Increased expression of transketolase-like-1 in papillary thyroid carcinomas smaller than 1.5 cm in diameter is associated with lymph-node metastases.

BACKGROUND: Patients with small papillary thyroid carcinoma (PTC) may have a high incidence of regional lymph-node (LN) metastases at presentation, and these are considered to be an independent risk factor for tumor recurrence. A mutated transketolase transcript (TKTL1) has been found up-regulated in different human malignancies, and strong TKTL1 protein expression has been associated with aggressiveness and poor patient survival in several epithelial cancers. METHODS: TKTL1 protein expression was analyzed in 256 consecutive cases of PTCs <or=1.5 cm by immunohistochemistry with a specific anti-TKTL1 antibody. RNA analysis was performed by real-time polymerase chain reaction (PCR) in all cases for which frozen material was available, which resulted in 55 fragments of PTC. RESULTS: Increased levels of TKTL1 transcript were detected in 50 of 55 analyzed tumors compared with their corresponding normal tissues. Significant differences in TKTL1 transcript levels were found between cases of PTC with and without LN metastases. In primary tumors, immunoreactivity for TKTL1 was detected in the majority of cases, ranging from 0% to 95.0% (mean, 50.11% +/- 27.75%). A significant association was found between TKTL1 protein expression and the presence of multifocality, bilaterality, extrathyroidal extension, vascular invasion, sclerosis, and LN metastases. In cases with LN metastases, a positive correlation was found between the TKTL1 protein expression in primary tumors and the number of metastatic LNs as well as the diameter of the largest metastatic area in LNs. CONCLUSIONS: These findings suggest that TKTL1 overexpression in PTC <or=1.5 cm may be considered a factor that facilitates tumor growth and progression. (c) 2008 American Cancer Society.