J Pathol Transl Med.  2016 Jul;50(4):251-257. 10.4132/jptm.2016.03.30.

Aquaporin 1 Is an Independent Marker of Poor Prognosis in Lung Adenocarcinoma

Affiliations
  • 1Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea. chungjh@snu.ac.kr
  • 2Department of Pathology, Soonchunhyang University Hospital, Seoul, Korea.
  • 3Department of Pathology, Second Hospital of Jilin University, Changchun, China.
  • 4Department of Pathology, Fudan University, Shanghai Cancer Center, Shanghai, China.
  • 5Department of Pathology, Kangwon National University Hospital, Chuncheon, Korea.

Abstract

BACKGROUND
Aquaporin 1 (AQP1) overexpression has been shown to be associated with uncontrolled cell replication, invasion, migration, and tumor metastasis. We aimed to evaluate AQP1 expression in lung adenocarcinomas and to examine its association with clinicopathological features and prognostic significance. We also investigated the association between AQP1 overexpression and epithelial-mesenchymal transition (EMT) markers.
METHODS
We examined AQP1 expression in 505 cases of surgically resected lung adenocarcinomas acquired at the Seoul National University Bundang Hospital from 2003 to 2012. Expression of AQP1 and EMT-related markers, including Ecadherin and vimentin, were analyzed by immunohistochemistry and tissue microarray.
RESULTS
AQP1 overexpression was associated with several aggressive pathological parameters, including venous invasion, lymphatic invasion, and tumor recurrence. AQP1 overexpression tended to be associated with higher histological grade, advanced pathological stage, and anaplastic lymphoma kinase (ALK) translocation; however, these differences were not statistically significant. In addition, AQP1 overexpression positively correlated with loss of E-cadherin expression and acquired expression of vimentin. Lung adenocarcinoma patients with AQP1 overexpression showed shorter progression-free survival (PFS, 46.1 months vs. 56.2 months) compared to patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter PFS (hazard ratio, 1.429; 95% confidence interval, 1.033 to 1.977; p=.031).
CONCLUSIONS
AQP1 overexpression was thereby concluded to be an independent factor of poor prognosis associated with shorter PFS in lung adenocarcinoma. These results suggested that AQP1 overexpression might be considered as a prognostic biomarker of lung adenocarcinoma.

Keyword

Aquaporin 1; Adenocarcinoma; Tissue array analysis; Invasion; Epithelial-mesenchymal transition

MeSH Terms

Adenocarcinoma*
Aquaporin 1*
Cadherins
Disease-Free Survival
Epithelial-Mesenchymal Transition
Humans
Immunohistochemistry
Lung*
Lymphoma
Multivariate Analysis
Neoplasm Metastasis
Phosphotransferases
Prognosis*
Recurrence
Seoul
Tissue Array Analysis
Vimentin
Aquaporin 1
Cadherins
Phosphotransferases
Vimentin

Figure

  • Fig. 1. Immunohistochemical expression of aquaporin 1 in lung adenocarcinomas. (A) Apicolateral pattern. (B) Circumferential membranous staining.

  • Fig. 2. Kaplan-Meier survival estimate graphs of progression-free survival (A) and overall survival (B) according to the overexpression of aquaporin 1 in lung adenocarcinoma patients.


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