Immunohistochemical and Molecular Characterization of Endometrial Stromal Sarcomas

Abstract

Introduction: Endometrial stromal sarcomas (ESSs) are rare and characterized by translocations t(7;17)(p15;q11.2) and t(10;17)(q22;p13), resulting in JAZF1-SUZ12 and YWHAE-FAM22 gene fusions used for defining low-grade (LG-ESS) and high-grade (HG-ESS) tumours. Aim: The objective of the study was to characterize ESSs using immunohistochemical and molecular markers. Material and Methods: Patients diagnosed as having ESSs between January 2014 and December 2018 were included in the study. The slides were reviewed along with a panel of immunohistochemical markers, CD10, cyclin D1, oestrogen receptor (ER) and progesterone receptor (PR), Ki67, and vimentin and classified according to World Health Organization (2014) criteria into LG-ESS, HG-ESS, and undifferentiated uterine sarcoma (UUS). Molecular characterization was performed by fluorescence in situ hybridization using relevant probes. Results: Over a 4-year period, 552 cases of endometrial malignancies were reported, 10 of which were ESS (1.8%). Of these, 5 were LG-ESS, 3 HG-ESS, and 2 UUS. CD10 was 100% sensitive and 75% specific for LG-ESS. Oestrogen receptor and PR were 100% specific but less sensitive (80%) for LG-ESS. Forty per cent (2/5) of LG-ESS demonstrated JAZF1-SUZ12 gene rearrangement. All 3 cases of HG-ESS showed diffuse strong cyclin D1 (>70% nuclei) positivity and were negative for cluster differentiation 10, ER, and PR and demonstrated YWHAE gene rearrangement. None of the UUS cases demonstrated this gene rearrangement. Conclusion: Endometrial stromal sarcomas are rare tumours (1.8% in this study). JAZF1-SUZ12 and YWHAE-FAM22 gene rearrangement helps in accurate characterization of ESS and can be used as diagnostic tools especially when the diagnosis is unclear or difficult. Cyclin D1 can be used as an adjuvant immunomarker for YWHAE gene–rearranged HG-ESS.

Interrogating the Genomic Landscape of Uterine Leiomyosarcoma: A Potential for Patient Benefit

“…Low-grade endometrial stromal sarcomas (LGESS) may show some positivity for smooth muscle markers and will also show diffuse positivity for CD10, ER, and PR, making them very difficult to differentiate from uLMS [30]. HGESS, however, show positivity for Cyclin-D1 and BCOR and will lack expression of CD10, ER, and PR [31]. HGESS also harbour YWHAE::NUTM2A/B gene fusions and BCOR rearrangements, which are diagnostic and not associated with uLMS [32], whilst the gene fusion JAZF1::SUZ12 is most common in LGESS [33].…”

Update on Endometrial Stromal Tumours of the Uterus

“…CD10 antibody is routinely used for the diagnosis of ESTs, ( Figure 3 A) and is the most popular antibody used to differentiate LG-ESS from HG-ESSs [ 54 , 55 , 56 , 57 , 58 ]. However, it is well known that CD10 is not specific for the diagnosis of ESTs [ 59 , 60 ] and some ESTs may show negative immunostaining with CD10 [ 61 , 62 ].…”

“…LG-ESSs demonstrate strong expression with ERα ( Figure 3 B) [ 54 , 56 , 57 , 58 , 61 , 64 , 65 , 66 , 67 , 68 ], while ER-beta (ERβ) expression is mainly negative with occasional reported cases showing weak positivity [ 64 ]. PR expression positivity has been reported in the majority of cases (>70%), with strong positivity observed in >50% of cases [ 58 , 64 , 69 , 70 ] and its positivity is part of the immunohistochemical confirmation of the diagnosis of LG-ESS [ 54 , 56 , 61 , 65 , 66 , 67 ].…”

“…The round cell component is positive for Cyclin D1 ( Figure 7 B), BCOR, CD117 (c-kit), CD56, and CD99, whereas DOG1 is negative [ 7 , 57 , 63 , 77 , 95 , 96 ]. Generally, ER and PR are negative, but positive staining has also been reported; CD10 shows variable expression, either positive or negative [ 7 , 56 , 97 ].…”

“…These neoplasms demonstrate rearrangement of YWHAE ( Figure 8 ) and commonly harbour YWHAE-NUTM2 fusion [ 5 , 7 , 57 ]. NUTM2 has been previously named as FAM22 by HUGO Gene Nomenclature Committee (HGNC) Symbols [ 98 ].…”