Kiewe Philipp, Mansmann Veit, Scheibenbogen Carmen, Buhr Heinz-Johannes, Thiel Eckhard, Nagorsen Dirk
Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
Int J Colorectal Dis. 2008 Aug;23(8):767-72. doi: 10.1007/s00384-008-0488-y. Epub 2008 May 7.
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.
大多数癌症疫苗试验是在人类白细胞抗原(HLA)-A2阳性人群中进行的。一些研究将HLA-A2阴性患者作为对照组。然而,HLA类型和HLA表达可与肿瘤生物学相互作用,并可能影响预后。HLA-A2阴性患者可能构成不充分的对照组。
对结直肠癌患者进行HLA-A2表达的血清学分析。评估患者的肿瘤分期、分级、肿瘤位置。比较HLA-A2阳性和阴性患者的总生存期(OAS)。
144例患者可评估(50%为HLA-A2+)。中位年龄为62岁。国际抗癌联盟(UICC)III期或IV期:45.8%。性别、位置和UICC分期在HLA-A2亚组之间分布均衡。HLA-A2阳性患者更常出现3级组织学(27.8%对13.9%)和接受化疗(62.9%对45.6%)。中位随访75.8个月时,整个研究人群的中位OAS为123.3个月,5年OAS为77.5%。HLA-A2阳性和阴性患者之间未观察到OAS有统计学显著差异(116.5对157个月,5年OAS 74.1±11.6%对81±11.6%,p = 0.46)。不出所料,UICC I期和II期疾病患者的生存期明显长于III期和IV期患者(5年OAS 94.3%对53.4%;p<0.001)。还发现女性的OAS明显更优,与分期或HLA状态无关。
HLA-A2阳性患者表现出较差的肿瘤分化。这可能是OAS无显著差异的原因。在结直肠癌疫苗接种中将HLA-A2阴性患者用作对照队列可能会低估潜在的治疗相关生存效应。因此,我们建议将其构成一个有效的辅助对照组。