Pilbrow S J, Hertzog P J, Linnane A W
Biochemistry Department, Monash University, Clayton, Victoria, Australia.
Br J Cancer. 1992 Oct;66(4):748-57. doi: 10.1038/bjc.1992.351.
The colorectal adenoma-carcinoma sequence was examined in relation to the ectopic expression of the oncofoetal Small Intestinal Mucin Antigen (SIMA), to the development of morphologic changes in the adenoma and perineoplastic mucosa and to indices of malignant potential. Four anti-SIMA MAbs, which define a novel hierarchy of SIMA epitopes in the normal small intestine and adjacent to colorectal cancers, were used in a retrospective immunohistochemical study of Familial Adenomatous Polyposis (FAP, n = 183) and non-familial (n = 44) adenomas. Inappropriate expression of SIMA epitopes was first detected in mucosa adjacent to minute microadenomas larger than three glands, and with increase in size, in increasing amounts within adenomas themselves, but not with microadenomas smaller than three glands or regions of flat mucosa free of adenomas. SIMA epitope expressed in mucosa adjacent to adenomas preceded changes in perineoplastic morphology, which progressed with adenoma growth to resemble transitional mucosa (TM) adjacent to cancers. Thus, the onset of both SIMA expression and morphological changes in TM were consistent with reactive rather than pre-existing field change phenomena. The previously reported hierarchy of four SIMA epitopes (5C5, 3D4, 4D3, 6C5) was also consistently observed in the adenoma-carcinoma sequence, and applied to (i) the order of epitope detection, (ii) the number of positive adenomas and (iii) extent of staining; (iv) the height in the crypt and (v) distance from the adenoma to which epitopes were expressed in perineoplastic mucosa. These observations are consistent with a progression of changes in mucin composition with adenoma development. The percentage of positive adenomas and reactivity scores for each anti-SIMA MAb correlated with increasing adenoma size, degree of dysplasia and growth pattern. SIMA expression appears to predate the earliest reported oncogene and tumour suppressor gene changes, was persistent and increased throughout adenoma development. SIMA epitopes are thus markers of very early neoplastic change, whose expression correlates with malignant potential and may contribute to the accumulation of changes necessary for tumourigenesis.
研究了结直肠腺瘤-癌序列与癌胚性小肠粘蛋白抗原（SIMA）的异位表达、腺瘤及瘤旁黏膜形态学变化的发展以及恶性潜能指标之间的关系。在一项对家族性腺瘤性息肉病（FAP，n = 183）和非家族性（n = 44）腺瘤的回顾性免疫组织化学研究中，使用了四种抗SIMA单克隆抗体，这些抗体确定了正常小肠及结直肠癌旁SIMA表位的新层次结构。SIMA表位的不适当表达首先在大于三个腺管的微小微腺瘤旁的黏膜中检测到，并且随着腺瘤大小的增加，腺瘤自身中表达量也增加，但小于三个腺管的微腺瘤或无腺瘤的扁平黏膜区域中未检测到。腺瘤旁黏膜中表达的SIMA表位先于瘤旁形态学变化，随着腺瘤生长，这种变化进展为类似于癌旁的移行黏膜（TM）。因此，SIMA表达和TM形态学变化的发生均与反应性而非预先存在的场改变现象一致。在腺瘤-癌序列中也一致观察到先前报道的四种SIMA表位（5C5、3D4、4D3、6C5）的层次结构，并应用于（i）表位检测顺序，（ii）阳性腺瘤数量，（iii）染色范围，（iv）隐窝高度，以及（v）瘤旁黏膜中表达表位的腺瘤的距离。这些观察结果与腺瘤发展过程中粘蛋白组成的变化进展一致。每种抗SIMA单克隆抗体的阳性腺瘤百分比和反应性评分与腺瘤大小增加、发育异常程度和生长模式相关。SIMA表达似乎早于最早报道的癌基因和肿瘤抑制基因变化，在腺瘤发展过程中持续存在且增加。因此，SIMA表位是非常早期肿瘤变化的标志物，其表达与恶性潜能相关，可能有助于肿瘤发生所需变化的积累。
