Division of Colon and Rectal Surgery, National Defense Medical Centre and Tri-Service General Hospital, Taipei, Taiwan.
Ann Surg Oncol. 2012 Oct;19(11):3432-40. doi: 10.1245/s10434-012-2394-3. Epub 2012 Jun 28.
Despite development in therapeutic strategies, such as neoadjuvant concurrent chemoradiotherapy (CCRT), the prognosis of colorectal cancer remains relatively poor. Cancer stem cells (CSC) with several characteristics can lead to therapeutic resistance. CD133 has been identified as a putative CSC marker in colorectal cancer; however, its functional role still needs elucidation. We verified the role of CD133 with emphasis on expression location and correlated the results of CD133 with clinical outcome in colorectal cancer.
We used immunohistochemistry to investigate the expression of CD133 in samples from 157 patients with colonic adenocarcinoma and from 76 patients with rectal adenocarcinoma who received neoadjuvant CCRT. We also correlated the expression location of CD133 with the clinicopathological parameters and prognosis.
CD133 protein was variably overexpressed in colorectal cancer tissues and was present in three locations: apical and/or endoluminal surfaces, cytoplasm, and lumen. Cytoplasmic CD133 expression level correlated significantly with tumor local recurrence (P = 0.025) and survival of patients with colorectal cancer (P = 0.002), and correlated inversely with tumor regression grading (P = 0.021) after CCRT in patients with rectal cancer.
The expression of CD133 in the cytoplasm is closely associated with local recurrence and patient survival, and may provide a reliable prognostic indicator of tumor regression grading in patients with rectal cancer after CCRT. Cytoplasmic CD133 expression may also help identify the surviving cancer cells in areas with nearly total regression after CCRT.
尽管在治疗策略方面取得了进展,如新辅助同步放化疗(CCRT),但结直肠癌的预后仍然相对较差。具有多种特性的癌症干细胞(CSC)可导致治疗耐药性。CD133 已被鉴定为结直肠癌中的一个潜在的 CSC 标志物;然而,其功能作用仍需要阐明。我们验证了 CD133 的作用,重点研究其表达位置,并将 CD133 的结果与结直肠癌的临床结果相关联。
我们使用免疫组织化学方法检测了 157 例结肠腺癌和 76 例接受新辅助 CCRT 的直肠腺癌患者样本中 CD133 的表达。我们还将 CD133 的表达位置与临床病理参数和预后相关联。
CD133 蛋白在结直肠癌组织中呈不同程度的过表达,存在于三个位置:顶端和/或腔内腔面、细胞质和管腔。细胞质 CD133 表达水平与肿瘤局部复发(P=0.025)和结直肠癌患者的生存(P=0.002)显著相关,与接受 CCRT 的直肠腺癌患者的肿瘤消退分级(P=0.021)呈负相关。
细胞质中 CD133 的表达与局部复发和患者生存密切相关,可能为接受 CCRT 的直肠腺癌患者的肿瘤消退分级提供可靠的预后指标。细胞质 CD133 表达也有助于识别 CCRT 后几乎完全消退区域中的存活癌细胞。