The Use of p16 in Enhancing the Histologic Classification of Uterine Smooth Muscle Tumors

Abstract

Uterine smooth muscle tumors can usually be divided histologically into leiomyoma (L) and leiomyosarcoma (LMS). Occasionally, the histologic features are indeterminate and classified as smooth muscle tumor of uncertain malignant potential (STUMP). Recent gene expression studies have found p16 overexpressed in LMS when compared with normal myometrium. This study evaluated the protein expression of p16 by immunohistochemistry in LMS, L, and normal myometrium. Additionally, 8 tumors originally classified as STUMP were evaluated for p16 expression and correlated to their clinical outcome. A tissue microarray was constructed and composed of 15 LMS, 8 STUMPs, 22 L, and 10 samples of normal myometrium. p16 expression was correlated with clinical outcome and histologic features. Twelve of the 15 LMS strongly and diffusely expressed p16, 3 of the L had focal p16 staining, and none of the normal myometria were p16 positive. Three of the tumors originally classified as STUMP developed metastatic disease and 2 of these tumors had strong, diffuse p16 positivity. Histologically, these 2 cases were characterized by coagulative tumor cell necrosis and only mild cytologic atypia. p16 is preferentially expressed in LMS with only rare L showing positivity. Histologically, tumors with coagulative tumor cell necrosis alone were clinically LMS. In those cases in which the type of necrosis is uncertain (coagulative tumor cell vs. hyalinized), the addition of p16 may aid in discerning a subset of STUMP that should be classified as LMS.