Molecular biomarkers for uterine leiomyosarcoma and endometrial stromal sarcoma

Abstract

Uterine leiomyosarcoma (u‐LMS) and endometrial stromal sarcoma (ESS) are among the most frequent soft tissue sarcomas, which, in adults, lead to fatal lung metastases and patients have an extremely poor prognosis. Due to their rarity and heterogeneity, there are no suitable biomarkers for diagnosis and prognosis, although some biomarker candidates have appeared. In 2017, The Cancer Genome Atlas (TCGA) Research Network's work on u‐LMS has confirmed mutations and deletions in RB1,TP53 and PTEN. In addition, whole‐exome sequencing of u‐LMS has confirmed and demonstrated frequent alterations in TP53,RB1, α‐thalassemia/mental retardation syndrome X‐linked (ATRX) and mediator complex subunit 12 (MED12). MED12 is a useful biomarker to diagnose uterine‐derived LMS and tumors arising from (LM) with a relatively favorable prognosis. TP53 and ATRX mutations can be important mechanisms in the pathogenesis of u‐LMS and are correlated with a poor prognosis. In an update based on the 2014 WHO classification, low‐grade ESS is often associated with gene rearrangement bringing about the JAZF 1‐SUZ12 (formerly JAZF1‐JJAZ1) fusion gene, whereas high‐grade ESS is associated with the YWHAE‐NUTM fusion gene. Low‐grade ESS with JAZF1 rearrangement may correlate with metastasis. However, high‐grade ESS with metastasis with YWHAE rearrangement shows a relatively favorable prognosis. The genetic/molecular genetic aberrations in u‐LMS and ESS are reviewed, focusing on molecular biomarkers for these primary and metastatic tumors.

Could miRNA Signatures be Useful for Predicting Uterine Sarcoma and Carcinosarcoma Prognosis and Treatment?

“…To the best of our knowledge, there are no adequate biomarkers available yet for the diagnosis or correct evaluation of these neoplasms. miRNAs have been studied in uterine tumors, and aberrant expression patterns were identified in several sarcoma types [ 25 ]. Clinical features such as age, stage, tumor size, presence or absence of necrosis, and mitotic index [ 6 ] along with miRNA differential expression profiles might be important to determining these tumors’ prognoses.…”

Cancer Is Associated with Alterations in the Three-Dimensional Organization of the Genome

“…The TAD-based models for sarcoma (SARC), which achieved a median c-index of 0.58, is a notable case. SARC patients usually harbor a relatively large number of variants in non-coding regions and no very good gene markers are known [29][30][31]. Indeed, our gene-based models were unable to reliably predict survival (median c-index = 0.52).…”

A Case of Endometrial Stromal Sarcoma Revealed by Lung Metastasis 7 Years after Hysterectomy which Led to Histological Diagnosis of Uterine Fibroid

“…ESS is a rare tumour, accounting for between 0.2% and 1% of all malignant tumours of the uterus. Diagnosis is based on morphological and immunohistochemical or even molecular biology criteria [9]. Our patient had experienced a total hysterectomy with bilateral annexectomy in 2010, the histology of the operating material had not concluded malignancy, but it had not been completed by an immunohistochemical study; we cannot therefore a posteriori eliminate a false anatomopathological diagnosis.…”