Raf kinase inhibitor protein expression in smooth muscle tumours of the uterus: a diagnostic marker for leiomyosarcoma?

Stefania Greco; Joana Pinheiro; Diana Cardoso-Carneiro; Federica Giantomassi; Pamela Pellegrino; Giulia Scaglione; Giovanni Delli Carpini; Andrea Ciavattini; Gian Franco Zannoni; Gaia Goteri; Olga Martinho; Pasquapina Ciarmela

doi:10.1016/j.rbmo.2024.103816

Raf kinase inhibitor protein expression in smooth muscle tumours of the uterus: a diagnostic marker for leiomyosarcoma?

Reprod Biomed Online. 2024 Jan 13;48(6):103816. doi: 10.1016/j.rbmo.2024.103816. Online ahead of print.

Affiliations

¹ Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy.
² Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal.; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
³ Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
⁴ Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.
⁵ Department of Specialist and Odontostomatological Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy.
⁶ Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy.. Electronic address: p.ciarmela@univpm.it.

PMID: 38608337
DOI: 10.1016/j.rbmo.2024.103816

Abstract

Research question: What is the expression pattern of Raf kinase inhibitory protein (RKIP) in different subtypes of leiomyoma (usual type, cellular, apoplectic or haemorrhagic leiomyoma, leiomyoma with bizarre nuclei and lipoleiomyoma) and leiomyosarcoma specimens, and what is its biological role in leiomyosarcoma cells?

Design: Leiomyoma and leiomyosarcoma specimens underwent immunohistochemistry staining. Leiomyosarcoma SK-LMS-1 cell line was RKIP knocked down and RKIP overexpressed, and cell viability, wound healing migration and clonogenicity assays were carried out.

Results: A higher immunohistochemical expression of RKIP was observed in bizarre leiomyomas, than in usual-type leiomyomas. Decreased expression was also found in cellular leiomyoma, with generally absent staining in leiomyosarcomas. Upon RKIP expression manipulation in SK-LMS-1 cell line, no major differences were observed in cell viability and migration capacity over time. RKIP knockout, however, resulted in a significant increase in the cell's ability to form colonies (P = 0.011).

Conclusion: RKIP distinct expression pattern among leiomyoma histotype and leiomyosarcoma, and its effect on leiomyosarcoma cells on colony formation, encourages further studies of RKIP in uterine smooth muscle disorders.

Keywords: Histopathology; Leiomyosarcoma; Markers; RKIP; Uterine fibroid.