Cytoplasmic Localization of Jab1 and p27^Kip1 Might Be Associated with Invasiveness of Papillary Thyroid Carcinoma

Abstract

p27^kip1 is a well known negative regulator of cell cycle progression. Jab1 directly binds to p27^kip1 and induces nuclear export and subsequent degradation. Recent studies have shown that overexpression of Jab1 and reduced expression of p27^kip1 are associated with advanced tumor stage and poor prognosis in several human cancers. Here, we evaluated 50 papillary thyroid carcinomas (PTC) and adjacent normal thyroid tissue samples by immunohistochemistry for Jab1 and p27^kip1 to elucidate expression levels and subcellular localization. Expression of Jab1 was markedly increased and that of p27^kip1 was reduced in the tumors compared with paired normal samples. Jab1 expression was inversely related to p27^kip1 expression. Jab1 was especially overexpressed within the invasive region compared to center of the tumors. Among clinicopathologic parameters, only tumor size was related with Jab1 (positively) and p27^kip1 expression (negatively) in the invasive region of the tumors. Both Jab1 and p27^kip1 were found predominantly in the cytoplasm of the tumor cells from the invasive regions compared to center of the tumors. The Ki-67 proliferative index was higher in the invasive region than in center of the tumors. A much stronger correlation with the Ki-67 index was noted when both Jab1 and p27^kip1 were simultaneously localized in the cytoplasm than when either Jab1 or p27^kip1 was localized in the cytoplasm alone. These data suggest that in addition to overexpression of Jab1 and reduced expression of p27^kip1, cytoplasmic localization of Jab1 and p27^kip1 are associated with increased cancer cell proliferation and might be related to the invasiveness of PTC.