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

• Published in: International journal of cancer Vol. 136; no. 7; pp. 1608 - 1618
• Main Authors: Gremel, Gabriela, Liew, Markus, Hamzei, Farzaneh, Hardell, Elin, Selling, Jonas, Ghaderi, Mehran, Stemme, Sten, Pontén, Fredrik, Carlson, Joseph W.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2015
• Subjects: 14-3-3 Proteins - genetics; Adult; Aged; Biology; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; endometrial stromal sarcoma; Female; Follow-Up Studies; Humans; Medical prognosis; Medical research; Medicin och hälsovetenskap; Middle Aged; Mitotic Index; Neoplasm Grading; Neoplasm Staging; Prognosis; Sarcoma - diagnosis; Sarcoma - genetics; Sarcoma - metabolism; Sarcoma - mortality; Translocation, Genetic; Tumors; undifferentiated uterine sarcoma; Uterine cancer; Uterine Neoplasms - diagnosis; Uterine Neoplasms - genetics; Uterine Neoplasms - metabolism; Uterine Neoplasms - mortality; endometrial stromal sarcoma; undifferentiated uterine sarcoma; prognosis; biomarkers
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.29141

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. What's New? Undifferentiated uterine sarcomas are rare tumors with a heterogeneous biology and an overall poor prognosis. While attempting to subdivide them based on prognosis has been difficult, it may provide insights into their biology. This work is the first to examine the effect of clinical, pathological, biomarker and molecular changes on patient survival. It demonstrates that the tumors can be subdivided into prognostic groups using mitotic index, hormone receptor expression, and YWHAE‐FAM22 translocation status, and that a group exists that may benefit from hormone therapy. This work provides survival‐analysis driven recommendations for tumor sub‐classification as well as possible insights for treatment.