Detection of MEAF6‐PHF1 translocation in an endometrial stromal nodule

Abstract

Endometrial stromal nodule (ESN) and low-grade endometrial stromal sarcoma (LG-ESS) are rare uterine tumors known as endometrial stromal tumors (ESTs). In addition to their similarity in morphological features, recent studies have shown that these two tumors share common genetic alterations. In particular, JAZF1-SUZ12 fusion is found with high frequency in both ESN and LG-ESS. In LG-ESS, some minor fusions have also been described, which include rearrangements involving PHF1 and its partner genes, such as JAZF1, EPC1, MEAF6, BRD8, EPC2, and MBTD1. Because of the rarity of ESN, genetic alterations other than JAZF1 fusion have not been investigated in detail. In this study, we performed a next-generation sequencing-based analysis in a case of ESN with peripheral metaplastic bone formation and detected MEAF6-PHF1 fusion, which has been reported in a small subset of uterine LG-ESSs and soft tissue ossifying fibromyxoid tumors. The finding that MEAF6-PHF1 fusion is a background genetic abnormality detected both in ESN and LG-ESS, along with JAZF1-SUZ12, provides further support for the similarity and continuum between these two types of ESTs. Furthermore, the association between metaplastic bone formation and MEAF6-PHF1 fusion may not be limited to soft tissue tumors.

Molecular pathogenesis and prognostication of "low‐grade'' and "high‐grade" endometrial stromal sarcoma

“…This chimera has been found more frequently in classic LG‐ESS than in LG‐ESS exhibiting variant features 28 . Recently, an ESN with MEAF6/PHF1 was reported, providing further support for a continuum between these two tumor entities 29 . Interestingly, the ESN showed focal peripheral ossification, a rare feature of ESN and/or LG‐ESS but a hallmark of ossifying fibromyxoid tumors with which they may share also other molecular events such as PHF1 fusions, that is, EP400/PHF1 , MEAF6/PHF1 , and EPC1/PHF1 .…”

Targeted RNA Sequencing Highlights a Diverse Genomic and Morphologic Landscape in Low-grade Endometrial Stromal Sarcoma, Including Novel Fusion Genes

“…The first had a morphology and immunophenotype in keeping with LGESS and was found to harbor a MEAF6::PTGR2 fusion. MEAF6 (MYST/Esa1 Associated Factor 6), which was previously reported as a fusion partner with PHF1 and SUZ12 in ESN 50 and…”

“…The first had a morphology and immunophenotype in keeping with LGESS and was found to harbor a MEAF6::PTGR2 fusion. MEAF6 (MYST/Esa1 Associated Factor 6), which was previously reported as a fusion partner with PHF1 and SUZ12 in ESN 50 and LGESS, 45,51 is a component of the H4 histone acetyltransferase complex 52,53 . PTGR2 encodes prostaglandin reductase 2, an enzyme involved in prostaglandin metabolism, 54 which is expressed in both normal endometrium 55 and endometrial carcinoma 56 .…”

Update on Endometrial Stromal Tumours of the Uterus

“…p53 demonstrates a wild-type pattern of expression. The mitotic rate, evaluated by Ki67 expression, is low [ 53 ].…”

“…The data on expression of cytokeratins are conflictual. Positive immunoreactivity to AE1/3 and CAM5.2 has been reported [ 52 , 53 ], but negative cases have also been described [ 67 , 73 ].…”