Diagnostic Role Of Steroidogenic Factor-1 And Prostate-specific Membrane Antigen In Adrenocortical Carcinoma

Objective:Adrenocortical carcinoma(ACC)is a rare and invasive cancer that occurs in the adrenal cortex with few treatments and poor prognosis.When considering the malignant tumors,we cannot determine whether it originates from the adrenal gland or from other sites.In recent years,immunohistochemical staining methods for diagnosing adrenocortical carcinoma are becoming more and more popular.Among these immunohistochemical markers,prostate-specific membrane antigen(PSMA)and steroidogenic factor-1(SF-1)are the most helpful markers.What’s more,PSMA is highly valued as a therapeutic target.The purpose of this study is to investigate if these two markers are helpful to differentiate ACC from adrenocortical adenomas(ACA),and to compare the clinical and pathological characteristics of patients with different expression strengths of these two markers and to verify their function of predicting the prognosis of patients.Finally,we explore the role of these two markers in differentiating primary adrenocortical carcinoma from adrenal metastases in other sites.In order to reduce the misdiagnosis rates and provide a new method for diagnosis and treatment.Methods:A total of 150 cases were selected who had undergone surgery for an adrenocortical tumor at our hospital between June 2005 and June 2016.PSMA and SF-1 expression was assessed by immunohistochemistry on tissue samples from 50 ACC,90 ACA(including 20 cortisol-producing adenomas,20 aldosterone-producing adenomas and 50 non-functional tumors)and 10 tissues that were metastases from other primary sites.We defined the grade of intensity as follows:0,negetive;1,low positive;2,positive;3,high positive.We define the score of density as follows:0,0%;1,26%-50%;2,51%-75%;3,76%-100%.We combined intensity and density to get composite staining score:0,negetive;1-3,positive;>3 high positive.We compared clinical and pathologic characteristics,analyzed positive rate,intensity and density,compared the clinical and pathological characteristics of patients with different expression strengths of these two markers,and conducted the prognostic role of these markers.Results:The clinical and pathologic features revealed that the size of ACC was bigger than ACA and the age of ACC was also elder than ACA(P<0.01).The percentage of PSMA-positive vessels,mean intensity,mean density and the composite staining score were found to be significantly less in ACA when compared with ACC(p<0.01).SF-1 protein expression was detected in 80 of 90 ACA cases(88%),while 30 of 50 ACC cases(60%)(p<0.01).The positive rate,mean intensity,mean density and composite staining score of SF-1 among ACA cases was much higher than ACC(p<0.01).All of these markers were negative among metastases.The results also showed that the high Ki-67 index is associated with a high SF-1 composite score,and the high ENSAT stage and high Ki-67 index are associated with a high PSMA composite staining score.However,according to the survival distribution curve,there is no necessarily relationship between the high-intensity PSMA group and poor prognosis.Patients with a PSMA composite staining score of>3 were 75 times more likely to be diagnosed with malignancy than other patients.The best diagnostic cutoff-point for PSMA was 3.5,with a sensitivity of 46%and a specificity of 99%.Conclusions:In this study,PSMA is a good marker at distinguishing ACC from ACA.The higher grade of PSMA expression rate is associated with a higher tumor ENSAT stage and a higher rate of Ki-67 index,so it can be used to predict prognosis.At the same time,PSMA could be used as a new treatment method.SF-1 didn’t show as a helpful tool in differentiating ACC and ACA,but SF-1 was specifically expressed in the adrenal glands,and it could be used to identify functional and nonfunctional tumors.What’s more,nonfunctional tumors got the highest score.The high Ki-67 index is associated with a high SF-1 composite staining score,so SF-1 can indirectly predict the prognosis of patients with ACC.SF-1 and PSMA may become new methods for differentiating adrenocortical carcinoma from adrenal metastases.