The Polyposis Registry, St Mark's Hospital, Harrow, UK.
London Research Institute, Cancer Research UK, London, UK.
Colorectal Dis. 2011 Apr;13(4):387-392. doi: 10.1111/j.1463-1318.2009.02159.x.
In patients with familial adenomatous polyposis (FAP), ileoanal pouch cancer is rare whereas rectal cancer is common, despite polyp initiation at the two sites being similar at the molecular level. This study investigated whether the disparity in adenoma aggressiveness reflects underlying differences in histogenesis.
Normal mucosal biopsies and 2-3 mm adenomas from patients with FAP were dissected into individual crypts. Crypt area, morphology, fission and mitoses were analysed for crypts from pouch, rectum and supra-anastomotic ileum. Immunohistochemistry of similar archival samples was performed for lysozyme, β-catenin and TP53 expression.
The morphology of normal crypts was similar at each site, although crypt area differed. The area of normal pouch crypts was intermediate between rectum and ileum. The area of adenomatous crypts of rectum and pouch was similar, but the latter had increased asymmetrical fission. Crypt mitoses were proportional to area in all tissues, but crypt fission was reduced in adenomatous crypts from the rectum compared with the pouch. Pouch adenomas retained lysozyme expression as seen in normal ileum. Nuclear β-catenin accumulation was similar, but TP53 expression was increased in rectal adenomas.
Diminutive polyps from rectum and pouch differ in morphology and proliferation. Aggressiveness in rectal polyps is not conferred by increased crypt proliferation, fission, or activation of the Wnt signalling pathway. Increased TP53 expression suggests other molecular mechanisms may be responsible. While crypt mitoses are proportional to crypt area, the threshold for fission may be site specific, indicating that tissue origin may influence histogenesis and thus malignant potential.
在家族性腺瘤性息肉病（FAP）患者中，尽管在分子水平上两个部位的息肉起始相似，但直肠腺癌少见，而直肠腺癌常见。本研究旨在探讨腺瘤侵袭性的差异是否反映了潜在的组织发生差异。
将 FAP 患者的正常黏膜活检和 2-3mm 大小的腺瘤分为单个隐窝。分析来自直肠、 pouch 和吻合口以上回肠的隐窝的隐窝面积、形态、分裂和有丝分裂。对类似的存档样本进行溶菌酶、β-连环蛋白和 TP53 表达的免疫组织化学染色。
尽管隐窝面积不同，但每个部位的正常隐窝形态相似。 pouch 正常隐窝的面积介于直肠和回肠之间。直肠和 pouch 腺瘤隐窝的面积相似，但后者的不对称分裂增加。在所有组织中，隐窝有丝分裂与面积成正比，但与 pouch 相比，直肠腺瘤隐窝的分裂减少。 pouch 腺瘤保留了在正常回肠中所见的溶菌酶表达。核β-连环蛋白的积累相似，但直肠腺瘤中 TP53 表达增加。
直肠和 pouch 的微小息肉在形态和增殖上存在差异。直肠息肉的侵袭性不是由于隐窝增殖、分裂或 Wnt 信号通路的激活增加所致。TP53 表达增加提示可能存在其他分子机制。虽然隐窝有丝分裂与隐窝面积成正比，但分裂的阈值可能是特定部位的，表明组织起源可能影响组织发生，从而影响恶性潜能。
