Tumor protein p53-induced nuclear protein (TP53INP1) expression in medullary thyroid carcinoma: a molecular guide to the optimal extent of surgery?

Abstract

Background: Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent.

Methods: Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears.

Results: TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts.

Conclusions: TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.