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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kiewe
Philipp
P
Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
Mansmann
Veit
V
Scheibenbogen
Carmen
C
Buhr
Heinz-Johannes
HJ
Thiel
Eckhard
E
Nagorsen
Dirk
D
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D004363:Drug Utilization; D005260:Female; D005500:Follow-Up Studies; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012737:Sex Factors; D016019:Survival Analysis
D000970:Antineoplastic Agents; D015789:HLA-A2 Antigen