Significance Of FGF23 At Protein And RNA Levels In The Diagnosis Of Phosphatruic Mesenchymal Tumor

Background:Phosphaturic mesenchymal tumor?PMT?is a rare soft tissue tumor whose blood phosphorus decreases and urine phosphorus increases,and is the main tumor type causing tumor-induced osteomalacia.Although the symptoms can be relieved or even cured after the discovery and resection of the tumor,PMT is not only widely distributed in the body,but also occurs at hidden sites,and is often difficult to locate due to slow growth.For a long time,the patient only presented systemic bone and joint pain of unknown reasons,with decreased blood phosphorus and increased urine phosphorus.Symptomatic treatment was taken clinically,but the treatment effect was often poor due to the persistent focus.According to tumor cell excessive expression of somatostatin receptor?somatostatin receptor,SSTR?,the characteristics of some radioactive nuclide labeled half-life long somatostatin analogues is introduced into the body,combined with receptors on the surface of the tumor specificity,seeking to achieve?cancer?for tumor imaging and treatment,the purpose of the imaging agent 68 GA-DOTA-TATE has higher affinity with SSTR2A.The best treatment is still complete resection of the tumor under correct pathological diagnosis.However,due to the lack of characteristic histomorphological characteristics of PMT,pathologists lacking clinical data or experience in diagnosis of this tumor are very likely to be confused with other soft tissue tumors,resulting in misdiagnosis of some cases.Recent studies have shown that tumor cells produce too much fibroblast growth factor 23?FGF23?,which can reduce blood phosphorus levels by reducing phosphorus reuptake in the kidneys and absorb in the gut.Recent studies using second-generation sequencing technology have found that the fusion gene of FN1-FGFR1 exists in tumor induced osteomalacia?TIO?^[1],suggesting that the presence of FN1-FGFR1 fusion gene promotes the overexpression of FGF23^[2-4].Other studies have shown that the rearrangement of FGFR1 gene in TIO may also be related to the overexpression of FGF23.Therefore,detection of FGF23 and SSTR2A expression combined with pathomorphological changes is of more important significance for the diagnosis of phosphaturic mesenchymal tumor.However,so far,there is still a lack of studies on the expression of FGF23 in PMT using the method of immunohistochemistry and PCR comparison,and there is also a lack of experimental data on whether the two methods combined have higher sensitivity.In this paper,the significance of detecting the expression of FGF23protein and RNA in the diagnosis of phosphaturic mesenchymal tumor was discussed in combination with 4 typical PMT cases collected in clinical practice.Methods:A total of 4 cases with pathological diagnosis of PMT in the first affiliated hospital of China medical university from January 2012 to September 2018 were collected.Collect and sort out the medical records,including general state,clinical symptoms,signs,treatment and outcome,etc.B ultrasound,PET-CT or somatostatin receptor imaging were used to detect the tumor growth site and size.The original pathological sections were re-examined and made into 4um sections for FGF23 and SSTR2A immunohistochemical staining.RNA was extracted from paraffin specimens,and the tissue mRNA was extracted with a kit and then reversely transcribed.FGF23mRNA was quantitatively analyzed by RT-PCR according to the fragment sequence of FGF23 primer in the literature.Results:1.SSTR2A was positively expressed in 3/4 cases,FGF23 was positively expressed only in sample 2,and only a few cells were positively expressed in the peripheral tissues of the sections of other samples.2.RT-PCR showed that the expression of FGF23 mRNA in 4/4 samples was significantly higher than that of internal reference GAPDH gene.Conclusion:Protein expression of FGF23 and SSTR2A can be detected in the PMT through immunohistochemical staining,although SSTR2A positive rate is higher than the positive rate of FGF23,but cannot do one hundred percent,so the SSTR2A and FGF23 immunohistochemical staining negative cases could not rule out the diagnosis of PMT,namely SSTR2A and FGF23 immunohistochemical staining in diagnosis of PMT has only a supporting role.FGF23 mRNA in PMT detected by RT-PCR method has a high sensitivity,which is obviously better than the immunohistochemical method,and has guiding significance for the diagnosis of phosphate urinary mesenchymal tumor.