Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare endocrine tumor, and most cases present with hormone excess with poor prognosis. Our research aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression using large cohorts of ACC patients. Immunohistochemistry was used to assess the expression of GR in 78 ACC cases from the West China Hospital (WCH) cohort. RNA-seq data were retrieved from The Cancer Genome Atlas database (TCGA, n=79). Clinicopathological and follow-up data were obtained from two cohorts. The correlation between the GR gene and tumor immune status was estimated using TIMER and GEPIA2. Kaplan-Meier analysis was performed to identify the prognostic value of GR in ACC. In the WCH cohort, positive nuclear GR staining was identified in 90% of the primary ACC cases. Cortisol-secreting ACCs demonstrated significantly lower GR protein expression than did nonfunctioning tumors (P<0.001). This finding was validated by the mRNA data analysis of the TCGA cohort (P = 0.030). GR expression was found to be positively correlated with the immune cell infiltration level and immune-checkpoint-related gene expression in ACC. Survival comparison and multivariate analysis showed that GR expression is an independent prognostic predictor of disease-free survival and overall survival in ACC patients in both cohorts. Our findings suggest that low GR expression is significantly correlated with excess cortisol, immune signatures and poor survival in ACC patients. We propose that GR signaling may play an important role in ACC behavior and thus may be a therapeutic target, which deserves further research.

Reoperation for Recurrent Adrenocortical Carcinoma: A Systematic Review and Pooled Analysis of Population-Based Studies.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare neoplasm with a high recurrence rate. This study aimed to assess the role of surgery in the clinical management of recurrent ACC. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched, and the hazard ratios were pooled. RESULTS: Patients who underwent resection for recurrence had significantly better OS or OS after recurrence than those who received only nonsurgical treatments (HR 0.34, p < 0.001). Prognostic factors were associated with decreased OS after recurrence, including multiple recurrence (HR 3.23, p = 0.001), shorter disease-free interval (HR 2.94, p < 0.001), stage III-IV of the original tumor (HR 6.17, p = 0.001), sex of male (HR 1.35, p = 0.04), and initial non-R0 resection (HR 2.13, p = 0.001). Prolonged OS after recurrence was observed in those who experienced incomplete resection (HR 0.43, 95% CI 0.31-0.52, I2 = 53%) compared with patients who only received nonsurgical treatments. In the reoperated group, patients who underwent complete resection of recurrence had a prolonged OS after recurrence compared with those who underwent incomplete resection (HR 0.23, p = 0.004). CONCLUSIONS: We confirmed the role of reoperation in the clinical management of recurrent ACC. Select patients might benefit from debulking surgery. The preoperative evaluation of the complete resection of the recurrence is the key means to decide whether patients should undergo surgery. Other prognostic factors associated with prolonged OS include single recurrence site, relatively longer disease-free interval, stage I-II of the original tumor, and female sex.

Operative intervention for recurrence of adrenocortical carcinoma: A single-center experience.

INTRODUCTION: Adrenocortical carcinoma is a rare endocrine malignancy with a high recurrence rate. The aim of this study was to evaluate the role of surgery for patients with local or distant recurrent adrenocortical carcinoma and to attempt to identify prognostic features related to survival benefit in patients undergoing resection of recurrence. METHODS: The data of 47 patients with recurrent adrenocortical carcinoma in West China Hospital, Sichuan, China, between 2009 and 2019 were retrospectively collected. These patients were divided into 2 groups according to whether resection of recurrence was performed. The correlation between overall survival after recurrence and reoperation was evaluated. Kaplan-Meier and univariate/multivariate Cox regression methods were used to identify any prognostic factors. RESULTS: Included in our study were 21 patients who underwent reoperation and 26 patients who underwent nonoperative treatments were. The operation group had a better median overall survival after recurrence than the nonoperation group (19 months versus 6.5 months; P = .007). In the operated group, disease-free interval >12 months (P = .002), complete resection of recurrent adrenocortical carcinoma (P = .041), and R0 resection of the primary tumor (P = .005) were associated with prolonged survival after recurrence. CONCLUSIONS: Reoperation plays an important role in the management of selected patients with recurrent adrenocortical carcinoma. Disease-free interval, preoperative evaluation for complete resection, and R0 resection of the primary tumor are important prognostic characteristics for the resection of recurrent adrenocortical carcinoma. The overall survival after recurrence was significantly improved for patients who had a disease-free interval >12 months, and initial R0 resection or complete resection of recurrent adrenocortical carcinoma is feasible.

The aldosterone index could be used to diagnose the dominant gland in primary aldosteronism - a retrospective study.

INTRODUCTION: Failed cannulation in the right adrenal vein, which makes the sampling results in the contralateral vein and inferior vena cava (IVC) nonsense, is the main obstacle of using adrenal vein sampling (AVS) in the lateralisation diagnosis in primary aldosteronism (PA). We performed a retrospective study to evaluate the specificity and sensitivity of using the aldosterone index (AI) in PA lateralisation diagnosis. MATERIAL AND METHODS: We enrolled 116 patients who were diagnosed with PA and then underwent AVS in the West China Hospital of Sichuan University from April 2015 to April 2017. The AI, calculated by dividing the aldosterone concentration of the failed side by the aldosterone concentration of IVC, was used for lateralisation diagnosis if the cannulation was judged to be failed by traditional method. Patients with dominant adrenal gland based on successful AVS were included in subgroup 2 (n = 75), while the patients diagnosed with a dominant gland using AI method were enrolled in subgroup 1 (n = 41). RESULTS: No significant difference of clinical and biochemical findings between the two groups was detected (p value after operation > 0.05). ROC analysis was performed to test the specificity and sensitivity based on the AI in subgroup 2. The AUC for dominant gland detection was 0.76, which resulted in 91.3% sensitivity and 67.53% specificity. The positive and negative likelihood ratios were 2.81. CONCLUSIONS: Our data suggested that the modified strategy using AI to diagnose the dominant gland in PA is an efficient method when cannulation has failed in the right side.