Expression And Significance Of MMR/MSI In Medullary Thyroid Carcinoma And Analysis Of Prognostic Factors

Objective: By detecting the expression of mismatch repair(MMR)protein in medullary thyroid carcinoma(MTC)and determining its microsatellite instability(MSI)according to the negative or positive expression combination of MMR protein,we can understand the potential population of MTC patients who may benefit from anti-programmed death receptor 1(PD-1)/ programmed death ligand 1(PD-L1)immunotherapy.At the same time,the relationship between the expression of MMR/MSI and the clinicopathological features of patients with MTC,as well as the related factors affecting the prognosis of patients with MTC were analyzed.Methods : From November 2009 to November 2019,46 cases of postoperative pathological tissue wax blocks of MTC diagnosed by immunohistochemistry(IHC)after thyroid surgery in Mianyang Central Hospital and surrounding hospitals of Sichuan Province were collected.The expression of mismatch repair protein 1(MutL homolog1,MLH1),mismatch repair protein 2(MutS homolog2,MSH2),mismatch repair protein 6(MutS homolog6,MSH6)and post-meiotic isolate 2(postmeiotic segregation increased2,PMS2)in 46 patients with MTC were detected by IHC,routine MaxVision method.At the same time,the clinicopathological data of 46 patients with MTC were collected retrospectively,and their postoperative survival were followed up.Statistical software and methods were used to analyze the relationship between the status of MMR/MSI and the clinicopathological characteristics of MTC patients,as well as the related factors that may affect the prognosis of MTC patients.Results:(1)Among the 46 patients with MTC,5 patients were diagnosed as dMMR by IHC,accounting for 10.9%(5 / 46),41 patients were diagnosed as pMMR,accounting for 89.1%(41 / 46).The postoperative pathological stages of 5 patients with dMMR were 2 cases of stage ?,2 cases of stage ? and 1 case of ?.The MSI status was classified according to the number of MMR protein deletions,including 41 cases in the MSS group(89.1%),3 cases in the MSI-H group(6.5%),and 2 cases in the MSI-L group(4.3%).The postoperative pathological stages of 3 patients with MSI-(2)H were stage ?(n=1),stage ?(n=1)and stage ?(n=1).There was no significant difference in the expression of MMR/MSI in the clinicopathological features of MTC patients such as age,sex,maximum diameter of the tumor,lymph node metastasis,gland invasion in vitro,location,number of lesions,postoperative pathological stage,distant metastasis,initial operation and lymph node dissection(P>0.05).(3)As of November 2019,the 1-,3-,and 5-year survival rates of MTC patients were 97.7%,92.8%,and 89.0% respectively;univariate analysis showed that MMR status and MSI status were not related to the prognosis of MTC patients,and the difference was not statistically significant(P=0.696,0.467).Invasion of glands in vitro,maximum diameter of tumor,lymph node metastasis,distant metastasis and postoperative pathological stage were related factors affecting the prognosis of patients(P<0.05).Multivariate analysis showed that only distant metastasis or maximum tumor diameter were independent factors affecting the prognosis of patients with MTC(P<0.05).Conclusions:(1)Among the 46 patients with MTC,5 patients with dMMR/MSI-H were detected by IHC method,accounting for 10.9%(5 / 46).It can be understood that anti-PD-1/pd-L1 immunotherapy in MTC patients may have potential benefits,or it may be possible to improve the condition and prolong survival through the use of anti-PD-1/pd-L1 immunotherapy,but this still needs to be practiced in clinical trials and needs to be supported by a large number of clinical studies and statistical data.(2)The basic clinicopathological features of MTC patients,such as age,sex,maximum diameter of tumor,lymph node metastasis,invasion of glands in vitro,location,number of lesions,postoperative pathological stage,distant metastasis,initial operation and lymph node dissection,were not related to the expression of(3)MMR/MSI.The expression of MMR/MSI is not related to the prognosis of patients with MTC.Invasion of glands in vitro,tumor maximum diameter,lymph node metastasis,distant metastasis and postoperative pathological stage are important factors affecting the prognosis of patients with MTC.Maximum tumor diameter and distant metastasis are independent risk factors affecting the prognosis of MTC patients.When the maximum tumor diameter>4cm or with distant metastasis,the prognosis is poor.