title: Aquaporin 3 Expression Predicts Survival in Patients with HER2-positive Early Breast Cancer.
abstract: OBJECTIVE
  Recent studies have revealed aquaporins (AQPs) as targets for novel anti-tumor therapy since they are likely to play a role in carcinogenesis, tumor progression and invasion. Accordingly, we analyzed the prognostic impact of AQP3 expression and polymorphisms in a number of patients with early breast cancer (EBC).
  
  
  METHODS
  AQP3 expression was investigated on the basis of the immunohistochemistry of tissue microarray specimens from 447 EBC patients who underwent surgery between 2003 and 2008. We scored the staining intensity (0 through 3) and percentage of positive tumor cells (0 through 4); the staining score was defined as sum of these scores used to categorize the AQP3 expression as negative (0 through 2), weak (3 through 5) or strong (6 or more). For AQP3 polymorphisms, seven single nucleotide polymorphisms (SNPs) (rs10813981, rs34391490, rs2228332, rs2227285, rs591810, rs17553719 and rs3860987) were selected using in silico analysis and genotyped using the Sequenom MassARRAY.
  
  
  RESULTS
  A total of 180 (40.3%) patients were identified as AQP3-positive (staining score >2), including 86 (19.2%) cases of strong expression (stating score >5). In a univariate analysis, AQP3 expression was significantly associated with survival for the patients with HER2-over-expressing EBC. Moreover, a multivariate survival analysis revealed that AQP3 expression was an independent prognostic marker of disease-free survival (DFS): hazard ratio (HR)=3.137, 95% confidence interval (CI)=1.079-9.125, p=0.036; distant DFS (DDFS): HR=2.784, 95%CI=0.921-8.414, p=0.070, for the HER2-over-expressing EBC patients. Meanwhile, none of selected AQP3 polymorphisms were related to AQP3 expression in tumor tissue or survival in the current study.
  
  
  CONCLUSIONS
  AQP3 expression in tumor tissue may be considered as a potential prognostic marker in patients with HER2-over-expressing EBC after curative surgery.
authors.affiliation: Department of Surgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Sunhee
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea yschae@knu.ac.kr phy123@knu.ac.kr.
authors.forename: Yee Soo
authors.initials: YS
authors.lastname: Chae
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Byung Woog
authors.initials: BW
authors.lastname: Kang
authors.affiliation: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jong Gwang
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Department of Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Wan Wook
authors.initials: WW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jin Hyang
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea yschae@knu.ac.kr phy123@knu.ac.kr.
authors.forename: Ho Yong
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Surgery, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D051400:Aquaporin 3 / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D051400:Aquaporin 3; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Early breast cancer; aquaporin 3; polymorphism; prognosis