Gremel Gabriela, Liew Markus, Hamzei Farzaneh, Hardell Elin, Selling Jonas, Ghaderi Mehran, Stemme Sten, Pontén Fredrik, Carlson Joseph W
Department of Immunology, Genetics and Pathology, Uppsala University, S-751 85, Uppsala, Sweden; Science for Life Laboratory, Uppsala University, S-751 85, Uppsala, Sweden.
Int J Cancer. 2015 Apr 1;136(7):1608-18. doi: 10.1002/ijc.29141. Epub 2014 Aug 27.
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 = 36.8, SD = 5.4) and a low mitotic index group (16 cases, M = 8.7, SD = 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.
未分化子宫肉瘤（UUS）是一种生物学行为异质性且预后较差的罕见肿瘤。本研究的目的是探讨这些肿瘤预后中的临床病理学、生物标志物及YWHAE-FAM22易位状态。纳入了26例UUS病例。重新复查所有原始切片，并记录诊断时的年龄、肿瘤分期、“栗原”诊断、有丝分裂指数、坏死情况及核异型性分级。此外，从22例病例中构建了组织芯片，并通过免疫组织化学评估蛋白质生物标志物P53、P16、Ki-67、细胞周期蛋白D1、雌激素受体（ER）、孕激素受体（PR）和锚蛋白（ANLN）。评估所有肿瘤中YWHAE-FAM易位的存在情况；在3例细胞周期蛋白D1阳性肿瘤中证实了易位。所有患者均有以总生存形式的随访数据。这些肿瘤可分为两个预后组，高有丝分裂指数组（10例，M = 36.8，标准差 = 5.4）和低有丝分裂指数组（16例，M = 8.7，标准差 = 5.8）。这两组在预后方面显示出统计学上的显著差异。ER、PR的表达或YWHAE-FAM22易位的存在与低有丝分裂指数及预后改善相关，尽管病例数较少。这些结果表明，UUS可使用有丝分裂指数作为主要标准分为两个预后组，其次以ER、PR的表达或YWHAE-FAM22易位的存在作为次要标准。本研究证明了UUS中存在具有统计学意义的预后亚组，并提供了治疗方面的见解。
