title: Endometrial stromal sarcomas with sex cord differentiation are associated with PHF1 rearrangement.
abstract: Endometrial stromal tumors may pose diagnostic challenges particularly when they exhibit variant histologic appearances, involve extrauterine sites, or present as metastatic disease. In such cases, use of immunohistochemical markers and identification of specific nonrandom chromosomal rearrangements may be helpful. Over the last decade, fluorescence in situ hybridization (FISH) has been progressively incorporated as a diagnostic tool for the evaluation of endometrial stromal tumors. The purpose of this study was to review a series of these tumors and compare the results of FISH analysis with the clinicopathologic characteristics. Three endometrial stromal nodules (ESNs), 13 endometrial stromal sarcomas (ESSs), and 7 undifferentiated endometrial sarcomas (UESs) were reviewed. Three metastases from 1 of the ESS cases were also analyzed. Nine of these tumors (1 ESN, 8 ESSs, and 1 UES) exhibited unusual histologic features, including smooth muscle (3), sex cord (7), epithelioid (1), fibromyxoid (1), and skeletal muscle (2) differentiation. A tissue microarray was prepared, and FISH analysis was performed using break-apart and fusion probes for JAZF1, SUZ12, EPC1, and PHF1 genes. FISH was successful in 22 cases, and rearrangements involving JAZF1, SUZ12, EPC1, and PHF1 genes were detected in 10 of the 22 (45%) uterine tumors, including 2 of the 3 ESNs and 8 of 12 ESSs. Genetic rearrangements were found neither in the 3 metastases of the ESS nor in any of the UESs. It is noteworthy that a correlation between sex cord differentiation and PHF1 rearrangement was encountered in ESSs (P=0.008). In our series, all ESSs showing sex cords had PHF1 genetic rearrangement, suggesting that such rearrangements may induce sex cord differentiation.
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau, Institut of Biomedical Research (IIB Sant Pau), Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Emanuela
authors.initials: E
authors.lastname: D'Angelo
authors.forename: Rola H
authors.initials: RH
authors.lastname: Ali
authors.forename: Inigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: Blake
authors.initials: B
authors.lastname: Gilks
authors.forename: Jaime
authors.initials: J
authors.lastname: Prat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D063146:Polycomb-Group Proteins; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D018312:Sex Cord-Gonadal Stromal Tumors / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C112309:PHF1 protein, human; D063146:Polycomb-Group Proteins; D014157:Transcription Factors