 2) or the 46 non-PMT tumors, non-specific nuclear and/or diffuse cytoplasmic staining was noted in 9 cases (Figs. 3 and 4)

Summary

Introduction

Phosphaturic mesenchymal tumors (PMTs) are rare neoplasms that are often associated with tumor-induced osteomalacia (TIO) due to excessive serum levels of fibroblast growth factor 23 (FGF23). Tumor-induced osteomalacia (TIO) was previously described as involving various types of bone and soft tissue tumors such as hemangiopericytoma (an obsolete term, which is referred to as solitary fibrous tumor), chondroblastoma, and osteosarcoma [1,2,3,4,5]. Diagnosis Phosphaturic mesenchymal tumor Chondromyxoid fibroma Chondroblastoma Chondrosarcoma Extraskeletal mesenchymal chondrosarcoma Osteosarcoma Synovial sarcoma Angiosarcoma Clear cell sarcoma Myxoid liposarcoma Solitary fibrous tumor Giant cell tumor of bone Giant cell tumor of tendon sheath Aneurysmal bone cyst. RT-PCR testing is highly sensitive, FGF23 mRNA is considered to be structurally normal and could be detected in non-PMT tumors, including aneurysmal bone cysts and chondromyxoid fibromas [12,13,14]. A more reliable diagnostic adjunct for routine pathology testing is required

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Results

Conclusion