Clinicopathological features, biochemical and molecular markers in 5 patients with adrenocortical carcinoma

Abstract

AdrenocorticAl carcinoma (ACC) is a very rare neoplasm (incidence: 1-2/million) [1], which easily metastasizes to liver, lung, and bone, with a poor prognosis. With the recent advances in various imaging procedures, the detection of incidental adrenal mass has become more frequent, of which 2 to 12% are accounted for by ACC [2,3]. Therefore, it becomes more important to differentiate ACC from benign tumors such as adrenocortical adenomas (ACA). Functioning ACC Abstract. Adrenocortical carcinoma (ACC) is a very rare malignant tumor with poor prognosis. To gain insight into the pathogenic significance of ACC, we studied clinicopathological features and gene expression profile in ACC. We analyzed five ACC cases (two men and three women) with the median age of 45-year-old who underwent adrenalectomy at our institute. Endocrine studies revealed that two cases had subclinical Cushing's syndrome (SCS) and one with concomitant estrogen-secreting tumor, while the rest of three cases had non-functioning tumors. Analysis of urinary steroids profile by gas chromatography/mass spectrometry showed increased metabolites of corticosteroid precursors, such as 17-OH pregnenolone, 17-OH progesterone, dehydroepiandorosterone (DHEA), and 11-deoxycortisol in all five cases. The pathological diagnosis of ACC was based on Weiss's criteria with its score ≥ 3. The mean size of the resected tumors was 87 mm and Ki67/MIB1 labeling index, a proliferative marker, was 3 -27%. Immunohistochemical analysis revealed a disorganized expression of several steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, and DHEA-sulfotransferase. Among several genes determined by RT-PCR, insulin-like growth factor (IGF)-II mRNA was consistently and abundantly expressed in all 5 tumor tissues. Postoperatively, two cases with SCS developed local recurrence and liver metastasis. The present study suggests that the disorganized expression of steroidogenic enzymes and the overexpression of IGF-II by the tumor are hallmarks of ACC, which could be used as biochemical and molecular markers for ACC.

Diagnostic and prognostic role of SF1, IGF2, Ki67, p53, adiponectin, and leptin receptors in human adrenal cortical tumors

“…According to some authors, complementing the histopathological examination with an immunohistochemical staining for Ki67 aides in establishing the diagnosis of ACC, while p53 may be a recommended marker of higher malignancy . Also, high Ki67 expression seems to be present in patients with metastasizing ACC with poor prognosis …”

“…It was found in vitro that the IGF2 gene induces neoplastic cell proliferation in ACC via IGF1 receptor, which points at a role of the IGF‐system in adrenocortical carcinogenesis . For that reason, IGF2 expression may be associated with a very malignant ACC phenotype . This relationship has been applied in novel antineoplastic therapy …”

“…The histopathological diagnosis is difficult at times and does not allow to clearly differentiate between ACC and ACA. In the present study, patients were selected, whose histopathological diagnosis was certain and who were followed-up for [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] We assessed immunohistochemical staining for acknowledged parameters, that is, Ki67, p53, SF1, IGF2, as well as so far unexamined adipokine antibodies Adipo R1, R2, and leptin Ob-R in malignant and benign adrenal cortex tumors.…”

“…15 For that reason, IGF2 expression may be associated with a very malignant ACC phenotype. 15 This relationship has been applied in novel antineoplastic therapy. 26 It is unclear whether an increase in IGF2 expression modifies ACC biology.…”

Significance of heparanase-1 and vascular endothelial growth factor in adrenocortical carcinoma angiogenesis: potential for therapy

“…Histological features, including high mitotic rate, atypical mitoses, high nuclear grade, low percentage of clear cells, necrosis, diffuse architecture of tumor, capsular invasion, sinusoidal invasion, and venous invasion, are carefully analyzed according to the method of Weiss [20]. The pathological diagnosis of ACC was based on Weiss's criteria with its score C3 [21]. Forty-four patients of sporadic adrenocortical tumors (ACTs), who underwent adrenalectomy at Ruijin hospital between October 1986 and March 2010, were classified as ACAs (N = 20) and ACCs (N = 24).…”