| Part 1:Analysis on data of clinical characteristic,diagnosis,therapy and postoperative prognosis of adrenocortical carcinoma.Objective:Aim to explore the clinical characteristic of adrenocortical carcinoma,and to explore the influence of surgical approaches on the oncologic prognosis of adrenocortical carcinoma by comparing short-term prognosis of patients undergoing open adrenalectomy with laparoscopic adrenalectomy.Material and methods:We retrospectively analyzed the clinical characteristics of 89 patients diagnosed with ACC,and baseline characteristics,perioperative data and short-term prognosis of 42 patients with stage ?-? ACC,receiving OA(n=22)and LA(n=20)as primary therapy.The primary end point was the first recurrence.Results:Morbidity of ACC in female was a little higher than that in mail,and ages of patients were 40-60 years old.Non-endocrine functional tumors were the main type of ACC,followed by tumors secreting cortisol.The main stages of tumors were stage ?-?,and 40%ACC patients could not accept surgical treatment at the time of primary diagnosis.ACC patients with R0 resection had longer DFS than those without R0 resection.OA group had larger mean maximum diameter of tumor(10.1±3.6 versus 6.3±2.2 cm)and lesser benefits in operative time,bleeding loss and postoperative hospital stay than laparoscopic group.Mean disease-free survival(DFS)of OA was 44.8±35.1 months,which was longer than 17.5±10.4 months of LA(P=0.023),and the rate of 2-year DFS after primary surgery in the open group was higher than in the laparoscopic group(61.1%versus 21.4%,respectively).Rates of 1-year and 3-year DFS showed no significant difference.All patients undergoing LA(11/11)showed local recurrent lesions at the first time of recurrence,while 5 of 13 patients undergoing OA did not show local recurrence(P=0.030).The max diameter of tumors of OA group was negatively related with DFS.Conclusion:Non-endocrine functional tumors were the main type of ACC,and the main stages of tumors were stage ?-?,and 40%ACC patients could not accept surgical treatment.OA for adrenocortical carcinoma is superior to laparoscopic approach in terms of DFS and rate of 2-year DFS,in spite of the larger maximum diameter of tumors and lesser benefit during perioperation.After LA,patients are more likely to show local recurrent lesions at the first time of relapse.R0 resection,surgical approaches and max diameter of tumors may be related with the DFS of ACC patients.Part 2:Experimental research on the gene mutation of adrenocortical carcinoma(ACC)Objective:To explore the condition of gene mutation in tissues of adrenocortical carcinoma,according to the application of objective gene exon capture sequencing.In addition,we compare the data of ACC with the data of benign adrenal adenoma,normal adrenal gland and AIMAH,in order to explore the differential diagnosis for ACC.Material and methods:52 cases of tissues of ACC,32 cases of tissues of benign adrenal adenoma,25 cases of tissues of normal adrenal gland and 28 cases of tissues of AIMAH were collected for objective gene exon capture sequencing.We choose the TP53,CTNNB1,ARMC5,PRKAR1 A,ZNRF3,RB1,APC,MEN1,RPL22,NF1,and ABRC(a new gene mutation found in our recent research on adrenal gland,we use ABRC to describe it due to data security before publish)as target genes.We choose the significant gene mutation and mutation sites by bioinformatics analysis,in order to explore the condition of gene mutation of ACC.And we compare the data of mutation of ACC with that of other groups.Results:6 unqualified cases of ACC were excluded,and there are 131 cases of tissues passed the quality control.There were totally 194 gene mutations and 365 mutation sites found in 46 cases of ACC,and the median number of gene mutation and the median number of mutation sites were 3.50(2.00-6.25)and 5.00(2.75-12.25)respectively,which were significant higher than those of other 3 groups.Rate of target gene mutation in tissues of ACC were NF167.4%(31/46),MEN1 54.3%(25/46),ABRC 47.8%(22/46),ZNRF3 45.7%(21/46),ARMC5 41.3%(19/46),TP53 41.3%(19/46),CTNNB1 32.6%(15/46),APC 26.1%(12/46),RB1 26.1%(12/46),PRKAR1A19.6%(9/46)and RPL22 19.6%(9/46),and the main type of mutation site of ACC was nonsynonymous SNV.ZNRF3,ARMC5,TP53,APC,RB1,PRKAR1A,ABRC,and NF1 with nonsynonymous SNV were defined as high risk gene associated with ACC,of which the rates of mutation were significant higher than that of benigh adrenal adenoma.In addition,sum of high risk mutation sites>3 could be a reference index for the differential diagnosis for ACC with adrenal adenoma.And the sum of high risk mutation sites was positively related with Ki-67 index of tissues of ACC.Conclusions:ZNRF3,ARMC5,TP53,APC,RB1,PRKAR1A,ABRC and NF1 with nonsynonymous SNV were defined as high risk gene associated with ACC.And the rates of mutation of high risk gene were higher than other benign tissues.The sum of high risk mutation sites ?3 could be a reference index for the differential diagnosis for ACC.And the sum of high risk mutation sites was positively related with Ki-67 index of tissues of ACC. |
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