A prognosis based classification of undifferentiated uterine sarcomas: Identification of mitotic index, hormone receptors and YWHAE‐FAM22 translocation status as predictors of survival

Abstract

Undifferentiated uterine sarcomas (UUS) are rare tumors with a heterologous biology and a poor prognosis. The goal of this study was to examine clinicopathology, biomarkers and YWHAE-FAM22 translocation status, in the prognosis of these tumors. Twenty-six cases of UUS were included. All original slides were rereviewed and age at diagnosis, tumor stage, "Kurihara" diagnosis, mitotic index, presence of necrosis and grade of nuclear atypia were recorded. Additionally, a tissue microarray was constructed from 22 of the cases, and the protein biomarkers P53, P16, Ki-67, Cyclin-D1, ER, PR and ANLN were evaluated by immunohistochemistry. All tumors were evaluated for the presence of a YWHAE-FAM translocation; the translocation was demonstrated in the three Cyclin-D1 positive tumors. Follow-up data in the form of overall survival were available on all patients. These tumors could be divided into two prognostic groups, a high mitotic index group (10 cases, M 5 36.8, SD 5 5.4) and a low mitotic index group (16 cases, M 5 8.7, SD 5 5.8). These two groups showed a statistically significant difference in prognosis. The expression of ER, PR or presence of the YWHAE-FAM22 translocation correlated with low mitotic index and an additionally improved prognosis, although the number of cases was small. These results indicate that UUS can be divided into two prognostic groups using mitotic index as a primary criteria, followed by expression of either ER, PR or the presence of a YWHAE-FAM22 translocation as a secondary criteria. This study demonstrates the presence of statistically significant prognostic subgroups within UUS, and provides treatment insights.

Endometrial stromal tumours revisited: an update based on the 2014 WHO classification

“…Additionally, separating HGESS from LGESS is as important since they appear to be more aggressive clinically with frequent extrauterine disease at initial presentation 66 67. Based on the limited data available, the prognosis of YWHAE -rearranged cases seems to be intermediate between that of LGESS and UUS 66 68. These tumours usually present as abnormal vaginal bleeding similar to LGESS.…”

Practical issues related to uterine pathology: endometrial stromal tumors

“…Histologically, UUS has been subdivided into two histologic appearances-uniform (UUS-u) and pleomorphic (UUS-p) by Kurihara et al 54 It is important to note that, as described, UUS-u not only shows morphologic and immunophenotypic overlap with high-grade ESS, but also most tumors classified as such have subsequently been shown to harbor t (10;17) and thus for purposes of classification, many but not all, are now recognized as high-grade ESS. 55 UUS-p typically shows destructive myometrial infiltration, a fascicular or patternless growth pattern and is composed of highly pleomorphic cells with no resemblance to proliferative phase endometrial stroma. These tumors are typically CD10, p53, and cyclin D1 positive (which can be diffuse), but are usually negative for ER and PR.…”

ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity

“…2,4,7,10 Overall, clinical outcomes appear intermediate between low-grade endometrial stromal sarcoma and undifferentiated uterine sarcoma. 4,11 Although YWHAE-NUTM2 high-grade endometrial stromal sarcoma is now readily recognizable by its characteristic morphologic features, other types of high-grade endometrial stromal sarcomas with alternative gene fusions likely exist and may currently be misclassified as undifferentiated uterine sarcoma or leiomyosarcoma. 7,12 ZC3H7B-BCOR gene fusion resulting from the chromosomal translocation t(X;22)(p11;q13) was recently identified in both ossifying fibromyxoid tumors 13 and endometrial stromal sarcomas, 14 the latter in which tumor grade was not specified.…”