Aquaporin 5 expression is frequent in prostate cancer and shows a dichotomous correlation with tumor phenotype and PSA recurrence

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• 作者：Alexandra Pust ; MD^a ; ¹ ; Dominik Kylies ; MS^a ; ¹ ; Claudia Hube-Magg ; PhD^a ; Martina Kluth ; MA^a ; Sarah Minner ; MD^a ; Christina Koop ; BTA^a ; Tobias Grob ; PhD ; MD^a ; Markus Graefen ; MD^b ; Georg Salomon ; MD^b ; Maria Christina Tsourlakis ; MD^a ; Jakob Izbicki ; MD^c ; Corinna Wittmer ; MD^a ; Hartwig Huland ; MD^b ; Ronald Simon ; PhD^a ; ^{r.simon@uke.de" class="auth_mail" title="E-mail the corresponding author} ; Waldemar Wilczak ; MD^a ; Guido Sauter ; MD^a ; Stefan Steurer ; MD^a ; Till Krech ; MD^a ; Thorsten Schlomm ; MD^b ; ^d ; Nathaniel Melling ; MD^a ; ^c
• 关键词：AQP5 ; Prostate cancer ; Tissue microarray ; Biochemical recurrence ; PSA
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：48
• 期：Complete
• 页码：102-110
• 全文大小：1018 K

文摘

Aquaporin 5 (AQP5) is an androgen-regulated member of a family of small hydrophobic integral transmembrane water channel proteins regulating cellular water homeostasis and growth signaling. To evaluate its clinical impact and relationship with key genomic alterations in prostate cancer, AQP5 expression was analyzed by immunohistochemistry on a tissue microarray containing 12 427 prostate cancers. The analysis revealed weak to moderate immunostaining in normal prostate epithelium. In prostate cancers AQP5 staining levels were more variable and also included completely negative and highly overexpressing cases. Negative, weak, moderate, and strong AQP5 staining was found in 25.0%, 32.5%, 32.5%, and 10.0% of 10 239 interpretable tumors. Comparison of AQP5 expression levels with tumor characteristics showed a dichotomous pattern with both high and low staining levels being linked to unfavorable tumor phenotype. AQP5 was negative in 28%, 23%, 24%, and 35% of tumors with Gleason score ≤3 + 3, 3 + 4, 4 + 3 and ≥4 + 4, while the rate of strongly positive cases continuously increased from 7.0% over 10.0% and 12.0% to 13.0% in cancers with Gleason score ≤3 + 3, 3 + 4, 4 + 3 and ≥4 + 4. AQP5 expression was also related to ERG positivity and phosphatase and tensin homolog (PTEN) deletion (P < .0001 each). Strong AQP5 positivity was seen in 15.5% of ERG-positive and 5.8% of ERG-negative cancers (P < .0001) as well as in 14.7% of cancers with PTEN deletion and 9.4% of cancers without PTEN deletion. Remarkably, both negativity and strong positivity of AQP5 were linked to unfavorable disease outcome. This was however only seen in subgroups defined by TMPRSS2-ERG fusion and/or PTEN deletion. In summary, AQP5 can be both overexpressed and lost in subgroups of prostate cancers. Both alterations are linked to unfavorable outcome in molecularly defined cancer subgroups. It is hypothesized that this dichotomous role of AQP5 is due to two highly different mechanisms as to how the protein can influence cancer cells, that is, hydraulic motility regulation and Ras/MAPK pathway activation.