Cellular Localization of Beta-Catenin by Immunohistochemistry Is a Sensitive and Specific Surrogate for CTNNB1 Mutational Status in Adrenal Cortical Neoplasms
Alexandra E Kovach, Quynh Lam, Dora Dias-Santagata, Peter M Sadow. Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA
Background: Evaluating adrenal cortical carcinoma (ACC) is a challenge in surgical pathology because of its relative rarity and histologic overlap with adenomas (ACA). We previously performed a molecular screen of adrenal cortical carcinomas and confirmed enrichment of CTNNB1 mutations in these tumors. Here, we compare mutational status of carcinomas with a cohort of adenomas with comparatively benign clinical outcome and to investigate the relationship between mutational status and beta-catenin (BCAT) nuclear localization by immunohistochemistry.
Design: Twenty-one cases of ACC and 11 cases of ACA underwent histologic and clinical review as well as a multiplex nucleotide amplification molecular screen (SNaPshot) from formalin-fixed paraffin-embedded tissue developed in-house of 15 common cancer-associated genes, including common sites for mutation in the beta-catenin (CTNNB1) gene. Immunohistochemistry for BCAT was performed, and sensitivity and specificity for immunohistochemistry to predict mutational status were determined.
Results: By mutational screen, 9/21 carcinomas (43%) had CTNNB1 mutations, 1 with an additional p53 mutation; 1 case with an APC mutation; and the remaining 11 were wild-type for tested loci. Strong nuclear localization of BCAT immunostain corresponded with the presence of CTNNB1 mutation by genotyping in 8 of 9 cases (89% sensitivity); the mismatched case demonstrated strong membranous staining by IHC. Nine of the 12 cases without CTNNB1 mutation by mutational screen showed membranous staining or did not stain (75% specificity). 3 mismatched cases demonstrated scattered (<10%) positive nuclei; 1 of these cases had the APC mutation. 2 of 11 adenomas (18%) demonstrated CTNNB1 mutations by mutational screen, with no mutations identified in the 9 additional cases; this was corroborated immunohistochemistry for BCAT. No histomorphologic parameter appeared dominant in lesions with a particular mutational status.
Conclusions: Mutational status of CTNNB1 in adrenal cortical neoplasms can be predicted with reasonable accuracy by immunohistochemical cellular localization. Larger studies are needed to address whether CTNNB1 mutational status is associated with prognosis of adrenal cortical lesions. Nuclear localization of beta-catenin by immunostain may be helpful in analysis of select lesions of the adrenal cortex whose biologic behavior is uncertain from clinical and histologic information.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 98, Monday Morning