Design: Retrospective single-institution cohort of sequenced tumours
Population: 108 molecularly verified clear cell RCCs (54 primary, 54 metastatic)
Primary outcome: CA9, CK7, PAX8 and CD10 staining patterns
Effect: CK7 positive in 30%; primary vs metastatic 45% vs 13% (P=0.001); CA9 negative in 15% of metastases

A single-institution study took renal cell carcinomas confirmed as clear cell by sequencing (VHL alteration or 3p loss) and reviewed their CA9, CK7, PAX8 and CD10 staining. Of 125 cases, 108 had immunohistochemistry: 54 primary and 54 metastatic tumours.

CK7 was positive in 30% overall, diffusely in 16%. It was more common in primary than metastatic tumours (45% vs 13%), in low- and intermediate-grade architectural patterns (67% vs 17% in high-grade), and in PBRM1 wild-type tumours. CA9 was negative only in metastases (15%). BAP1-mutated tumours had higher-grade patterns and tended to lose CD10.

The classic profile of clear cell RCC — CA9 positive, CK7 negative — does not hold for a meaningful minority. A CK7-positive or CA9-negative tumour can still be clear cell, especially at a metastatic site, so these stains should not overrule morphology and, where available, molecular testing.

Do not exclude clear cell RCC on CK7 positivity alone; 30% of confirmed cases were positive.
Expect CA9 loss in some metastatic clear cell RCC; 15% of metastases were negative.
Use morphology and, where available, VHL or 3p testing when the stain profile is atypical.
Note high-grade architectural patterns, which tracked with BAP1 mutation and CD10 loss.

Why it matters

Textbook stain profiles were built on morphologically selected tumours, and genetically confirmed cases break them more often.

The statistics, in plain English

Comparisons such as 45% vs 13% CK7 positivity reached significance in a modest sample of 108, but these are single-institution proportions and may differ in other cohorts.