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

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.

PAI-1 is a critical regulator of FGF23 homeostasis

“…Phosphaturic mesenchymal tumors are rare, difficult to locate, and often linked to tumor-induced osteomalacia (TIO). Excessively high levels of FGF23, secreted by mesenchymal tumors, have been established as the causative factor for TIO, in which patients present with hypophosphatemia due to increased renal phosphate wasting, low vitamin D 3 levels, and reduced bone density ( 45 – 47 ). Although a number of different therapeutic approaches are currently being explored to treat this rare disorder, our observations indicate that pharmacological inhibition of PAI-1 may provide some therapeutic benefit in patients with TIO due to elevated FGF23.…”

Tumor-induced osteomalacia

“…The specificity of FGF-23 detection is more depended on the methods since non-PMT bone tumors could express FGF-23 mRNA as well [ 42 , 43 ]. Assays having been reported are reverse transcription-polymerase chain reaction (RT-PCR) to detect FGF-23 mRNA [ 5 , 43 ], immunohistochemical staining [ 44 ] and RNA scope Chromogenic in situ Hybridization (CISH) [ 36 ]. RT-PCR is a method with high sensitivity but low specificity and even a very low level of FGF-23 mRNA expression in non-PMT bone tumors could be detected, making it difficult to distinguish with chondromyxoid fibroma, myxoid liposarcoma and aneurysmal bone cyst [ 44 ].…”

“…Assays having been reported are reverse transcription-polymerase chain reaction (RT-PCR) to detect FGF-23 mRNA [ 5 , 43 ], immunohistochemical staining [ 44 ] and RNA scope Chromogenic in situ Hybridization (CISH) [ 36 ]. RT-PCR is a method with high sensitivity but low specificity and even a very low level of FGF-23 mRNA expression in non-PMT bone tumors could be detected, making it difficult to distinguish with chondromyxoid fibroma, myxoid liposarcoma and aneurysmal bone cyst [ 44 ]. Immunohistochemical staining, showed a sensitivity of more than 70% and 100% specificity for PMTs in studies of the Shiba et al.…”

“…Immunohistochemical staining, showed a sensitivity of more than 70% and 100% specificity for PMTs in studies of the Shiba et al. [ 44 ] and Yamada et al. [ 37 ], respectively.…”

CT and MR imaging features in phosphaturic mesenchymal tumor-mixed connective tissue: A case report

“…Phosphaturic mesenchymal tumor (PMT) is a polymorphous group of extremely rare mesenchymal tumors that often result in hypophosphatemic osteomalacia/rickets, caused by the overproduction of the phosphaturic hormone fibroblast growth factor 23 (FGF23) ( 1 – 7 ). PMTs occur more frequently in middle-aged adults, although the age of the patients can range from 3 to 73 years, and are originated predominantly from soft tissue or bone involving a single site ( 8 , 9 ).…”