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FOXA1 expression and its association with mucin expression and KRAS mutation in ovarian mucinous tumors: implications

Men Yuan1, Harumi Saeki2, Takuo Hayashi1

  • 1Department of Human Pathology, Faculty of Medicine, Juntendo University, Tokyo, Japan.

Virchows Archiv : an International Journal of Pathology
|February 24, 2025
PubMed
Summary

Forkhead box A1 (FOXA1) is commonly expressed in ovarian mucinous tumors and correlates with mucin expression. Its co-occurrence with KRAS mutations may drive tumor progression and intestinal differentiation.

Keywords:
KRASFOXA1MucinOvarian mucinous tumorOvarian tumor

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Area of Science:

  • Gynecologic Oncology
  • Molecular Pathology
  • Tumor Biology

Background:

  • Forkhead box A1 (FOXA1) is a transcription factor implicated in epithelial development and differentiation.
  • The role of FOXA1 in ovarian mucinous tumors, particularly its association with mucin expression and KRAS mutations, requires further elucidation.
  • Understanding these relationships is crucial for clarifying FOXA1's involvement in ovarian tumor progression and differentiation.

Purpose of the Study:

  • To investigate forkhead box A1 (FOXA1) expression patterns in ovarian mucinous tumors.
  • To assess the association between FOXA1 expression, mucin expression (MUC2, MUC5AC, MUC6), and KRAS mutation status.
  • To clarify the role of FOXA1 in the progression and differentiation of mucinous ovarian tumors.

Main Methods:

  • Immunohistochemistry was employed to analyze FOXA1, MUC2, MUC5AC, and MUC6 expression in 57 normal/benign tissues and 324 ovarian epithelial tumors (110 mucinous, 214 others).
  • KRAS mutation analysis was performed on the tumor samples.
  • Statistical analyses were conducted to determine associations between markers and clinicopathological features.

Main Results:

  • Strong nuclear FOXA1 staining was observed in normal ovarian epithelium and Brenner tumors.
  • FOXA1 expression was significantly associated with mucinous histology and increased progressively with the grade of mucinous tumors (cystadenoma to carcinoma).
  • MUC2 expression and KRAS mutations also showed a trend of increase with malignancy, with KRAS mutations enriched in FOXA1-negative cystadenomas. FOXA1 expression and KRAS mutations showed a stepwise increase from cystadenoma to carcinoma.

Conclusions:

  • Mucinous ovarian tumors frequently express FOXA1, with expression levels correlating with tumor grade.
  • The co-occurrence of KRAS mutations and FOXA1 expression appears to be a significant factor in the intestinal differentiation and progression of mucinous ovarian tumors.
  • FOXA1 may serve as a valuable biomarker in understanding the pathogenesis of mucinous ovarian neoplasms.