de Bruïne A P, Wiggers T, Beek C, Volovics A, von Meyenfeldt M, Arends J W, Bosman F T
Department of Pathology, University Hospital Maastricht, The Netherlands.
Int J Cancer. 1993 Jul 9;54(5):765-71. doi: 10.1002/ijc.2910540510.
The occurrence of endocrine cells in 350 cases of colorectal adenocarcinoma was studied by immunohistochemistry for chromogranin A (CGA). The hormone profile of endocrine tumor cells, the correlation between endocrine differentiation and presence of other colorectal epithelial-cell lineages and the prognostic relevance of endocrine differentiation in colorectal cancer were investigated. CGA-positive tumor cells were found in 30% of cases, 21% showing moderate positivity and 9.0% extensive positivity. Of CGA-positive tumors, 70% additionally produced neurohormones, mainly indigenous to normal colorectal epithelium: 55% showed immunoreactivity for glucagon-like substances, 20% for serotonin and 10% for somatostatin, PYY and HCG. No immunoreactivity was found for various neurohormones not normally produced by colorectal endocrine cells. CGA-positive tumors tended to be more aggressive than CGA-negative tumors. Especially, tumors with extensive CGA positivity showed shorter survival, which was most apparent within Dukes' stage C. In multivariate analysis, extensive CGA positivity was an independent indicator of poor prognosis. CGA immunoreactivity significantly correlated with mucin production, but not with expression of secretory component (SC), a columnar-cell marker. Mucin production significantly correlated with SC expression. Tumors positive for CGA but not for mucin and/or SC showed the worst prognosis. SC expression was a relatively favorable feature, and mucin-producing tumors showed intermediate behavior.
采用嗜铬粒蛋白A(CGA)免疫组织化学方法研究了350例结直肠癌中内分泌细胞的发生情况。研究了内分泌肿瘤细胞的激素谱、内分泌分化与其他结直肠上皮细胞谱系存在之间的相关性以及内分泌分化在结直肠癌中的预后相关性。30%的病例中发现CGA阳性肿瘤细胞,其中21%为中度阳性,9.0%为广泛阳性。在CGA阳性肿瘤中,70%还产生神经激素,主要是正常结直肠上皮固有的:55%对胰高血糖素样物质呈免疫反应,20%对5-羟色胺呈免疫反应,10%对生长抑素、PYY和HCG呈免疫反应。未发现结直肠内分泌细胞通常不产生的各种神经激素的免疫反应。CGA阳性肿瘤往往比CGA阴性肿瘤更具侵袭性。特别是,CGA广泛阳性的肿瘤生存期较短,在Dukes C期最为明显。多因素分析显示,CGA广泛阳性是预后不良的独立指标。CGA免疫反应性与黏液产生显著相关,但与柱状细胞标志物分泌成分(SC)的表达无关。黏液产生与SC表达显著相关。CGA阳性但黏液和/或SC阴性的肿瘤预后最差。SC表达是一个相对良好的特征,产生黏液的肿瘤表现为中间行为。