Predictive role of leptin and cyclin D1 in papillary thyroid carcinoma: an immunohistochemical study

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Abstract

Introduction

Thyroid carcinoma is one of the most common malignancies originating from endocrine organs. Among various histological types of thyroid carcinoma, papillary thyroid cancer (PTC) is the most common. Obesity has long been recognized as a risk factor for tumorigenesis. Compelling evidence suggests leptin as a potential link between obesity and cancer development. Leptin can act as a mitogen and an angiogenic factor in several types of cancer. Cyclin D1 proto-oncogene regulates G1 to S-phase transition in the cell cycle in different tissues, and overexpression of cyclin D1, associated with amplification of the CCND1 gene, has been reported in esophageal, lung, breast, and head and neck carcinomas.

Aim

The aim of this study was to determine the expressions of leptin and cyclin D1 in PTC so as to evaluate the role of obesity in the pathogenesis of this disease.

Materials and methods

This study was carried out using 67 thyroid specimens, which included 52 specimens of classic PTC and 15 specimens of multinodular goiter as a control group. Immunohistochemical staining was performed to study leptin and cyclin D1 expressions.

Results

Both leptin and cyclin D1 expressions were positive in thyroid carcinoma cases but not in the control group. There was a statistically significant association between positivity of leptin expression and advanced stage (P=0.000) and presence of lymph node invasion (P=0.003). There was a statistically significant association between high cyclin D1 expression and presence of extrathyroid extension (P=0.011), advanced stage (P=0.000), and presence of lymph node invasion (P=0.000). There was also an association between low expression of cyclin D1 and presence of thyroiditis. There was a significant relationship between positivity of leptin expression and diffuse cyclin D1 expression.

Conclusion

We conclude that the expressions of leptin and cyclin D1 in PTC are associated with neoplasm aggressiveness, including advanced stage and presence of lymph node metastasis. Absence of both leptin and cyclin D1 expressions in normal noncancerous follicular cells and multinodular goiter cases indicates their role in early carcinogenesis of PTC. Novel opportunities could emerge from the discovery of leptin crosstalk with other oncogenic pathways, inflammatory and angiogenic cytokines, and links to obesity-related cancers.

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