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

Hum Pathol. 2002 Jan;33(1):39-46. doi: 10.1053/hupa.2002.30196.


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/beta-catenin pathway might be involved in the pathogenesis of sporadic and FAP-associated breast fibromatoses. We analyzed somatic beta-catenin and APC gene mutations in 33 breast fibromatoses (32 sporadic and 1 FAP-associated) using immunohistochemistry for beta-catenin, 5q allelic loss assays, and direct DNA sequencing for exon 3 of the beta-catenin gene and the mutation cluster region of the APC gene. Nuclear accumulation of beta-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/beta-catenin pathway were detected in 79% of breast fibromatoses, including activating beta-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/beta-catenin pathway with resultant nuclear translocation of beta-catenin are important in the pathogenesis of both sporadic and FAP-associated breast fibromatosis. The spectrum of beta-catenin and APC alterations is similar to that described for desmoid tumors of the abdomen, paraspinal region, and extremities.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Adenomatous Polyposis Coli Protein / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Chromosomes, Human, Pair 5
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA Primers / chemistry
  • DNA, Neoplasm / analysis
  • Female
  • Fibroma / genetics*
  • Fibroma / metabolism
  • Fibroma / pathology
  • Humans
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Middle Aged
  • Mutation, Missense*
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Trans-Activators*
  • beta Catenin


  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA Primers
  • DNA, Neoplasm
  • Trans-Activators
  • beta Catenin