title: Frequent loss of WWOX expression in breast cancer: correlation with estrogen receptor status.
abstract: WWOX is a cancer gene, spanning the common chromosomal fragile site 16D. Genomic and expression aberrations affecting this gene and locus are common in various neoplasias including breast cancer. The aim of the present study was to evaluate the relationship between WWOX expression at the protein level with respect to clinico-pathological characteristics. We performed immunohistochemical analyses on breast specific tissue microarrays representing, human normal breast epithelium (n = 16), ductal carcinoma in situ (n = 15) and invasive breast cancer cases (n = 203). Staining intensity measurements were objectively determined utilizing an image analysis system. Western blot analyses were also performed on an independent set of 23 invasive breast carcinomas. All normal breast epithelial samples express WWOX protein abundantly while 34% (69/203 cases) of invasive breast carcinomas were 'completely negative' for WWOX expression and an additional 26% (52/203) of cases expressed WWOX very weakly. For DCIS samples five out of 15 (33%) were negative or weak for WWOX staining. Interestingly, we found a statistically significant correlation between WWOX expression and estrogen receptor (ER) status, 27% of ER+ breast carcinomas were completely negative for WWOX expression versus 46% for ER-cases (p = 0.0054). Furthermore, when negative plus weakly WWOX stained cases were considered the difference became more significant with 51% of ER+ cases and 73% for the ER-group, with a p = 0.003. These data indicate that loss of WWOX expression is a common event in breast cancer. It is unclear at this point whether loss of WWOX expression is a consequence of tumor progression or represents a subclass of breast carcinomas. The strong association of WWOX expression with ER status reinforces the suggested role of this protein as an enzyme involved in sex steroid metabolism.
authors.affiliation: Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, TX 78957, USA.
authors.forename: María I
authors.initials: MI
authors.lastname: Nunez
authors.forename: John
authors.initials: J
authors.lastname: Ludes-Meyers
authors.forename: Martín C
authors.initials: MC
authors.lastname: Abba
authors.forename: Hyunsuk
authors.initials: H
authors.lastname: Kil
authors.forename: Nancy W
authors.initials: NW
authors.lastname: Abbey
authors.forename: Robert E
authors.initials: RE
authors.lastname: Page
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.forename: Andrés J P
authors.initials: AJ
authors.lastname: Klein-Szanto
authors.forename: C Marcelo
authors.initials: CM
authors.lastname: Aldaz
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D010088:Oxidoreductases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis*; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D011960:Receptors, Estrogen; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human