Expression Of Corticotropin Releasing Factor (CRF) Receptor 1 In Tumors Of The Nervous System

CRF is an important hypothalamic neuropeptide, which primarily through its receptor regulates the hypothalamus - pituitary - adrenal (HPA) axis function when the body be under stress, coordinats the endocrine system, the autonomic nervous system and immune system function under stress,and has a moderating effect on cardiovascular, gastrointestinal, reproductive, skin, etc. over-expression of CRF and its receptor has also been found in some types of human malignancies, and in some animal models the expression of CRF and its receptor has confirmed that it is related to tumor proliferation, metastasis, angiogenesis and immune evasion, etc.Objective:To investigate the expression of corticotropin releasing factor receptor 1 (CRFR1) in part of the human neurogliomas, pituitary tumors and human U87 glioma cells, and the interaction between the expression of CRFR1 in human glioma and the expression of glioma markers MGMT, GFAP, P53, and MMP-9.Methods:30 surgical biopsy specimens of some types of neurogliomas, 10 cases of pituitary adenoma biopsy specimens were randomly collected, and cultured human glioblastoma cell line U87, respectively, applied CRFR1 antibody to the tissue samples collected and cells cultured in Immuno- histochemical staining and then analyze the results. And further analyze the inter-relationship between the expression of CRFR1 in glioma and glioma markers MGMT, GFAP, P53, and MMP-9. The total RNA were extracted from cultured cells, and designed the primer of CRFR1 for the RT-PCR experiments, and analyze the expression of CRFR1.Results:Positive principal located in the cell membrane area and presented a clear yellow or brown in neurogliomas. CRFR1-positive samples can be seen in the tumor cells, many of which had larger size, round and large nuclei and a larger karyoplasmic ratio, and some stained slightly stronger presented brown, some stained weaker presented light yellow. In different cases, large differences in the percentage of positive cells about from 5% to 75%. The majority of mesenchymal tissue cells were negative, and in some cases can also be found that the expression of vascular endothelial cells were also positive. from 30 cases of neurogliomas, 14 were positive, including 7 positive astrocytoma cases, the expression of which were weakly positive to moderately positive, accounted on the total astrocytoma 43.5% (7 / 16), the pathologic level of gradeâ…¡5 cases,â…¡-â…¢1 case,â…¢grade 1 case included; The expression of CRFR1 in 3 positive cases of oligodendroglioma were weakly positive, and the pathologic level of gradeâ…¡2 cases,â…¡-â…¢1 case, accounted on the total cases of oligodendroglioma 37.5% (3 / 8); The glioblastoma multiforme tumor in 3 cases whose pathological grade level areâ…£all expressed as moderately positive; The expression of CRFR1 in 2 ependymoma cases was negative,and the pathological levelâ…¡andâ…¢1 case respectively included; 1 case of medulloblastoma expressed as moderately positive; The expression of CRFR1 in glioma had positive correlation with tumor marker MGMT (rs = 0.591 p = 0.001, see Table1)but had no correlation with GFAP (rs =- 0.299 P = 0.108, see Table2), P53 (rs = 0.093 P = 0.624, see Table3), MMP-9 (rs = 0.240 P = 0.201, see Table4) also no correlation with tumor grade (rs =- 0.027 P = 0.888, see Table5); In the Chromophobe pituitary adenoma,tumor cells were round or oval and with smaller nucleolus, nucleus heteromorphism was rare, little cytoplasm and absence of a consistent perinuclear halo, there were no obvious boundaries between cells, most cells arrange diffusely while some of the cells present radial arrangement along fibrous stroma, positive principal of CRFR1 located in the tumor cell membrane, showing a clear yellow or brown, in part of closely packed cells positive principal was connected into a piece,positive expression of CRFR1 also could be seen in the interstitial vascular endothelial cells. 4 of 10 cases of pituitary chromophobe adenoma expressed as positive, including 1 case of TSH adenoma which was weakly positive and 3 cases of prolactinomas expressed as weakly positive to moderately positive, 1 case was negative for the expression of growth hormone adenomas. immunohistochemical analysis showed that U87 glioblastoma cells expressed CRFR1 as strongly positive, RT-PCR results showed that CRFR1 mRNA in U87 cells was in a relatively weak expression.Conclusion:The above types of neural tumors investigated showed that the astrocytomas, oligodendroglioma, glioblastoma multiforme tumor, medulloblastoma had positive expression of CRFR1 while negative in ependymoma, the expression of CRFR1 in gliomas is positively correlated with MGMT, and not correlated with GFAP, P53, MMP-9 and tumor grade. some types of the pituitary chromophobe adenoma such as PRL adenoma and TSH adenoma were in weak to moderately positive expression of CRFR1. In human glioblastoma line U87 CRFR1 is also expressed as positive.