Estrogen Receptor b in Fibromatosis

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Estrogen Receptor b in Fibromatosis
1Andrea T. Deyrup, M.D., Ph.D., 2Maria
Tretiakova, M.D., Ph.D. and 2Anthony G. Montag,
M.D.
1Emory University, Atlanta GA and 2The
University of Chicago, Chicago IL
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Fibromatosis

• Locally aggressive, non-metastasizing tumor of
  fibroblasts
• APC (familial) or b catenin (sporadic) gene
  mutation
• Recurrence frequent (positive margin)
• No adequate chemotherapy

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Hormones in fibromatosis?

• Grow during pregnancy, involute after pregnancy
• Involution after HRT cessation
• Anecdotal response to Tamoxifen or torimifene

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ER in Fibromatosis
Author Year Positive Cases Methodology
Hayry 1982 3/4 Ligand binding
Weiss 1986 1/3 Ligand binding
Lim 1986 5/15 Ligand binding
Maddalozo 1993 2/4 Ligand binding
Rasbridge 1993 0/6 IHC
Devouassoux-Shisheboran 2000 0/33 IHC
Sorensen 2002 0/72 IHC
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ER a and b
1880s Oophorectomy for breast cancer
50s-70s Hormonal ablation
60s Estrogen binding protein recognized
1986 ER (a) cloned
1996 ERb discovered in rat prostate
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ERa vs ERb Protein
ERa
ERb
TAF Transcription activating function DBD DNA
binding domain LBD Ligand binding domain
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Tissue Distribution
ERa
ERb
ERa ERb
Liver
CNS
GI
Cardiovascular
Urogenital
Uterus
Breast
Bone
Endothelium
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Methodology
40 cases of extra-abdominal fibromatosis 11M
29F 5 74 years (mean 33.4, med 32)
Buttock, ext, trunk, neck, flank 9 recurrent
Assessed for ER a and ER b expression by IHC
0, 1 (lt10), 2 (11 to 50), or 3 (gt50)
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Results
82 ERb 3
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b-Catenin
Wnt
APC
b-Catenin
b-catenin
tcf-lef
Wnt target genes
Proliferation
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b-catenin and ERa
Ligand independent
Co-precipitation
Ligand dependent
Transactivation reporter genes
Reciprocal recruitment to response elements
Kouzmenko et al, 2004
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Anti-Estrogen Therapy
Response
Drug
Cases
Tamoxifen
41
37
Toremifene
75
20
Progesterone
55
11
Raloxifene
100
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Serpell et al, 1996 Lanari, 1983 Brooks et al,
1992 Tonelli et al, 2003
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Future Directions

• Clinical trials
• Newer ER antagonists
• Fibromatosis and SERMs in vitro

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Questions
Should anti-estrogens be considered in
non-surgical fibromatosis?
Should pathologists offer ERb IHC?
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