Expression of β-Catenin in Thyroid Neoplasms (Histopathological and Immunohistochemical Study)

Abstract

Background: Thyroid cancer is the most common malignant tumor of the endocrine system accounting for more than 90% of all endocrine cancer and 63% of all endocrine cancer deaths. β-catenin is a multifunctional protein that  plays a key role in Wnt (wingless type) pathway and influences the expression of different genes and their proliferation, thus making it a potential therapeutic target. Aim of Work: This work aimed to examine immunohistochemical expression of β-catenin in different cases of thyroid neoplasms and to correlate between β-catenin expression and clinicopathological features of these thyroid neoplasms. Methods: This retrospective study was conducted on sixty cases of archived, formalin fixed, paraffin embedded tissue blocks that included different histologic types of thyroid neoplasms. Immunohistochemistry  using β-catenin monoclonal antibody was performed using a standard avidin-biotin-peroxidase system. β-catenin expression was quantified both at membranous and cytoplasmic level.  Immunostaining scores were based on the staining intensity (I) and the percentage of positive cells (P). β-catenin final score (H score) resulted by summation of I and P (ranging from 0 to 7). Cases with H score between 1–3 were considered with low score and cases with H score between 4–7 were considered with high score. Results:  Of the malignant thyroid neoplasms in the studied cases, 81% showed positive β-catenin expression with the majority (86%) of the benign thyroid cases showing positive expression.  Both membranous and cytoplasmic staining were both assessed in which the majority of the negative and high positive membranous cases also showed the same interpretation for cytoplasmic β-catenin expression.  Positive correlations were  proved between β-catenin expression of diagnosed malignant cases, (pvalue =0.042) where all hurthle cell, follicular and medullary carcinoma cases, 87.5% of studied papillary carcinoma cases and 50% of poorly differentiated carcinoma cases showed β-catenin positivity while all anaplastic carcinoma cases were negative. Furthermore, statistically significant findings were seen in cases with absence of extrathyroid extension (P value= 0.045) especially those displaying β-Catenin cytoplasmic expression with extrathyroid extension of studied malignant cases showing  a P value= (0.011) . No significant correlation was found between β-catenin expression and patients' pathological diagnosis, gender, extent of primary tumor (pT), lymph node metastasis, multifocality and co-existing pathology among studied malignant cases. Conclusion: The present study suggests the prognostic role of β-catenin and its possible usage to identify patients who may benefit from adjuvant β-catenin targeted mono- or combined therapy for tumors expressing this protein, especially for thyroid cases that cannot be removed surgically or that do not respond to traditional treatment options.   Key Words: β-catenin, immunohistochemistry, malignant thyroid neoplasms, benign thyroid neoplasms.