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FGFR3 (CD 333)

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 23 November 2012, last major update November 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.
PubMed Search: FGFR3 [title]
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● Member of receptor tyrosine kinase family that controls cell proliferation, differentiation, survival (Cancer Res 2012;72:5843)
● Negative regulator of bone growth; mutations lead to increased receptor activation, causing alterations in endochondral ossification in all long bones, including achondroplasia, hypochondroplasia, thanatophoric dysplasia, SADDAN (J Clin Res Pediatr Endocrinol 2012 Nov 12 [Epub ahead of print], Am J Med Genet A 2011;155A:2426)
● Mutated in urothelial carcinoma (84% of low grade, 17% of high grade, Hum Pathol 2012;43:1573, J Urol 2012;187:310, J Pathol 2011;224:270), low grade prostatic adenocarcinoma (Mod Pathol 2009;22:848)
● Mutated in urothelial papilloma (classic and inverted, Mod Pathol 2009;22:627)
● In myeloma, t(4;14) upregulates FGFR3 and myeloma SET domain protein, and confers poor prognosis (Blood Cancer J 2012;2:e89)
● Activating mutations may cause sytemic epidermal nevi of skin and oral mucosa (BMC Med Genet 2011;12:79)
● Regulates Rituximab's inhibitory effect in B cell lymphoma (J Biol Chem 2012;287:37109)

Uses by pathologists

● For non muscle invasive urothelial carcinoma, surveillance with FGFR3 mutation analysis on urine to partially replace cystoscopy may be cost-effective (J Urol 2012 Nov 6 [Epub ahead of print])
● Help diagnose upper urinary tract urothelial carcinoma (BMC Urol 2012;12:20)
● Help diagnose (with ultrasound) FGFR3-related skeletal dysplasias in utero


FGFR3 and downstream pathways

Mutations in inverted urothelial papilloma

t(4;14) in myeloma

Micro images

Fetal growth plate: (a) osteophytes, (b) chondrocytes

Bladder: urothelial carcinoma

Pancreas: strong cytoplasmic staining of islets, but not glandular epithelium or ducts (Fig 7A)

Prostate: top-BPH, bottom-adenocarcinoma

Salivary gland (Fig 8A)

Skin: malignant acanthosis nigricans
(a) Internal root sheath of normal hair follicle (positive control)
(b) Axillary skin in malignant acanthosis nigricans
(c) Verrucous plaque

Skin: seborrheic keratoses (figure d)

Positive staining - normal

● Pancreatic islets (not acini, not ducts)
● Salivary gland-sublingual (ducts, not epithelial cells)
● Skin: normal hair follicle

Positive staining - disease

● Prostate: nodular hyperplasia, adenocarcinoma
● Skin: malignant acanthosis nigricans, seborrheic keratoses
● Urothelial carcinoma (low grade, occasionally high grade), urothelial papilloma (classic, inverted)

End of Stains > FGFR3 (CD 333)

Ref Updated: 11/23/12

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