A study of the TP53 Germline Mutation and Clinicopathologic Features in Thai Children with Adrenocortical Carcinoma

Objective: To determine the clinicopathologic features and germline tumor protein p53 (TP53) mutation in children with adrenocortical carcinoma (ACC). Material and Methods: This was a retrospective study. From 2009 to 2018, children with ACC from King Chulalongkorn Memorial Hospital and Phramongkutklao Hospital were enrolled into the study. Clinical presentations and hormonal profiles were recorded. Mutation analyses of the  TP53  gene were acquired using the next-generation-sequencing method which was performed for germline samples of all patients and the parents of those who tested positive. Result: Two males and six females with ACC were enrolled into this study. The median age at diagnosis was 25.5 months (range 10 to 67 months). All participants had virilization, either virilization only (n=3) or associated with Cushing (n=5). All participants had had surgery to completely remove all of the tumor and three participants had received adjuvant chemotherapy consisting of etoposide, doxorubicin, and cyclophosphamide. All participants had three different known mutations in the  TP53  gene: c.1010G>A (p.R337H), c.916C>T (p.R306*) and c.743G>A (p.R248Q). Two of the three participants with  TP53  mutations had pulmonary metastasis. One participant had wild-type TP53 and pulmonary recurrence occurred one year after diagnosis. The median follow-up time was 31 months (range 10 to 168 months. As of this writing, seven participants survived without evidence of recurrence. No second malignancy was found in all participants. One participant who had c.916C>T died of pulmonary metastasis 10 months after diagnosis. Conclusion:  We successfully identified three different germline  TP53  mutations in patients with ACC. Progression to pulmonary metastasis and recurrence were higher among participants with  TP53  mutations. The treatment outcome of childhood ACC was good when surgery and adjuvant chemotherapy were used.