Design: Case-cohort biomarker validation within a randomised trial
Population: 257 patients with early-stage classic Hodgkin lymphoma (EORTC-GELA H9)
Primary outcome: Progression-free survival
Effect: c-MET HR 0.75 (95% CI 0.46 to 1.24); HLA II HR 0.85 (0.50 to 1.45); CD68 HR 0.86 (0.52 to 1.44)

Three of the most promising tissue biomarkers in classic Hodgkin lymphoma were tested on diagnostic biopsies from patients in the EORTC-GELA H9 randomised trial of early-stage disease. A case-cohort design included 257 patients with 105 progression events, and progression-free survival was the outcome.

c-MET was expressed by tumour cells in 67% of evaluable cases and surface HLA class II in 51%; CD68 was scored by stained area, with high defined as above the median of 9.4%. None was associated with progression-free survival: hazard ratios were 0.75 (95% CI 0.46 to 1.24) for c-MET, 0.85 (0.50 to 1.45) for HLA class II and 0.86 (0.52 to 1.44) for CD68. Because no single marker was associated, combinations were not tested.

The authors note that risk-adapted treatment in the trial, the exclusion of advanced-stage disease, and scoring difficulty may have contributed. But a validation inside a randomised trial cohort is the right test, and these markers failed it.

Do not add c-MET, HLA class II or CD68 staining to routine Hodgkin lymphoma reports for prognosis.
Keep risk stratification in early-stage disease on established clinical factors and PET response.
Be sceptical of tissue prognostic markers until they are validated in trial cohorts.

Why it matters

It removes three candidate stains from the prognostic shortlist, sparing laboratories work that would not change care.

The statistics, in plain English

Each hazard ratio's confidence interval crosses 1, so none showed a reliable link with progression. The intervals are wide, so a modest effect cannot be fully excluded, but nothing here supports routine use.