Aldera Alessandro Pietro, Govender Dhirendra
Division of Anatomical Pathology, University of Cape Town, Cape Town, South Africa
JDW Pathology Inc, Cape Town, South Africa.
J Clin Pathol. 2021 Feb 22. doi: 10.1136/jclinpath-2020-207073.
Carbonic anhydrase IX (CAIX) is a transmembrane metalloenzyme which is upregulated in tumour cells under hypoxic conditions. CAIX expression is induced by the accumulation of hypoxia-inducible factor-1α and has several downstream effects, including acidification of the extracellular pH, loss of cellular adhesion and increased tumour cell migration. CAIX is upregulated in a variety of solid organ tumours and has prognostic implications. High CAIX protein expression is a marker of poor prognosis in breast, lung, ovarian and bladder carcinomas. Conversely, low expression is an indicator of poor prognosis in clear cell renal cell carcinoma (CCRCC). CAIX immunohistochemistry is useful diagnostically to identify metastatic CCRCC, and the recently recognised clear cell papillary renal cell carcinoma. There is much interest in targeting CAIX with monoclonal antibodies and small molecule inhibitors. There are several small molecule inhibitors under development which have shown promising results in clinical trials. In this paper, we provide an overview of the role of CAIX in tumourigenesis and outline its use as a prognostic, diagnostic and therapeutic biomarker.
碳酸酐酶IX（CAIX）是一种跨膜金属酶，在缺氧条件下的肿瘤细胞中上调。CAIX的表达由缺氧诱导因子-1α的积累诱导，并具有多种下游效应，包括细胞外pH值酸化、细胞粘附丧失和肿瘤细胞迁移增加。CAIX在多种实体器官肿瘤中上调，并具有预后意义。CAIX蛋白高表达是乳腺癌、肺癌、卵巢癌和膀胱癌预后不良的标志物。相反，低表达是透明细胞肾细胞癌（CCRCC）预后不良的指标。CAIX免疫组化在诊断上有助于识别转移性CCRCC以及最近认识到的透明细胞乳头状肾细胞癌。用单克隆抗体和小分子抑制剂靶向CAIX引起了人们的极大兴趣。有几种正在开发的小分子抑制剂在临床试验中已显示出有希望的结果。在本文中，我们概述了CAIX在肿瘤发生中的作用，并概述了其作为预后、诊断和治疗生物标志物的用途。
