Loss expression of active fragile sites genes associated with the severity of breast epithelial abnormalities.
BACKGROUND
WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.


METHODS
Reverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.


RESULTS
Compared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).


CONCLUSIONS
Expression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.
Wang
Tian-tian
TT
Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Frezza
Eldo E
EE
Ma
Rong
R
Hu
San-yuan
SY
Liu
Chong-zhong
CZ
Zhang
Guang-yong
GY
Wachtel
Mitchell S
MS
Lü
Xiao-mei
XM
Feng
Jin-bo
JB
Lü
Cui-xia
CX
D017766:Acid Anhydride Hydrolases / Q000032:analysis / Q000235:genetics*; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics*; D043283:Chromosome Fragile Sites; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D006965:Hyperplasia; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D010088:Oxidoreductases / Q000032:analysis / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D010088:Oxidoreductases; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase; D000099170:Bis(5'-adenosyl)triphosphatase; C486071:WWOX protein, human