Comparative clinicopathologic and immunohistochemical analysis of uterine sarcomas diagnosed using the World Health Organization classification system

Abstract

Uterine sarcomas are rare tumors that account for 3% to 7% of uterine cancers. Their histopathologic classification was revised by the World Health Organization (WHO) in 2003. The objectives of this study were to determine the frequency of different subtypes of uterine sarcoma applying the WHO criteria to a series of cases, compare the outcome of patients with different subtypes, and compare their immunoprofiles using a panel of immunomarkers. Thirty-four uterine sarcomas were identified for a 20-year period (1988-2008). Eighteen benign tumors of smooth muscle or endometrial stromal origin served as a comparison group. A tissue microarray was prepared and immunostaining performed for 10 selected oncoproteins involved in cell proliferation (Ki-67, P53, p16, and phosphatase and tensin homolog [PTEN]), cell differentiation (CD10, h-caldesmon, estrogen receptor, and progesterone receptor), and apoptosis (bcl-2 and Twist). Hierarchical clustering analysis of the immunohistochemical results was performed. The uterine sarcomas were classified as follows: 20 leiomyosarcomas, 9 endometrial stromal sarcomas, and 5 undifferentiated endometrial sarcomas. The outcome for patients with uterine sarcoma was poor, irrespective of histologic type, even for those with stage I tumors. Of the patients with follow-up available, 12 (67%) of 18 with leiomyosarcoma, 4 of 5 with undifferentiated sarcoma, and 4 of 7 with endometrial stromal sarcoma experienced recurrence and 8 patients with high-grade sarcomas died of tumor. In our series, most uterine sarcomas were leiomyosarcomas. Comparison was made between leiomyosarcomas that recurred and those with a favorable outcome and 3 patients with leiomyosarcoma without evidence of recurrence on long-term follow-up had tumors that were negative/low expressors of Ki-67, p53, p16, and Twist, with strong expression of bcl-2. A subset of undifferentiated endometrial sarcomas composed of cells with uniform nuclei may be a separate entity from those with nuclear anaplasia and may be related to low-grade endometrial stromal sarcomas. It may be possible to identify a subset of leiomyosarcomas with a favorable prognosis based on staining with a panel of immunomarkers for cell proliferation and apoptosis.