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Estrogen Receptor b in Fibromatosis. 1 Andrea T. Deyrup, M.D., Ph.D., 2 Maria Tretiakova, M.D., Ph.D. and 2 Anthony G. Montag, M.D. 1 Emory University, Atlanta GA and 2 The University of Chicago, Chicago IL. Fibromatosis. Locally aggressive, non-metastasizing tumor of fibroblasts - PowerPoint PPT Presentation
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Estrogen Receptor 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 Universityof Chicago, Chicago IL
Fibromatosis
• Locally aggressive, non-metastasizing tumor of fibroblasts
• APC (familial) or catenin (sporadic) gene mutation
• Recurrence frequent (positive margin)• No adequate chemotherapy
Hormones in fibromatosis?
• Grow during pregnancy, involute after pregnancy
• Involution after HRT cessation
• Anecdotal response to Tamoxifen or torimifene
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
ER and
1880’s Oophorectomy for breast cancer
50’s-70’s Hormonal ablation
60’s Estrogen binding protein recognized
1986 ER () cloned
1996 ER discovered in rat prostate
DBD F
1 185 251
TAF Hinge LBD
355 549 595
1 45 148 214 304 500 530
16 97 30 59 18
ER
ER
ER vs ER Protein
TAF: Transcription activating functionDBD: DNA binding domainLBD: Ligand binding domain
Tissue Distribution
Breast
Liver CNS
Bone
Cardiovascular
GI
UrogenitalUterus
ER ER ER & ER
Endothelium
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 and ER expression by IHC
0, 1+ (<10%), 2+ (11% to 50%), or 3+ (>50%)
Results
82% ER3+
APC
-Catenin
-Catenin
-catenin
Wnt
Wnt target genes
Proliferation
tcf-lef
-catenin and ER
Co-precipitation
Transactivation reporter genes
Reciprocal recruitment to response elements
Ligand dependent
Ligand independent
Kouzmenko et al, 2004
Serpell et al, 1996Lanari, 1983Brooks et al, 1992Tonelli et al, 2003
Anti-Estrogen Therapy
ResponseDrug Cases
Tamoxifen 4137%
Toremifene 75% 20
Raloxifene 100% 13
Progesterone 55% 11
Future Directions
Clinical trials
Newer ER antagonists
Fibromatosis and SERM’s in vitro
Questions
Should anti-estrogens be considered in non-surgical
fibromatosis?
Should pathologists offer ER IHC?