Abstract

Simple SummaryCarcinoma of the cortical region of the adrenal (ACC) is a rare and aggressive cancer often with poor prognosis and limited therapies. For these reasons, tumor markers for early diagnosis and monitoring the therapy and tumor evolution are required. This paper demonstrates in a cohort of 19 patients affected by ACC, that in a simple blood draw (liquid biopsy), different cells associated with the tumor can be found in samples taken before and after surgery. Among them, the number of circulating tumor cells in blood samples taken before surgery can be predictive of the patients’ survival and tumor recurrence, thus contributing valuable information on the tumor, which may contribute to improve patient management and follow up. Further studies on larger cohorts of ACC patients are required to validate this novel finding.Adrenocortical carcinoma (ACC), a rare and aggressive neoplasia, presents poor prognosis when metastatic at diagnosis and limited therapies are available. Specific and sensitive markers for early diagnosis and a monitoring system of therapy and tumor evolution are urgently needed. The liquid biopsy represents a source of tumor material within a minimally invasive blood draw that allows the recovery of circulating tumor cells (CTCs). CTCs have been recently shown to be detectable in ACC. In the present paper, we evaluated the prognostic value of CTCs obtained by size-filtration in a small pilot cohort of 19 ACC patients. We found CTCs in 68% of pre-surgery and in 38% of post-surgery blood samples. In addition, CTC clusters (CTMs) and cancer associated macrophages (CAMLs) were detectable in some ACC patients. The median number of CTCs significantly decreased after the mass removal. Finally, stratifying patients in high and low pre-surgery CTC number groups, assuming the 75th percentile CTC value as cut-off, CTCs significantly predicted patients’ overall survival (log rank = 0.005), also in a multivariate analysis adjusted for age and tumor stage. In conclusion, though preliminary and performed in a small cohort of patients, our study suggests that CTC number may represent a promising marker for prognosis and disease monitoring in ACC.

Highlights

  • Adrenocortical carcinoma (ACC) is a rare aggressive and heterogeneous neoplasia, with an evolution strictly depending on early diagnosis, as the five-year survival in the metastatic forms drops down to 0–28% according to the different series [1]

  • We have previously demonstrated the specific presence of circulating tumor cells (CTCs) in ACC, suggesting that they may represent a good marker for this tumor [8]

  • CTC positivity for steroidogenic factor-1 (SF-1) was detected by immunocytochemistry performed in parallel filters obtained from the same blood sample used to confirm CTC adrenocortical origin

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Summary

Introduction

Adrenocortical carcinoma (ACC) is a rare aggressive and heterogeneous neoplasia, with an evolution strictly depending on early diagnosis, as the five-year survival in the metastatic forms drops down to 0–28% according to the different series [1]. The challenge in the management of advanced adrenocortical carcinoma depends on the paucity of the pharmacological approaches [1], which are limited to mitotane (MTT) alone or combined with etoposide, doxorubicin and cisplatin (EDP) treatment [2], with a variable range of efficacy This still makes the radical resection of the mass the best therapeutic option for early stage resectable ACC [3]. Among the tumor material recovered, circulating tumor cells (CTCs) have gained importance in the oncology field as biomarkers of the tumor development [6] They are the most informative marker of the tumor status and of the invasive/metastatic potential, as they might contain cells able to trigger the metastatic process [7]

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