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Beta-Catenin in Adrenocortical Neoplasms

DISCOVERIES (ISSN 2359-7232), 2015

CITATION: 

Kovach AE, Nucera C, Lam QT, Nguyen A, Dias-Santagata D, Sadow PM. Genomic and immunohistochemical analysis in human adrenal cortical neoplasia reveal beta-catenin mutations as potential prognostic biomarker. Discoveries 2015, 3(2): e40. DOI: 10.15190/d.2015.32

 Submitted: January 21, 2015; Revised: February 25, 2015; AcceptedMarch 10, 2015Published: March 20, 2015;

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Genomic and immunohistochemical analysis in human adrenal cortical neoplasia reveal beta-catenin mutations as potential prognostic biomarker

Alexandra E. Kovach (1,#), Carmelo Nucera (2,#), Quynh T. Lam (1), Ahnthu Nguyen (1), Dora Dias-Santagata (1), Peter M. Sadow (1,*)


(1) Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;
(2) Laboratory of Human Thyroid Cancers, Preclinical and Translational Research, Division of Cancer Biology and Angiogenesis, Cancer Research Institute (CRI), Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;

# These authors contributed equally to this work;

*Correspondence to: Peter M. Sadow MD, PhD, Pathology Service, WRN219, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114; psadow@mgh.harvard.edu;

Abstract

Evaluation for malignancy of the adrenal cortex, adrenal cortical carcinoma (ACC), is a challenge in surgical pathology due to its relative rarity and histologic overlap with its benign counterpart, adrenocortical adenoma (ACA). We characterized a cohort of human ACC and ACA, including a molecular screen, with a goal of identifying potential diagnostic adjuncts. Thirty-six cases of ACC underwent histologic and clinical review.  In the 31 ACC cases with available material and a cohort of 10 ACA cases, a multiplex nucleotide amplification molecular screen from formalin-fixed, paraffin-embedded tissue was peformed. ACCs demonstrated a wide variety of clinical and histologic characteristics with overall poor but unpredictable survival for subjects with ACC. By mutational screen, 12/31 (38.7%) carcinomas harbored CTNNB1 mutations, 1 with an additional TP53 mutation; 1 case each had isolated APC and TP53 mutations; 16 were wild-type for all tested loci; and 1 case demonstrated repeated assay failures.  Two of the 10 ACA (20%) demonstrated CTNNB1 mutations by mutational screen, with no additional mutations.  Immunohistochemistry for beta-catenin was performed and compared with the results of the molecular screen. Strong nuclear beta-catenin immunopositivity corresponded to the presence of CTNNB1 mutation by genotyping in 10 of 12 cases (83% sensitivity); the mismatched case(s) demonstrated strong membranous staining by immunohistochemistry. Seventeen of the 18 cases without CTNNB1 mutation showed membranous staining or did not stain (94% specificity); the mismatched case demonstrated scattered (<10%) positive nuclei. Both mutations in ACA were corroborated with immunohistochemistry for beta-catenin. No histomorphologic parameter appeared dominant in lesions with a particular mutational status.  Based on these results, mutational status of CTNNB1 in adrenal cortical neoplasms can be predicted with reasonable accuracy by immunohistochemical cellular localization.  Nuclear localization of beta-catenin by immunostain may be helpful in analysis of select lesions of the adrenal cortex whose biological behavior is uncertain from clinical and histologic information; a larger cohort is required to test this hypothesis.

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