Badvie S, Hanna-Morris A, Andreyev H J N, Cohen P, Saini S, Allen-Mersh T G
Department of Surgery, Chelsea & Westminster Hospital, London, UK.
J Clin Pathol. 2006 Sep;59(9):942-6. doi: 10.1136/jcp.2005.033431. Epub 2006 May 5.
Colorectal cancer is associated with a "field change" of increased proliferation throughout the colonic and rectal mucosa. Both proliferation and apoptosis are disrupted during carcinogenesis. Whether altered apoptosis contributes to this field change of microscopic abnormality is, however, unclear. Bcl-xL is an anti-apoptotic protein that inhibits apoptosis by preventing release of cytochrome c, a recognised pathway to cell death.
To determine whether Bcl-xL inhibition of apoptosis is increased in colorectal mucosa adjacent to colorectal adenocarcinoma over that in normal non-neoplastic colorectal mucosa.
PATIENTS undergoing surgical resection for neoplastic (adenocarcinoma) or non-neoplastic disease of the colorectum (rectal prolapse, diverticular disease or volvulus).
Formalin-fixed, paraffin-wax-embedded surgical colorectal resection specimens were immunostained for Bcl-xL protein. Labelling indices were determined by counting the proportion of positively stained cells in mucosal crypts.
85 patients were studied. Bcl-xL immunostaining was most marked in the upper third of mucosal crypts. It occurred in a minority of samples from non-neoplastic colorectal mucosa, but was seen in most mucosal samples adjacent to colorectal adenocarcinoma. Significant increases (p<0.001) were observed in Bcl-xL labelling indices in the mucosa at 1 cm (n = 46, median labelling index 31.8%, interquartile range 8.3-43.9%) and at 10 cm (n = 52, median labelling index 22.0%, interquartile range 0.0-36.3%) from colorectal carcinoma, compared with normal, non-neoplastic colorectal mucosa (n = 22, median labelling index 0.0%, interquartile range 0.0-0.0%).
The findings are consistent with a field change of inhibited apoptosis in mucosa adjacent to colorectal carcinoma.
结直肠癌与整个结肠和直肠黏膜增殖增加的“场效应改变”相关。在致癌过程中，增殖和凋亡均受到破坏。然而，凋亡改变是否导致这种微观异常的场效应改变尚不清楚。Bcl-xL是一种抗凋亡蛋白，通过阻止细胞色素c的释放来抑制凋亡，这是一种公认的细胞死亡途径。
确定与正常非肿瘤性结直肠黏膜相比，结直肠腺癌旁结直肠黏膜中Bcl-xL对凋亡的抑制作用是否增强。
因结直肠肿瘤性（腺癌）或非肿瘤性疾病（直肠脱垂、憩室病或肠扭转）接受手术切除的患者。
用福尔马林固定、石蜡包埋的结直肠手术切除标本进行Bcl-xL蛋白免疫染色。通过计数黏膜隐窝中阳性染色细胞的比例来确定标记指数。
对85例患者进行了研究。Bcl-xL免疫染色在黏膜隐窝的上三分之一处最为明显。在非肿瘤性结直肠黏膜的少数样本中可见，但在大多数结直肠腺癌旁的黏膜样本中可见。与正常非肿瘤性结直肠黏膜（n = 22，中位标记指数0.0%，四分位间距0.0 - 0.0%）相比，距结直肠癌1 cm处（n = 46，中位标记指数31.8%，四分位间距8.3 - 43.9%）和10 cm处（n = 52，中位标记指数22.0%，四分位间距0.0 - 36.3%）的黏膜中Bcl-xL标记指数显著增加（p<0.001）。
这些发现与结直肠癌旁黏膜中凋亡受抑制的场效应改变一致。
