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Prognostic significance of cyclin D1 and p27 in papillary microcarcinoma of the thyroid gland

Papillary thyroid carcinoma (PTC) is the most frequent thyroid neoplasm. Despite its well- differentiated characteristics, PTC often spreads to cervical lymph nodes. Favorable features are female sex, age under 45, small tumor (<2 cm), and tumors limited to the gland. Thyroid papillary microcarcinoma (PMC) is a papillary carcinoma that measures 1 cm in maximum dimension. This type is usually found accidentally, in surgical specimens of benign lesions. On rare occasions, PMC behaves aggressively. That is the reason why it is important to identify patients at a high risk. Surgery is the cornerstone of PTC therapy and total thyroidectomy (TT) is indicated in patients at higher risk. The NCCN panel members have suggested that total thyroidectomy in PMC may not be needed. Cyclin dependent kinases (CDK) play an important role in metastasizing of thyroid carcinomas. They activate cell cycle through complexes with cyclins. P27 is a tumor suppressor that acts as a CDK inhibitor. Cyclin D1 overexpression and p27 underexpression predict a more aggressive behavior of large papillary carcinomas. We tested the hypothesis that cyclin D1 overexpression and p27 underexpression could identify a subgroup of PMC with metastatic potential. The study included 65 patients with PMC. Data on patient age, sex, tumor size (mm), tumor multifocality and status of regional lymph nodes (LN) were collected from the pathology reports. Total thyroidectomy was performed in 23 patients and TT with paratracheal dissection was performed in 39 patients. Immunohistochemical expression of cyclin D1 and p27 was evaluated as a percentage of stained nuclei. Results were analyzed with Student’s t-test. In our study, the female to male ratio was 8.3:1. The median age of patients was 50 years ; 35.5% of patients were younger than 45. Tumor multifocality was found in 27.4% of patients. LN metastases were found in nine patients. Younger age (p=0.046) and male sex (p<0.001) were strong predictors of LN metastases. Cyclin D1 was expressed in 44.6% of PMC. p27 was expressed in 83.1% of cases. Cyclin D1 inversely correlated with p27 (p=0.049). Overexpression of cyclin D1 did not correlate with any clinical or histopathologic parameter. Underexpression of p27 had an influence on tumor multifocality (p=0.023) and tendency to correlate with LN metastases (p=0.073). Expressions of cyclin D1 and p27 cannot be used as markers of high risk PMC although our results indicated that the cell cycle regulation was disrupted.

cyclin D1 ; p27 ; papillary microcarcinoma ; thyroid gland

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