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

Alterations in beta-catenin degradation cause it to accumulate to immunohistochemically detectable levels in the nuclei of tumor cells. Although it has been shown that nuclear beta-catenin immunostaining is useful for the diagnosis of some mesenchymal tumors, there is little known about beta-catenin expression in endometrial stromal tumors. In this study, nuclear beta-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 beta-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 beta-catenin. Nuclear beta-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 beta-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 beta-catenin. beta-catenin mutations were rare in endometrial stromal tumors. Taken together, these results indicate that nuclear beta-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.