Department of Pathology, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Republic of Korea.
Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institution, Cancer Research Building II, Baltimore, Maryland, United States of America.
PLoS One. 2023 Jan 27;18(1):e0270752. doi: 10.1371/journal.pone.0270752. eCollection 2023.
The role of aquaporin water channels (AQPs) has become an area of great interest in human carcinogenesis. In this report, we have demonstrated the expression of AQP5 in breast cancer by analyzing 591 tissue samples with 7-year follow-ups. By immunochemistry analysis, AQP5 overexpression was observed in 36% (212/591 cases). Then, we have focused on the clinicopathologic variables among cancer tissue samples with strong AQP5 expression (3+ expression, 60/591 cases). The strong AQP5 expression was positively correlated with tumor grade in BCs (p<0.001) and was more frequent in ER/PR-negative BCs than positive ones (14.9% vs. 3.3% and 13.1% vs. 4.8%, respectively, both p<0.001), while Her2/neu-positive status was positively correlated with strong expression of AQP5 (p = 0.005). Of note, breast cancer patients with positive AQP expression (212/591 cases) showed a less favorable breast cancer specific survival rate over 7 years of follow and we further conclude that AQP5 expression is an independent molecular marker associated with worse clinical outcomes. By fluorescence in situ hybridization (FISH), we have identified evidence of gene amplification in 3 of 30 readable breast cancer and further conclude that, in breast cancer, at least some part of AQP5 overexpression is associated with an aberration in the genome level.
水通道蛋白(AQP)在人类肿瘤发生中的作用已成为研究热点。本研究通过对 591 例有 7 年随访资料的乳腺癌组织标本进行分析,证实 AQP5 在乳腺癌中的表达。免疫组化分析发现 36%(212/591 例)的乳腺癌组织存在 AQP5 过表达。然后,我们聚焦于 AQP5 强表达(3+)的乳腺癌组织标本的临床病理变量(60/591 例)。AQP5 的强表达与乳腺癌分级呈正相关(p<0.001),在 ER/PR 阴性乳腺癌中比阳性乳腺癌更为常见(分别为 14.9%和 3.3%,13.1%和 4.8%,均 p<0.001),而 Her2/neu 阳性状态与 AQP5 的强表达呈正相关(p = 0.005)。值得注意的是,AQP 表达阳性的乳腺癌患者(212/591 例)在 7 年随访期间乳腺癌特异性生存率较差,我们进一步得出结论,AQP5 表达是与不良临床结局相关的独立分子标志物。通过荧光原位杂交(FISH),我们在 30 例可读乳腺癌中发现了基因扩增的证据,并进一步得出结论,在乳腺癌中,至少部分 AQP5 过表达与基因组水平的异常有关。