HLA-A2 expression, stage, and survival in colorectal cancer

Most cancer vaccination trials have been performed in human leukocyte antigen (HLA)-A2 positive populations. Some studies have used HLA-A2 negative patients as control group. However, HLA-type and HLA-expression can interact with tumor biology and possibly affect prognosis. HLA-A2 negative patients might constitute an inadequate control group.

Patients with colorectal cancer were serologically analyzed for HLA-A2 expression. Patients were evaluated for tumor stage, grading, tumor location. Overall survival (OAS) of HLA-A2 positive and HLA-A2 negative patients was compared.

One hundred forty-four patients were evaluable (50% HLA-A2+). Median age was 62 years. UICC stage III or IV: 45.8%. Gender, location, and UICC stage were equally distributed between HLA-A2 subgroups. HLA-A2 positive patients more frequently had grade 3 histology (27.8% vs 13.9%) and chemotherapy (62.9% vs 45.6%). At a median follow-up of 75.8 months, median OAS for the entire study population was 123.3 months, 5-year OAS was 77.5%. No statistically significant difference in OAS was observed between HLA-A2 positive and negative patients (116.5 vs 157 months, 5-year-OAS 74.1+/-11.6% vs 81+/-11.6%, p=0.46). Expectedly, patients with UICC stage I and II disease lived significantly longer than patients with stage III and IV (5-year OAS 94.3% vs 53.4%; p<0.001). A significantly superior OAS was also found for women, independent of stage or HLA status.

HLA-A2 positive patients exhibit poorer tumor differentiation. This might account for a non-significant difference in OAS. The use of HLA-A2 negative patients as control cohort in CRC vaccinations would rather underestimate potential treatment-related survival effects. Therefore, we suggest they constitute a valid auxiliary control group.