Expression of p16 protein in patients with uterine smooth muscle tumors: an immunohistochemical analysis

Abstract

Objective The loss of cell cycle control is a critical step in the development of neoplasia. The p16 protein has been identified as a tumor suppressor protein, which binds specifically to the cyclin-dependent kinase CDK-4, inhibiting the catalytic activity of the CDK4-cyclin D complex, and thereby acts as a negative cell cycle regulator. In the present study, we compared the expression of p16 protein in cases with leiomyoma, uterine smooth muscle tumor of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). Methods P16 expression was investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. Results P16 was expressed in 12% of leiomyomas, in 21% of STUMP, and in 57% of LMS. A statistically significant difference regarding the frequency of p16 protein expression was observed between LMS and STUMP ( P < 0.05) as well as between LMS and leiomyoma ( P < 0.05), but not between STUMP and leiomyoma ( P > 0.05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma and between LMS and STUMP ( P < 0.05), but no statistical significant difference was observed between STUMP and leiomyoma ( P > 0.05). No statistically significant correlation between p16 expression and clinical stage, age, vascular space involvement, and recurrence disease could be found in patients with LMS ( P > 0.05). Additionally, the overall survival did not significantly differ between p16-positive and p16-negative cases ( P > 0.05). Conclusions We found that p16 was more frequently and more strongly expressed in LMS compared to STUMP and leiomyoma. We therefore concluded that p16 might play an important role in sarcomagenesis. Furthermore, p16 might be a useful immunohistochemical marker, which could help to distinguish cases of smooth muscle tumors in which histologic features are ambiguous or borderline, but the use of p16 in a diagnostic setting should await further clinical studies and clarification of the mechanisms.