Elsevier

Cancer Genetics

Volume 205, Issue 4, April 2012, Pages 131-137
Cancer Genetics

Review
The molecular basis of adrenocortical cancer

https://doi.org/10.1016/j.cancergen.2012.02.009Get rights and content

Adrenocortical tumors (ACTs) are common, and most are benign adrenocortical adenomas (ACAs). Malignant adrenocortical carcinoma (ACC) is a rare tumor type and is observed at the rate of one or two cases per million annually. ACTs are classified as either ACAs or ACCs by histopathologic methods that are based on nine Weiss scoring criteria, including the nuclear grade, mitotic rate, presence of necrosis, and others. In this review, we describe the findings of studies that have examined the molecular basis of ACTs, and we compare transcriptome analysis with other diagnostic approaches. ACTs are occasionally difficult to classify. Therefore, molecular techniques, such as microarray analysis, have recently been applied to overcome some of these diagnostic problems. We also discuss the likelihood of the diagnosis and discernment between ACAs and ACCs based on the molecular tests. To show the recent progress in understanding the etiology of ACTs, we highlight the relationship between genetic analysis and transcriptome analysis. We attempt to understand the role of abnormal cell growth and steroid hormone secretion. Genetic and transcriptome analyses have improved our understanding of ACTs considerably, yet many unanswered questions remain.

Section snippets

Diagnosis

Most frequently, malignant tumors in the adrenal glands are formed from the metastasis of cancers that have initiated growth in other organs, largely the lungs and breast. Most nonmetastatic adrenal masses are asymptomatic, benign tumors called adrenocortical adenomas (ACAs). The adrenocortical tumors (ACTs) revealed during diagnostic procedures for unrelated disorders are called incidentaloma (1). Most ACAs are likely undiagnosed, and among all diagnosed ACAs, 52% are subsequently removed

Genetics of adrenocortical tumors

Various analyses were applied to characterize the genetic background of ACA and ACC and to distinguish between both types of tumors. Comparative genomic hybridization (CGH) analysis has shown that the accumulation of chromosomal aberrations correlates with the size of a tumor (31).

The loss or gain of chromosomes 17 and 9 was observed in 28–75% of ACA cases 31, 32, 33, 34, 35. The most frequent aberrations (39–47%) in ACC cases were the amplification of chromosomes 5 and 12 and the loss of

Treatment

The treatment strategies for ACCs include resection with or without adjuvant therapy or radiotherapy. Tumors diagnosed in stages I–III by imagining techniques are removed surgically. Surgery may also be considered for stage IV tumors, yet the therapy depends on the metastasis of the cancer. The overall 5-year survival rate after tumor resection has been estimated at 35% 65, 66. The elimination of an adrenocortical tumor in stage IV could diminish steroid hypersecretion and improve the

Future considerations

ACA and ACC tumors are highly heterogeneous. It remains a goal to design a reliable method to distinguish between benign ACA and malignant ACC based on differences among the transcriptomes. However, transcriptome analysis has revealed many abnormalities in gene expression. Additionally, the primary cause of adrenocortical cancer is still unclear. The prognostic value of the mRNA-based test is also limited. These types of cancers, such as ACC, require international coordinated cooperation to

Acknowledgments

We thank Ms. Beata Raczak and M.Sc. Bogumiła Ratajczak for their indispensable help during the preparation of this manuscript.

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