title: 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 = 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.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, S-751 85, Uppsala, Sweden; Science for Life Laboratory, Uppsala University, S-751 85, Uppsala, Sweden.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gremel
authors.forename: Markus
authors.initials: M
authors.lastname: Liew
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Hamzei
authors.forename: Elin
authors.initials: E
authors.lastname: Hardell
authors.forename: Jonas
authors.initials: J
authors.lastname: Selling
authors.forename: Mehran
authors.initials: M
authors.lastname: Ghaderi
authors.forename: Sten
authors.initials: S
authors.lastname: Stemme
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Carlson
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012509:Sarcoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D014178:Translocation, Genetic; D014594:Uterine Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; C482983:YWHAE protein, human
keywords: biomarkers; endometrial stromal sarcoma; prognosis; undifferentiated uterine sarcoma