Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct;77(4):659-666.
doi: 10.1111/his.14204. Epub 2020 Sep 12.

Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes

Nicholas Baniak  1 , Trevor A Flood  2 , Mark Buchanan  1 , Paola Dal Cin  1 , Michelle S Hirsch  1
Affiliations

Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes

Nicholas Baniak et al. Histopathology. 2020 Oct.

Abstract

Aims: Renal epithelial neoplasms (RENs) can be difficult to subclassify, owing to overlapping morphological features. Carbonic anhydrase 9 (CA9) is a common biomarker for clear cell renal cell carcinoma (CCRCC); however, the sensitivity and specificity across REN subtypes are less clear. The aim of this study was to investigate CA9 expression in RENs, especially those in the differential diagnosis with CCRCC and less common entities, to determine its reliability as a diagnostic biomarker.

Methods and results: CA9 immunostaining was performed on 262 RENs, including 119 CCRCCs and 143 non-CCRCC. Immunostaining was evaluated as negative (0%), rare (1+, 1-10%), focal (2+, 11-50%), or diffuse (3+, >50%). CCRCCs were 3+ CA9-positive in 93% of cases; 4% were CA9-negative. Sixty-seven percent of papillary renal cell carcinomas (RCCs) were 1+/2+ CA9-positive, whereas 33% were CA9-negative. Chromophobe RCCs were nearly always CA9-negative (93%), with 7% showing rare cell reactivity. Clear cell tubulopapillary RCCs (CCTPRCCs) were consistently 3+ CA9-positive, but with a cup-like staining pattern. Fifty-three percent of Xp11.2 RCCs were CA9-negative; however, 6% were 3+ CA9-positive and 12% were 2+ CA9-positive. Two of eight fumarate hydratase-deficient RCCs were 3+ CA9-positive. A small subset of the remaining RCCs showed rare to focal CA9 expression. All oncocytomas and eosinophilic solid and cystic RCCs were CA9-negative.

Conclusions: Overall, diffuse CA9 expression was identified in nearly all CCRCCs and in all CCTPRCCs (high sensitivity); however, CA9 was not entirely specific. At least focal CA9 expression can been seen in a subset of many RCCs, and such findings should be taken into consideration with other morphological, immunophenotypic and clinical findings.

Keywords: CA9; CAIX; Xp11.2; clear; immunohistochemistry; papillary; renal cell carcinoma; translocation.

PubMed Disclaimer

References

    1. Moch H, Humphrey PA, Ulbright TM, Reuter VE eds. World Health Organization classification of tumors of the urinary system and male genital organs. 4th ed. Lyon: IARC Press, 2016.
    1. Hirsch MS, Signoretti S, Dal Cin P. Adult renal cell carcinoma: a review of established entities from morphology to molecular genetics. Surg. Pathol. Clin. 2015; 8; 587-621.
    1. Mehra R, Smith SC, Divaita M, Amin MB. Emerging entities in renal neoplasia. Surg. Pathol. Clin. 2015; 8; 623-656.
    1. Warren AY, Harrison D. WHO/ISUP Classification, grading and pathological staging of renal cell carcinoma: standards and controversies. World J. Urol. 2018; 36; 1913-1926.
    1. Albiges L, Fay AP, McKay RR, Kaymakcalan MD, Choueiri TK. Diagnosis of renal cell carcinoma: a clinician’s perspective. Surg. Pathol. Clin. 2015; 8; 657-662.

MeSH terms

LinkOut - more resources