Yousef Arsani, Kim Sung Sun, Krizova Adriana
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Department of Laboratory Medicine, Unity Health, Toronto, ON, Canada.
Cancer Diagn Progn. 2022 Nov 3;2(6):661-667. doi: 10.21873/cdp.10157. eCollection 2022 Nov-Dec.
BACKGROUND/AIM: Carbonic anhydrase 9 (CAIX) is a transmembrane metalloenzyme that regulates cellular adhesion, proliferation, and intra/extracellular pH. It is expressed primarily through a hypoxia-inducible factor 1 (HIF-1)-dependent mechanism. Its over-expression is closely related to somatic mutations in the Von Hippel-Lindau (VHL) gene. Studies have shown that it is over-expressed in renal cell carcinoma. In this study, we aimed to assess the value of CAIX immunostaining as an ancillary diagnostic tool in renal malignancies and medical renal diseases.
Slides of kidney tumors and medical kidney diseases were selected to evaluate CAIX expression. Intensity and staining patterns of CAIX were independently assessed by two pathologists.
Our results showed strong and diffuse box-like membranous staining pattern in the majority of the clear cell renal cell carcinoma (ccRCC) cases (47/59 cases; 94%). A strong, diffuse cup-shaped staining pattern was observed in clear cell papillary RCC. Variable positivity was observed in other RCC (renal cell carcinoma) subtypes. In non-neoplastic renal conditions, the majority of the cases were negative for CAIX, and only a few cases demonstrated patchy non-specific staining. Of note, a single case of transplanted kidney biopsy taken because of delayed graft function showed a focal area of dilated tubules lined by cells with clear cytoplasm and enlarged nuclei with prominent nucleoli. This area showed diffuse membranous staining for CAIX. Two cases of end-stage renal disease showed a focal circumferential membranous staining pattern for CAIX in dilated tubules.
The CAIX immunoreactivity observed in these three cases could be indicative of an early-stage renal cell neoplasm and warrants further investigation.
背景/目的：碳酸酐酶9（CAIX）是一种跨膜金属酶，可调节细胞黏附、增殖以及细胞内/外pH值。它主要通过缺氧诱导因子1（HIF-1）依赖性机制表达。其过表达与冯·希佩尔-林道（VHL）基因的体细胞突变密切相关。研究表明，它在肾细胞癌中过表达。在本研究中，我们旨在评估CAIX免疫染色作为肾恶性肿瘤和内科肾脏疾病辅助诊断工具的价值。
选取肾肿瘤和内科肾脏疾病的切片以评估CAIX表达。由两名病理学家独立评估CAIX的强度和染色模式。
我们的结果显示，大多数透明细胞肾细胞癌（ccRCC）病例（47/59例；94%）呈现强且弥漫的盒状膜染色模式。在透明细胞乳头状肾细胞癌中观察到强且弥漫的杯状染色模式。在其他肾细胞癌（RCC）亚型中观察到不同程度的阳性。在非肿瘤性肾脏疾病中，大多数病例CAIX呈阴性，只有少数病例表现为斑片状非特异性染色。值得注意的是，1例因移植肾功能延迟而进行的移植肾活检显示，局部区域肾小管扩张，内衬细胞质清亮、细胞核增大且核仁突出的细胞。该区域CAIX呈弥漫性膜染色。2例终末期肾病显示，扩张肾小管中CAIX呈局灶性环形膜染色模式。
在这3例中观察到的CAIX免疫反应性可能提示早期肾细胞肿瘤，值得进一步研究。
