Implications of the Hippo Pathway Dysregulation in Uterine Leiomyosarcoma

Anticancer Res. 2024 Aug;44(8):3331-3336. doi: 10.21873/anticanres.17152.

Abstract

Background/aim: Uterine leiomyosarcomas (uLMS) are the most common mesenchymal tumors of the female genital tract. uLMS genetics encompass complex karyotypes with no specific molecular alterations. The Hippo pathway has been implicated in the pathogenesis of epithelioid hemangio-endotheliomas and endometrial sarcomas. Hippo pathway effectors are YAP1 and TAZ co-transcriptional factors.

Patients and methods: We studied Hippo pathway in a series of 32 uLMS patients and its association with clinicopathological parameters.

Materials and methods: Immunohistochemical analysis of YAP1 and TAZ proteins accompanied with fluorescent in situ hybridization study of YAP1 gene was performed in patient samples. Age, sex, tumor size, stage at the time of diagnosis and treatment have been analyzed. Overall survival (OS) was calculated from the time of diagnosis until death, loss of follow up or data cut-off.

Results: Hippo signaling was found to be dysregulated in 20 (62.5%) patients with uLMS. Regarding OS we detected a trend of Hippo deregulation, designating it as a positive prognostic factor.

Conclusion: The Hippo pathway is implicated in uLMS oncogenesis, since nuclear expression of YAP1 was detected in 17 (53.1%) of the 32 patients with immunohistochemistry and YAP1 amplification was found in 8 (25%) patients.

Keywords: Hippo pathway; Uterine leiomyosarcoma; YAP1; prognosis.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Adult
  • Aged
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hippo Signaling Pathway*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Leiomyosarcoma* / genetics
  • Leiomyosarcoma* / metabolism
  • Leiomyosarcoma* / pathology
  • Middle Aged
  • Prognosis
  • Protein Serine-Threonine Kinases* / genetics
  • Protein Serine-Threonine Kinases* / metabolism
  • Signal Transduction*
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Uterine Neoplasms* / genetics
  • Uterine Neoplasms* / metabolism
  • Uterine Neoplasms* / pathology
  • YAP-Signaling Proteins* / genetics
  • YAP-Signaling Proteins* / metabolism

Substances

  • Protein Serine-Threonine Kinases
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Transcription Factors
  • Adaptor Proteins, Signal Transducing
  • WWTR1 protein, human
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins