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AS17. Screening/Early detection
EV404/#935  Altered expression of kinetochore proteins Nuf2 and Hec1 in cervical pre-cancer and cancer
  1. Padma Naik1,2,3,
  2. Katharine Astbury2,
  3. Helen Keegan1,2,3,
  4. Victoria Malone1,2,3,
  5. Roisin O’Connor1,4,
  6. Prerna Tewari1,2,3,
  7. Sharon O’Toole2,5,
  8. Bernardo Macondes3,
  9. Kate Thompson3,
  10. Tom D’Arcy2,6,
  11. Cara Martin1,2,3 and
  12. John O’Leary1,2,3
  1. 1Trinity St James Cancer Institute, Histopathology, Dublin, Ireland
  2. 2Trinity College Dublin, Cerviva Research Consortium, Dublin, Ireland
  3. 3Coombe Hospital,, Molecular Pathology Laboratory, The, Dublin, Ireland
  4. 4Trinity College Dublin, Division of Oral and Maxillofacial Surgery, Dublin, Ireland
  5. 5Trinity College Dublin, Obstetrics and Gynaecology/Histopathology, Dublin, Ireland
  6. 6Trinity-St James’s Cancer Institute, St. James’s Hospital, Department of Gynaecological Oncology, Dublin, Ireland

Abstract

Introduction Nuf2 and Hec1, key components of the kinetochore, play a crucial role in the spindle checkpoint control, and kinetochore functionality and are seen as key players in tumorigenesis. Overexpression of Nuf 2 and Hec1 has been detected in a variety of human cancers, including lung, breast and liver cancers. This study aimed to determine expression of nuf2 and Hec1 at RNA and protein levels in cervical cancer and pre-cancer, to a). map expression of the proteins in cervical pre-cancer and cancer and b). to determine whether these are suitable biomarkers for cervical pre-cancer and cancer.

Methods Gene expression profiling of cervical cancer cell lines and normal cervical RNA was performed using Affymetrix GeneChip arrays. Nuf2 and Hec1 expression was confirmed using TaqMan RT PCR. Nuf2 and Hec1 protein expression in formalin-fixed paraffin-embedded normal cervical epithelium and cervical intraepithelial neoplasia (CIN) specimens was assessed by immunohistochemistry (60 cases representing all Normal, CIN1 and CIN2+).

Results Nuf2 and Hec1 mRNA were significantly over-expressed in cervical cancer cell lines compared to normal cervix. Immunohistochemistry demonstrated focal basal epithelial cell staining for Hec1 is seen in the normal cervix. Strong Hec1 positivity was seen in all CIN cases, while Nuf2 staining varied from moderate to strong staining in CIN 1, with more variable staining patterns in high grade CIN.

Conclusion/Implications Nuf2 and Hec1 over-expression in CIN and cervical cancer suggest their potential use as biomarkers. This is the first report of their over-expression in cervical pre-neoplastic and neoplastic disease.

https://doi.org/10.1136/ijgc-2024-IGCS.525

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