Watari Jiro, Saitoh Yusuke, Obara Takeshi, Fujiya Mikihiro, Maemoto Atsuo, Ayabe Tokiyoshi, Ashida Toshifumi, Yokota Kinichi, Orii Yutaka, Kohgo Yutaka
Third Department of Internal Medicine, Asahikawa Medical College, Japan.
Am J Gastroenterol. 2002 Aug;97(8):2109-15. doi: 10.1111/j.1572-0241.2002.05931.x.
Serial colonoscopic observations were prospectively conducted to elucidate the natural history of nonpolypoid tumors. Furthermore, to clarify whether cell kinetic status affects the tumor development, proliferative indices, apoptotic indices, and K-ras codon 12 point mutations on biopsy specimens were investigated.
Seventy-five colorectal tumors, 13 polypoid and 62 nonpolypoid type (56 flat elevated and six depressed type) were studied. Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method, respectively. Point mutations at K-ras codon 12 were examined by enriched polymerase chain reaction-based restriction fragment length polymorphism assay.
The average follow-up period was 22 months (range 1-50). The lesions of subsequent exophytic growth, unchanged shape, depressed growth, and disappearance were observed in 0%, 92%, 0%, and 8% of polypoid type, in 39%, 39%, 13%, and 9% of flat elevated type, and in 33%, 67%, 0%, and 0% of depressed type, respectively. There was no significant difference in tumor size between initial and follow-up colonoscopy. Nonpolypoid tumors apparently changed to the exophytic growth during 2 yr or more. The tumors with exophytic growth had significantly higher proliferative indices/apoptotic indices ratios than those with unchanged morphology and disappearance/depressed growth (p < 0.05, respectively). K-ras codon 12 point mutations did not correlate with tumor development.
Cell kinetic status plays an important role in determining minute colorectal tumor development, but not K-ras codon 12 mutations. Minute nonpolypoid adenomas frequently tend to grow slowly, and nearly 40% of those become the exophytic growth with time. Most of minute nonpolypoid tumors seem to follow the adenoma-carcinoma sequence.
前瞻性地进行系列结肠镜观察以阐明非息肉样肿瘤的自然病史。此外，为明确细胞动力学状态是否影响肿瘤发展，对活检标本的增殖指数、凋亡指数及K-ras密码子12点突变进行了研究。
研究了75例结直肠肿瘤，其中13例为息肉样肿瘤，62例为非息肉样肿瘤（56例扁平隆起型和6例凹陷型）。分别用抗Ki-67抗体和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测增殖细胞和凋亡细胞。通过基于富集聚合酶链反应的限制性片段长度多态性分析检测K-ras密码子12的点突变。
平均随访期为22个月（范围1 - 50个月）。息肉样肿瘤后续出现外生性生长、形态不变、凹陷性生长及消失的病变比例分别为0%、92%、0%和8%；扁平隆起型分别为39%、39%、13%和9%；凹陷型分别为33%、67%、0%和0%。初次结肠镜检查与随访时肿瘤大小无显著差异。非息肉样肿瘤在2年或更长时间内明显转变为外生性生长。外生性生长的肿瘤其增殖指数/凋亡指数比值显著高于形态不变及消失/凹陷性生长的肿瘤（分别为p < 0.05）。K-ras密码子12点突变与肿瘤发展无关。
细胞动力学状态在决定微小结直肠肿瘤发展中起重要作用，但与K-ras密码子12突变无关。微小非息肉样腺瘤常倾向于缓慢生长，近40%的此类腺瘤随时间推移会转变为外生性生长。大多数微小非息肉样肿瘤似乎遵循腺瘤 - 癌序列。
