Androgen receptor as a prognostic biomarker and therapeutic target in uterine leiomyosarcoma

Baek, Min-Hyun; Park, Yangsoon; Kim, Kyu Rae; Kim, Dae Yeon; Kim, Jong Hyeok; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun

doi:10.3802/jgo.2018.29.e30

Cited by 15 publications

(10 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The uLMS subtype maintains components of a myometriumderived gene-expression program, including expression of estrogen, progesterone, and prolactin receptors. There is limited evidence that targeting the estrogen receptor with aromatase inhibition may have clinical benefit in select ULMS patients (58), suggesting functional dependency upon myometrial lineage-related hormonal receptors (59). Whether the ectopic expression of prolactin in a subset of uLMS supports tumor growth in an autocrine loop is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic Gene-Expression Programs in Leiomyosarcoma and Characterization of Conventional, Inflammatory, and Uterogenic Subtypes

Hemming

Fan

Raut

et al. 2020

Molecular Cancer Research

View full text Add to dashboard Cite

◥Leiomyosarcoma (LMS) is a mesenchymal neoplasm with complex copy-number alterations and characteristic loss of tumor suppressor genes without known recurrent activating mutations. Clinical management of advanced LMS relies on chemotherapy and complementary palliative approaches, and research efforts to date have had limited success identifying clinically actionable biomarkers or targeted therapeutic vulnerabilities. To explore the biological underpinning of LMS, we evaluated gene-expression patterns of this disease in comparison with diverse sarcomas, nonmesenchymal neoplasms, and normal myogenic tissues. We identified a recurrent gene-expression program in LMS, with evidence of oncogenic evolution of an underlying smooth-muscle lineage-derived program characterized by activation of E2F1 and downstream effectors. Recurrently amplified or highly expressed genes in LMS were identified, including IGF1R and genes involved in retinoid signaling pathways. Though the majority of expressed transcripts were conserved across LMS samples, three separate subtypes were identified that were enriched for muscle-associated transcripts (conventional LMS), immune markers (inflammatory LMS), or a uterine-like gene-expression program (uterogenic LMS). Each of these subtypes expresses a unique subset of genes that may be useful in the management of LMS: IGF1R was enriched in conventional LMS, worse disease-specific survival was observed in inflammatory LMS, and prolactin was elaborated by uterogenic LMS. These results extend our understanding of LMS biology and identify several strategies and challenges for further translational investigation.Implications: LMS has a recurrent oncogenic transcriptional program and consists of molecular subtypes with biological and possible clinical implications.

show abstract

Section: Discussionmentioning

confidence: 99%

Oncogenic Gene-Expression Programs in Leiomyosarcoma and Characterization of Conventional, Inflammatory, and Uterogenic Subtypes

Hemming

Fan

Raut

et al. 2020

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…No deaths were noted in the AR expression group, and the 5-year overall survival in the AR-negative expression group was 54.8% ( p = 0.014). Moreover, the co-expression of different steroid receptors (ER and/or PR) with AR was associated with significantly better 5-year disease-free survival and overall survival [ 146 ].…”

Section: Available Immunohistochemical Markersmentioning

confidence: 99%

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium

Rubisz

Ciebiera

Hirnle

et al. 2019

IJMS

View full text Add to dashboard Cite

Uterine leiomyomas (LMs), currently the most common gynecological complaint around the world, are a serious medical, social and economic problem. Accurate diagnosis is the necessary prerequisite of the diagnostic-therapeutic process. Statistically, mistakes may occur more often in case of disease entities with high prevalence rates. Histopathology, based on increasingly advanced immunohistochemistry methods, is routinely used in the diagnosis of neoplastic diseases. Markers of the highest sensitivity and specificity profiles are used in the process. As far as LMs are concerned, the crux of the matter is to identify patients with seemingly benign lesions which turn out to be suspicious (e.g., atypical LM) or malignant (e.g., leiomyosarcoma (LMS)), which is not uncommon. In this study, we present the current state of knowledge about the use of immunohistochemical markers in the differential diagnosis of LM, atypical LM, smooth muscle tumors of uncertain malignant potential (STUMP), and LMS, as well as their clinical predictive value.

show abstract

“…Moreover, ER and PR expression also represent a favourable prognostic factor associated with improved overall survival in US patients [ 3 ], and the co-expression of ER and/or PR with the androgen receptor (AR) is associated with significantly better 5-year DFS and OS, compared to patients with negative AR. AR may be an independent prognostic marker regardless of ER/PR [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

New Insights into Hormonal Therapies in Uterine Sarcomas

Maccaroni

Lunerti

Agostinelli

et al. 2022

Cancers

View full text Add to dashboard Cite

Uterine sarcoma (US) is a rare mesenchymal malignant cancer type, accounting for 3–7% of uterine malignancies. US prognosis is still poor due to high local and distant recurrence rates. As for molecular features, US may present variable oestrogen receptor (ER) and progesterone receptor (PR) expressions, mostly depending on histotype and grading. Surgery represents the mainstay of treatment for early-stage disease, while the role of adjuvant chemotherapy or local radiotherapy is still debated and defined on the basis of histotype, tumour grading and stage. In metastatic setting, uterine sarcomas’ treatment includes palliative surgery, a metastases resection, chemotherapy, hormonal therapy and targeted therapy. As for the chemotherapy regimen used, drugs that are considered most effective are doxorubicin (combined with ifosfamide or alone), gemcitabine combined with docetaxel and, more recently, trabectedin or pazopanib. Hormonal therapies, including aromatase inhibitors (AIs), progestins and gonadotropin-releasing hormone analogues (GnRH-a) may also represent an effective option, in particular for low-grade endometrial stromal sarcoma (LGESS), due to their favourable toxicity profile and patients’ compliance, while their role is still under investigation in uterine leiomyosarcoma (uLMS), high-grade endometrial stromal sarcoma (HGESS), undifferentiated uterine sarcoma (USS) and other rarer US. The present review aims to analyse the existing evidence and future perspectives on hormonal therapies in US, in order to clarify their potential role in daily clinical practice.

show abstract

Androgen receptor as a prognostic biomarker and therapeutic target in uterine leiomyosarcoma

Cited by 15 publications

References 34 publications

Oncogenic Gene-Expression Programs in Leiomyosarcoma and Characterization of Conventional, Inflammatory, and Uterogenic Subtypes

Oncogenic Gene-Expression Programs in Leiomyosarcoma and Characterization of Conventional, Inflammatory, and Uterogenic Subtypes

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium

New Insights into Hormonal Therapies in Uterine Sarcomas

Contact Info

Product

Resources

About