The Role of Immunohistochemical Markers for the Diagnosis and Prognosis of Adrenocortical Neoplasms.

Anna Angelousi,Eva Kassi,Chrysanthi Aggeli,George Zografos,Fani Athanasouli,Georgios Kyriakopoulos,Anastasia Dimitriadi,Gregory Kaltsas

doi:10.3390/jpm11030208

Abstract

Adrenal cortical carcinoma (ACC) is a rare cancer with poor prognosis that needs to be distinguished from adrenocortical adenomas (ACAs). Although, the recently developed transcriptome analysis seems to be a reliable tool for the differential diagnosis of adrenocortical neoplasms, it is not widely available in clinical practice. We aim to evaluate histological and immunohistochemical markers for the distinction of ACCs from ACAs along with assessing their prognostic role. Clinical data were retrospectively analyzed from 37 patients; 24 archived, formalin-fixed, and paraffin-embedded ACC samples underwent histochemical analysis of reticulin and immunohistochemical analysis of p27, p53, Ki-67 markers and were compared with 13 ACA samples. Weiss and Helsinki scores were also considered. Kaplan−Meier and univariate Cox regression methods were implemented to identify prognostic effects. Altered reticulin pattern, Ki-67% labelling index and overexpression of p53 protein were found to be useful histopathological markers for distinguishing ACAs from ACCs. Among the studied markers, only pathological p53 nuclear protein expression was found to reach statistically significant association with poor survival and development of metastases, although in a small series of patients. In conclusion, altered reticulin pattern and p53/Ki-67 expression are useful markers for distinguishing ACCs from ACAs. Immunohistopathology alone cannot discriminate ACCs with different prognosis and it should be combined with morphological criteria and transcriptome analysis.

Highlights

Introduction iationsAdrenocortical carcinoma (ACC) is a highly aggressive malignancy with an estimated worldwide prevalence of 4–12 cases per million adults and a five-year survival rate ranging from 16 to 38% [1,2]
In order to provide prognostic biomarkers for the evaluation of surgical samples with adrenocortical neoplasms, we investigated the role of altered reticulin framework, a fast and cheap technique with high interobserver reproducibility, as well as of proteins involved in cell proliferation and mitotic spindle regulation such as Ki-67, p53, and p27 in a surgical series of benign and malignant adrenocortical neoplasms
We retrospectively examined 24 Adrenal cortical carcinoma (ACC) and 13 adrenocortical adenoma (ACA) samples obtained from the archival files of 37 patients submitted to adrenal surgery (Table 1)

Summary

Introduction

Adrenocortical carcinoma (ACC) is a highly aggressive malignancy with an estimated worldwide prevalence of 4–12 cases per million adults and a five-year survival rate ranging from 16 to 38% [1,2]. Several different scoring systems have been proposed to assess the malignant potential in adrenocortical neoplasms, the Weiss score remains the most utilized tool in distinguishing benign from malignant adrenocortical neoplasms [3]. This score counts nine histopathologic criteria: eosinophilic (“dark”) cytoplasm in more than 75% of tumor cells, a “patternless” diffuse architecture, necrosis, nuclear atypia, mitotic index above 5 per 50 high-power fields, atypical mitoses, sinusoidal, venous, and capsular invasion [4]. The distinction of noninvasive lowgrade ACC with a low Weiss score from adrenocortical adenoma (ACA) poses a diagnostic

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