The Expression And Clinical Significance Of HMSH2 In Papillary Thyroid Carcinoma And Follicular Thyroid Carcinoma

BackgroundThyroid cancer is the most common malignant tumor in endocrine system,and most of the patients are 40 ～ 50 years old.Differentiated thyroid carcinoma(DTC)is the most common thyroid carcinoma,accounting for 90% ～ 95% of all thyroid carcinomas,including papillary thyroid carcinoma(PTC)and follicular thyroid carcinoma(FTC).PTC is the most common tumor with slow growth and low malignancy,but early local lymph node metastasis.FTC is relatively rare,with high degree of malignancy and poor prognosis.In recent years,it has been found that the mismatch repair gene(MMR)system is closely related to the occurrence and development of tumors.DNA replication or DNA mismatch repair defect(d MMR)can lead to gene mutations,and the accumulation of mutations will lead to Microsatellite instability(MSI),which is closely related to the occurrence and development of tumors.hMSH2 is the first isolated human DNA mismatch repair gene.The gene is homologous to bacterial Mut S and located on the short arm of human chromosome 2.Existing research shows that the mismatch repair gene hMSH2 can move the insertion-deletion loop generated by the primary template when the DNA repeat sequence slips,and correct the single base mismatch that escapes the correct reading,so as to prevent the accumulation of spontaneous mutations and ensure the integrity and stability of DNA replication.However,the related studies mainly focus on papillary thyroid carcinoma,and there are few studies on microsatellite instability in follicular carcinoma,and even fewer comparative studies between them.In addition,gene mutation is the main reason for the generation of new tumor antigens.The more mutations and new antigens accumulated in tumors carrying d MMR,the greater the potential for anti-tumor immunity.It was found that the proportion of d MMR in thyroid cancer patients was as high as 63%,which was the cancer with the highest content of d MMR.This also brings potential value to immunotherapy of thyroid cancer,which needs further research and verification.ObjectiveIn this study,the expression of hMSH2 in PTC and FTC tissue samples was detected,and the expression was statistically analyzed with age,sex,lymph node metastasis,immunohistochemical score and other clinical indicators,to explore the difference and significance of hMSH2 expression in the two,in order to reveal its relationship with the occurrence and development of cancer,biological characteristics and prognosis,and provide theoretical support for clinical prevention and treatment.Methods1.The postoperative cancer tissues of 25 patients and 18 patients with papillary thyroid carcinoma and follicular thyroid carcinoma clinically diagnosed in the First Affiliated Hospital of Luohe Medical College were collected,as well as the patients’ age,sex,combined with Hashimoto’s thyroiditis,lymph node metastasis,distant metastasis,peripheral blood leukocyte count,platelet count,neutrophil count,the number of lymphocytes,monocytes,TG content of medical information.2.Half of the tumor samples were used to prepare wax blocks,and the other half were immediately stored in liquid nitrogen for extracting total RNA.The expression level of hMSH2 was detected by reverse transcription polymerase chain reaction(RT-PCR)and immunohistochemistry(IHC).3.The correlation between hMSH2 immunohistochemical score and clinical indexes of papillary thyroid carcinoma and follicular thyroid carcinoma was analyzed.Results1.hMSH2 m RNA and protein expression levels were higher in PTC tissues than in FTC tissues The expression level of hMSH2 m RNA in 25 PTC tissues was significantly higher than that in 18 FTC tissues(P<0.05),and the strong positive rate of hMSH2 in PTC tissues was significantly higher than that in FTC tissues(P<0.001).hMSH2 of PTC was mainly expressed in the cytoplasm and membrane of thyroid cancer cells,but not in the nucleus.hMSH2 of FTC was expressed in the nucleus,cytoplasm and membrane of thyroid cancer cells.2.There were statistical differences in lymph node metastasis,distant metastasis and hMSH2 immunohistochemical score between PTC and FTC The central lymph node metastasis rate of 25 PTC patients was significantly higher than that of 18 FTC patients(P<0.001),and the distant metastasis rate of FTC patients was significantly higher than that of PTC patients(P<0.001).The hMSH2 immunohistochemical score was higher in PTC than in FTC(P<0.001).3.The hMSH2 immunohistochemical score in PTC patients was positively correlated with clinical grade and lymph node metastasis to the central area Immunohistochemical score of hMSH2 was positively correlated with clinical grade(r=0.428,P=0.033)and lymph node metastasis to the central area(r=0.533,P=0.026)in PTC patients.ConclusionThe expression of hMSH2 in papillary thyroid carcinoma was significantly increased,and its distribution was different from that in follicular thyroid carcinoma.The hMSH2 immunohistochemical score of papillary thyroid carcinoma was positively correlated with clinical grade and lymph node metastasis to the central area.This study has certain guiding significance for the occurrence,development and prognosis of papillary thyroid carcinoma.