Poster Presentation 35th Lorne Cancer Conference 2023

Establishing patient derived xenograft models for ovarian granulosa cell tumours (#340)

Trang Minh Tran 1 2 , Gwo Yaw Ho 2 3 , Jessica Wu 2 , Joshua Ooi 2 , Janet Chang 2 , Tom Jobling 3 , Rhiannon Dudley 1 3 , Maria Alexiadis 1 , Trang Nguyen 1 , Peter J. Fuller 1 3 , Simon Chu 1
  1. Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. School of Clinical Sciences, Monash University, Clayton, VIC, Australia
  3. Monash Health, Clayton, VIC, Australia

Background

Adult granulosa cell tumours (GCT) are a rare subset of ovarian cancer (~5%) which arise from the granulosa cells of the ovarian follicle. The vast majority of GCT are characterised by a pathognomonic somatic mutation in the FOXL2 gene (FOXL2C134W). A unique feature of GCT is their propensity for late recurrence, which cannot be predicted. Nor is it possible to predict tumour behaviour likely to lead to the patient’s demise. Women with recurrent and/or aggressive GCT have few therapeutic options and ~80% will die of their disease. Treatment regimen largely based on those employed for epithelial ovarian cancer are of limited benefit. Therefore, there is an urgent need to understand the molecular mechanisms that contribute to GCT tumorigenesis in order to identify novel therapeutic strategies. There is a paucity of pre-clinical models, hindering GCT research progress. Fresh viable GCT tissue is an invaluable research resource, and we aim to utilise these biospecimens to develop patient-derived xenograft (PDX) models.

Methods

A surgical specimen from a recurrent GCT patient operated at Monash Health was collected in tissue media and 1-2mm tumour fragments were implanted subcutaneously in NOD-scid-gamma major histocompatibility complexes knock-out (NSG MHCnull) mice. Mice (n=7) were observed up to 6 months for tumour engraftment.

Results

Six months post-transplantation, two mice were euthanised and at autopsy, small tumour engraftments (4-5mm) at the surgical sites were observed. The palpable mass was observed to be similar to soft fatty deposits. Upon histopathological analysis and genotyping, the cells showed classic coffee bean morphology characteristic of GCT, as well as confirmation of the FOXL2C134W mutation

Conclusion

We demonstrate a successful engraftment of GCT subcutaneously in immunocompromised mice. To improve the growth rate of the PDX, we have engrafted a more recent recurrent GCT sample into more highly vascularised tissues, intra-renal capsule and intra-peritoneal cavity, of NSG MHCnull mice (n=9). The success of the PDX program is crucial for future GCT research.