Endometrial sarcomas: an immunohistochemical and JAZF1 re-arrangement study in low-grade and undifferentiated tumors.
The current World Health Organization classification divides endometrial sarcomas into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma. Recent studies suggest undifferentiated endometrial sarcoma is a heterogeneous group and a subgroup with uniform nuclei is more akin to low-grade endometrial stromal sarcoma in terms of morphologic, immunohistochemical and genetic features. We classified endometrial sarcomas treated at our institution from 1998 to 2011 into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma, the latter being further categorized into a group with either uniform or pleomorphic nuclei. Morphological features, immunoprofile and fluorescence in situ hybridization rearrangements of JAZF1 and PHF1 genes were correlated with tumor category and outcome. A total of 40 cases were evaluated comprising 23 low-grade endometrial stromal sarcomas, 10 undifferentiated endometrial sarcomas with nuclear uniformity and 7 undifferentiated endometrial sarcomas with nuclear pleomorphism. Low-grade endometrial stromal sarcomas were more often estrogen and progesterone receptor positive (83%) compared with undifferentiated endometrial sarcoma with nuclear uniformity (10%) or with nuclear pleomorphism (0%) (P<0.001). Positivity for p53 was restricted to undifferentiated endometrial sarcomas with more frequent expression in the group with nuclear pleomorphism (57%) than with nuclear uniformity (10%) (P=0.06). Ki-67 proliferation index in >10% of tumor cells more frequent in undifferentiated endometrial sarcoma than low-grade endometrial stromal sarcoma (P=<0.001). JAZF1 rearrangement was detected in 32% of low-grade endometrial stromal sarcomas and in none of the undifferentiated sarcomas. Rearrangement of PHF1 was found in two patients, one with JAZF1-PHF1 fusion. There were no significant differences in clinical behavior between undifferentiated endometrial sarcoma with nuclear uniformity versus nuclear pleomorphism. In conclusion, we found undifferentiated endometrial sarcoma subtypes and low-grade endometrial stromal sarcoma have distinct immunohistochemical and cytogentic profiles. Our data do not show any difference in clinical behavior between subgroups in undifferentiated sarcomas.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Kiran
K
Jakate
Farshad
F
Azimi
Rola H
RH
Ali
Cheng-Han
CH
Lee
Blaise A
BA
Clarke
Golnar
G
Rasty
Patricia A
PA
Shaw
Nataliya
N
Melnyk
David G
DG
Huntsman
Stephane
S
Laframboise
Marjan
M
Rouzbahman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D063146:Polycomb-Group Proteins; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics
D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C430460:JAZF1 protein, human; D009363:Neoplasm Proteins; C112309:PHF1 protein, human; D063146:Polycomb-Group Proteins; D014157:Transcription Factors