Clinicopathological and Immunohistochemical Study in 148 Uterine Sarcomas: Bcl-2 and Proliferative Markers Identify Different Prognostic Groups of Uterine Leiomyosarcomas
E D'Angelo, R Ali, I Espinosa, CB Gilks, M Van de Rijn, C-G Lee, J Prat. Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain; University of British Columbia, Vancouver, BC, Canada; Stanford University Medical Center, Stanford, CA
Background: Other than stage, the prognostic parameters of uterine sarcomas are ill defined. Previously, we suggested that uterine leiomyosarcomas with strong bcl-2 immunoreaction and weak expression of proliferative markers are associated with good prognosis.
Design: To confirm this assumption, we studied the expression of bcl-2, Ki-67, TP53, and P16 in 148 uterine sarcomas (105 leiomyosarcomas, 32 endometrial stromal sarcomas, and 11 undifferentiated endometrial sarcomas) distributed over 3 TMAs.
Results: In leiomyosarcomas, strong bcl-2 staining was associated with good prognosis (P=0.009) whereas cases with high expression of Ki-67, TP53, and P16 had adverse prognosis (P=0.01, P=0.02, and P=0.03, respectively). Using the four markers, unsupervised hierarchical clustering analysis identified 3 groups with significant differences in survival (P=0.004). Leiomyosarcomas with strong bcl-2 expression were associated with good prognosis regardless of their immunoreactivity for P16 (groups 1 and 3), whereas the leiomyosarcomas lacking bcl-2 that reacted for P16 had worse prognosis (group 2). In a multivariate analysis, these cluster groups were of prognostic significance independent of age, tumor size, necrosis, mitosis, and nuclear atypia (hazard ratio, 3; 95% CI, 1.2 to 7.2; P=0.01). Almost all endometrial stromal sarcomas (28/32; 90%) clustered in the group with favorable prognosis (group 1). In contrast, most undifferentiated endometrial sarcomas (10/11; 91%) clustered in the group with poor prognosis (group 2).
Conclusions: Prognostically, leiomyosarcomas can be separated in different groups according to their expression of bcl-2 and P16 both of which may play a role in their pathogenesis. The distribution of endometrial stromal sarcomas and undifferentiated endometrial sarcomas paralleled that of leiomyosarcomas with favorable and unfavorable prognosis respectively.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 9:00 AM
Platform Session: Section D, Monday Morning