Kaprio Tuomas, Fermér Christian, Hagström Jaana, Mustonen Harri, Böckelman Camilla, Nilsson Olle, Haglund Caj
Department of Surgery, Helsinki University Central Hospital, PO Box 440, 00029 Helsinki HUS, Finland.
BMC Cancer. 2014 Jul 8;14:493. doi: 10.1186/1471-2407-14-493.
Over two decades ago, a proposal was that two different colorectal cancer (CRC) entities existed, based on tumour location either proximal (right) or distal (left) of the splenic flexure. Proximal and distal tumours exhibit different clinical, epidemiological, and biological characteristics. Improvement of the prognostic evaluation of CRC requires new molecular markers. Podocalyxin-like 1 (PODXL), an anti-adhesive transmembrane sialomucin, is associated with an aggressive tumour phenotype and poor prognosis. For colorectal cancer, it has been suggested to be a marker of poor prognosis. The aim of this study was to investigate the role of PODXL in CRC by use of a novel monoclonal antibody.
In 1983-2001, 840 consecutive colorectal cancer patients were treated at Helsinki University Central Hospital, of whom 767 were successfully scored for PODXL immunohistochemical expression from tumour tissue microarrays by use of a novel monoclonal in-house antibody. Associations of PODXL expression and tumour location with other clinicopathological variables were explored by Fisher's exact-test, linear-by- linear association test, and binary logistic regression. Survival analyses were done by the Kaplan-Meier method and Cox proportional hazards model.
PODXL protein expression was high in 44 (5.7%) specimens. High expression associated strongly with poor differentiation (p < 0.0001), advanced stage (p = 0.011), and location of the tumour in the right hemicolon (RHC) (p < 0.001). Tumours of the RHC were more poorly differentiated (p < 0.0001) and showed higher PODXL expression (p < 0.001).High PODXL expression associated significantly with higher risk for disease-specific death from CRC (hazard ratio (HR) = 2.00; 95% confidence interval (CI) 1.31-3.06, p = 0.001) and also in the subgroups of left hemicolon (LHC) cancers (HR = 2.60; 95% CI 1.45-4.66, p = 0.001) and rectal cancers (HR = 3.03; 95% CI 1.54-5.60, p = 0.001). Results remained significant in multivariable analysis (respectively, HR = 1.82; 95% CI 1.15-2.86, p = 0.01; HR = 2.59; 95% CI 1.41-4.88, p = 0.002; and HR = 2.69; 95% CI 1.30-5.54, p = 0.007).
Podocalyxin was an independent factor for poor prognosis in colorectal cancer and in the subgroups of left hemicolon and rectum. This is, to our knowledge, the first evidence of such difference in PODXL expression, its function possibly being dependent upon tumour location.
二十多年前，有人提出存在两种不同的结直肠癌（CRC）实体，这是基于肿瘤位于脾曲近端（右侧）或远端（左侧）。近端和远端肿瘤表现出不同的临床、流行病学和生物学特征。改善结直肠癌的预后评估需要新的分子标志物。足状黏蛋白样1（PODXL）是一种抗黏附跨膜唾液酸黏蛋白，与侵袭性肿瘤表型和不良预后相关。对于结直肠癌，它被认为是预后不良的标志物。本研究的目的是通过使用一种新型单克隆抗体来研究PODXL在结直肠癌中的作用。
1983年至2001年，840例连续的结直肠癌患者在赫尔辛基大学中心医院接受治疗，其中767例通过使用新型内部单克隆抗体从肿瘤组织微阵列中成功对PODXL进行免疫组化表达评分。通过Fisher精确检验、线性-线性关联检验和二元逻辑回归探讨PODXL表达和肿瘤位置与其他临床病理变量的关联。生存分析采用Kaplan-Meier方法和Cox比例风险模型进行。
44份（5.７%）标本中PODXL蛋白表达较高。高表达与低分化（p<0.0001）、晚期（p = 0.011）以及肿瘤位于右半结肠（RHC）显著相关（p<0.０01）。RHC的肿瘤分化更差（p<0.0001）且PODXL表达更高（p<0.001）。高PODXL表达与结直肠癌疾病特异性死亡风险显著相关（风险比（HR）= 2.00；95%置信区间（CI）1.31 - 3.06，p = 0.001），在左半结肠（LHC）癌亚组（HR = 2.60；95% CI 1.45 - 4.66，p = 0.001）和直肠癌亚组（HR = 3.03；95% CI 1.54 - 5.60，p = 0.001）中也是如此。在多变量分析中结果仍然显著（分别为HR = 1.82；95% CI 1.15 - 2.86，p = 0.01；HR = 2.59；95% CI 1.41 - 4.88，p = 0.002；以及HR = 2.69；95% CI 1.30 - 5.54，p = 0.007）。
足状黏蛋白是结直肠癌以及左半结肠和直肠亚组中预后不良的独立因素。据我们所知，这是PODXL表达存在这种差异的首个证据，其功能可能取决于肿瘤位置。
