Design: Single-institution retrospective cohort with sequencing
Population: 108 molecularly confirmed clear cell RCCs (54 primary, 54 metastatic)
Primary outcome: CA9, CK7, PAX8 and CD10 staining patterns
Effect: CK7 positive 30% (primary 45% vs metastatic 13%); CA9 negative in 15% of metastases

Immunohistochemical profiles of clear cell renal cell carcinoma were originally defined on tumours chosen by morphology. This study took 108 tumours confirmed as clear cell by sequencing (VHL alteration or 3p loss), 54 primaries and 54 metastases, and reviewed CA9, CK7, PAX8 and CD10 staining against architecture and mutations.

CK7 was positive in 30% overall and diffusely strong in 16%. It was more common in primaries than metastases (45% vs 13%) and in low- and intermediate-grade patterns than high-grade ones. CA9 was negative in 15% of metastases and never in primaries. PBRM1-mutated tumours tended towards a CK7-negative, CA9-positive, PAX8-negative profile, while BAP1-mutated tumours had higher-grade patterns and lacked CD10.

For sign-out, the implication is that CK7 positivity does not by itself exclude clear cell carcinoma, and a negative CA9 in a metastasis does not exclude a renal primary.

This is a single-institution series enriched for sequenced tumours, which may not represent routine cases.

Do not exclude clear cell RCC on CK7 positivity alone, particularly in low-grade primaries.
Do not exclude a renal primary on CA9 negativity in a metastasis.
Interpret PAX8 negativity with caution in PBRM1-mutated tumours.
Consider molecular confirmation where the immunoprofile is discordant with morphology.

Why it matters

Panels built on classic cases can mislead in exactly the metastatic and high-grade tumours where the diagnosis matters most.

The statistics, in plain English

The comparisons rest on 54 primaries and 54 metastases, so percentages in subgroups such as PBRM1 status are based on small numbers and are imprecise.