Wiltz O, O'Hara C J, Steele G D, Mercurio A M
Department of Surgery, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts.
Gastroenterology. 1991 May;100(5 Pt 1):1266-78.
Adenocarcinoma of the colon is one of the most prevalent and lethal of all human malignancies. The early diagnosis and management of this disease could be improved if biological markers, whose expression was restricted to malignant colon cells, were identified. Sucrase-isomaltase is a glycoprotein hydrolase expressed throughout the small intestine and fetal colon but not in the normal adult colon. This study shows that the expression of enzymatically active sucrase-isomaltase is a ubiquitous property of primary and metastatic colon adenocarcinoma. Significant sucrase enzyme activity (i.e., greater than 5 mU/mg protein) was observed in 16 colon carcinomas but not in adjacent normal colon mucosa. Sucrase-isomaltase messenger RNA was identified in all tumors using reverse transcriptase polymerase chain reaction. Using a quantitative polymerase chain reaction analysis, this study shows that the amount of sucrase-isomaltase messenger RNA in tumors examined (3.4 x 10(-8) to 3.19 x 10(-7) micrograms/micrograms total RNA) was greater than in adjacent mucosa (0 to 3.4 x 10(-8) micrograms/micrograms total RNA). This induction of sucrase-isomaltase messenger RNA and enzyme activity was corroborated by immunostaining. Of 30 colon adenocarcinomas examined, 80% were positive for sucrase-isomaltase. In addition, all colon carcinoma metastases examined were positive for sucrase-isomaltase. The staining pattern was distinct and demarcated tumor cells from the surrounding histologically normal tissue. No sucrase-isomaltase staining was seen in normal mucosa from the same patients. With the exception of lung, no sucrase-isomaltase immunostaining was observed in a variety of examined noncolonic adenocarcinomas. Thus, the specificity and ubiquity of sucrase-isomaltase expression in adenocarcinomas of the colon can be exploited to improve the clinical management of this disease. In addition, studies on the structure of the sucrase-isomaltase gene and its regulatory elements should contribute toward understanding the alteration of gene expression by oncogenic transformation of the colonic mucosa.
结肠腺癌是人类最常见且致命的恶性肿瘤之一。如果能鉴定出其表达仅限于恶性结肠细胞的生物标志物,那么这种疾病的早期诊断和治疗有望得到改善。蔗糖酶 - 异麦芽糖酶是一种糖蛋白水解酶,在整个小肠和胎儿结肠中表达,但在正常成人结肠中不表达。本研究表明,具有酶活性的蔗糖酶 - 异麦芽糖酶的表达是原发性和转移性结肠腺癌的普遍特征。在16例结肠癌中观察到显著的蔗糖酶活性(即大于5 mU/mg蛋白质),而在相邻的正常结肠黏膜中未观察到。使用逆转录聚合酶链反应在所有肿瘤中鉴定出蔗糖酶 - 异麦芽糖酶信使核糖核酸。通过定量聚合酶链反应分析,本研究表明,所检测肿瘤中蔗糖酶 - 异麦芽糖酶信使核糖核酸的量(3.4×10⁻⁸至3.19×10⁻⁷微克/微克总RNA)高于相邻黏膜(0至3.4×10⁻⁸微克/微克总RNA)。免疫染色证实了蔗糖酶 - 异麦芽糖酶信使核糖核酸和酶活性的这种诱导。在所检查的30例结肠腺癌中,80%的蔗糖酶 - 异麦芽糖酶呈阳性。此外,所检查的所有结肠癌转移灶的蔗糖酶 - 异麦芽糖酶均呈阳性。染色模式明显,将肿瘤细胞与周围组织学正常的组织区分开来。在同一患者的正常黏膜中未观察到蔗糖酶 - 异麦芽糖酶染色。除肺部外,在各种检查的非结肠腺癌中未观察到蔗糖酶 - 异麦芽糖酶免疫染色。因此,蔗糖酶 - 异麦芽糖酶在结肠腺癌中表达的特异性和普遍性可用于改善这种疾病的临床管理。此外,对蔗糖酶 - 异麦芽糖酶基因结构及其调控元件的研究应有助于理解结肠黏膜致癌转化导致的基因表达改变。