Diagnostic use of nuclear Β-catenin expression for the assessment of endometrial stromal tumors

Abstract

Alterations in Β-catenin degradation cause it to accumulate to immunohistochemically detectable levels in the nuclei of tumor cells. Although it has been shown that nuclear Β-catenin immunostaining is useful for the diagnosis of some mesenchymal tumors, there is little known about Β-catenin expression in endometrial stromal tumors. In this study, nuclear Β-catenin immunoreactivity was evaluated in normal endometrium and endometrial mesenchymal tumors and then compared with that of CD10. The endometrial mesenchymal tumors evaluated included endometrial stromal nodules (n=2), low-grade endometrial stromal sarcomas (n=12), undifferentiated endometrial sarcomas (n=8) and uterine cellular leiomyomata (n=9). In addition, direct DNA sequencing of Β-catenin exon 3 was conducted in 15 endometrial stromal tumors. Normal endometrial stromal cells showed strong cytoplasmic reactivity for CD10 but no detectable reactivity for Β-catenin. Nuclear Β-catenin immunoreactivity was detected in 11 low-grade endometrial stromal sarcomas (92%) and 6 undifferentiated endometrial sarcomas (75%). Ten low-grade endometrial stromal sarcomas (83%) and six undifferentiated endometrial sarcomas (75%) were positive for CD10. Eight low-grade endometrial stromal sarcomas (67%) exhibited diffuse, strong nuclear immunoreactivity with Β-catenin, whereas only four cases (33%) expressed diffuse, strong immunoreactivity with CD10. All nine cases of uterine cellular leiomyomata were completely negative for both CD10 and Β-catenin. Β-catenin mutations were rare in endometrial stromal tumors. Taken together, these results indicate that nuclear Β-catenin immunostaining can serve as a sensitive immunohistochemical marker for the diagnosis of endometrial stromal tumors and is useful for differentiating low-grade endometrial stromal sarcomas from uterine cellular leiomyomata.