Fibromatosis of the breast and mutations involving the APC/β-catenin pathway

Susan C. Abraham, Carol Reynolds, Jae Hyuk Lee, Elizabeth A. Montgomery, Blaire L. Baisden, Alyssa M. Krasinskas, Tsung Teh Wu

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Abstract

Fibromatoses of the breast are nonmetastasizing tumors, but can be infiltrative and locally recurrent. Breast fibromatoses are rare, and their specific genetic alterations have not been elucidated. However, their occasional occurrence in patients with familial adenomatous polyposis (FAP) and their morphologic identification with other deep fibromatoses (desmoid tumors) suggest that alterations of the APC/β-catenin pathway might be involved in the pathogenesis of sporadic and FAP-associated breast fibromatoses. We analyzed somatic β-catenin and APC gene mutations in 33 breast fibromatoses (32 sporadic and 1 FAP-associated) using immunohistochemistry for β-catenin, 5q allelic loss assays, and direct DNA sequencing for exon 3 of the β-catenin gene and the mutation cluster region of the APC gene. Nuclear accumulation of β-catenin was present in the stromal tumor cells in most (82%) cases but not in normal stroma or mammary epithelial cells. Somatic alterations of the APC/β-catenin pathway were detected in 79% of breast fibromatoses, including activating β-catenin gene mutations in 15 cases and somatic APC alterations (mutation or 5q allelic loss or both) in 11. These findings indicate that alterations of the APC/β-catenin pathway with resultant nuclear translocation of β-catenin are important in the pathogenesis of both sporadic and FAP-associated breast fibromatosis. The spectrum of β-catenin and APC alterations is similar to that described for desmoid tumors of the abdomen, paraspinal region, and extremities.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalHuman Pathology
Volume33
Issue number1
DOIs
StatePublished - 2002

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Catenins
Fibroma
Breast
Mutation
Adenomatous Polyposis Coli
APC Genes
Aggressive Fibromatosis
Loss of Heterozygosity
Neoplasms
Multigene Family
Stromal Cells
DNA Sequence Analysis
Abdomen
Exons
Extremities
Epithelial Cells
Immunohistochemistry
Breast Neoplasms

Keywords

  • β-catenin
  • APC
  • Breast fibromatosis
  • Mutations

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Abraham, S. C., Reynolds, C., Lee, J. H., Montgomery, E. A., Baisden, B. L., Krasinskas, A. M., & Wu, T. T. (2002). Fibromatosis of the breast and mutations involving the APC/β-catenin pathway. Human Pathology, 33(1), 39-46. https://doi.org/10.1053/hupa.2002.30196

Fibromatosis of the breast and mutations involving the APC/β-catenin pathway. / Abraham, Susan C.; Reynolds, Carol; Lee, Jae Hyuk; Montgomery, Elizabeth A.; Baisden, Blaire L.; Krasinskas, Alyssa M.; Wu, Tsung Teh.

In: Human Pathology, Vol. 33, No. 1, 2002, p. 39-46.

Research output: Contribution to journalArticle

Abraham, SC, Reynolds, C, Lee, JH, Montgomery, EA, Baisden, BL, Krasinskas, AM & Wu, TT 2002, 'Fibromatosis of the breast and mutations involving the APC/β-catenin pathway', Human Pathology, vol. 33, no. 1, pp. 39-46. https://doi.org/10.1053/hupa.2002.30196
Abraham SC, Reynolds C, Lee JH, Montgomery EA, Baisden BL, Krasinskas AM et al. Fibromatosis of the breast and mutations involving the APC/β-catenin pathway. Human Pathology. 2002;33(1):39-46. https://doi.org/10.1053/hupa.2002.30196
Abraham, Susan C. ; Reynolds, Carol ; Lee, Jae Hyuk ; Montgomery, Elizabeth A. ; Baisden, Blaire L. ; Krasinskas, Alyssa M. ; Wu, Tsung Teh. / Fibromatosis of the breast and mutations involving the APC/β-catenin pathway. In: Human Pathology. 2002 ; Vol. 33, No. 1. pp. 39-46.
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