Shpitz B, Bomstein Y, Shalev M, Liverant S, Kaufman Z, Klein E, Mekori Y, Bernheim J
Department of Surgery B, Meir General Hospital, Sapir Medical Center, Kfar Sava, Israel.
Anticancer Res. 1999 Jul-Aug;19(4B):3361-6.
Genetic aberrations observed in the large bowel during the neoplastic progression have a cumulative effect and are responsible for the propagation of the multistep malignant process. In the present study we evaluated the immunoreactivity of c-fos, ras, bcl-2 and p53 in aberrant crypt foci (ACF) and minute polyps of the large bowel obtained from patients with colorectal cancer.
ACF and minute polyps were collected from macroscopically normal colonic mucosa. Protein immunoreactivity was detected on parafin sections utilizing the biotin-streptavidin method on 25 hyperplastic, 10 dysplastic ACF, 5 hyperplastic and 10 dysplastic adenomas.
41% of the lesions displayed positive ras immunoreactivity. bcl-2 immunoreactivity was positive in six minute polyps of which five were neoplastic. fos immunoreactivity was detected in five ACF and seven minute polyps, mainly in dysplastic lesions. Two neoplastic polyps were positive for p53 immunoreactivity. Coexpression of two or more oncoproteins was found with increasing frequency in dysplastic versus hyperplastic lesions and in polypoid lesions versus ACF.
Abnormal expression and coexpression in oncoproteins can be identified in the earliest stages of colorectal tumorigenesis and may contribute to the progression of selected lesions during ACF-adenoma-carcinoma sequence.
在肿瘤进展过程中,大肠中观察到的基因畸变具有累积效应,并是多步骤恶性过程传播的原因。在本研究中,我们评估了c-fos、ras、bcl-2和p53在从结直肠癌患者获得的大肠异常隐窝病灶(ACF)和微小息肉中的免疫反应性。
从宏观正常的结肠黏膜中收集ACF和微小息肉。利用生物素-链霉亲和素方法在石蜡切片上检测25个增生性、10个发育异常的ACF、5个增生性和10个发育异常的腺瘤中的蛋白质免疫反应性。
41%的病变显示ras免疫反应性阳性。bcl-2免疫反应性在6个微小息肉中呈阳性,其中5个为肿瘤性。在5个ACF和7个微小息肉中检测到fos免疫反应性,主要在发育异常的病变中。2个肿瘤性息肉p53免疫反应性呈阳性。与增生性病变相比,发育异常病变以及与ACF相比,息肉样病变中两种或更多种癌蛋白的共表达频率增加。
在结直肠癌发生的最早阶段可识别癌蛋白的异常表达和共表达,并且可能在ACF-腺瘤-癌序列中促进某些病变的进展。