Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma
Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma
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DOI：
10.4251/wjgo.v4.i12.250
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发表时间：
2012-12-15
影响因子：
3
通讯作者：
Singh, Rajinder
中科院分区：
文献类型：
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作者：
Vaiphei, Kim;Rangan, Aruna;Singh, Rajinder
目的：目的：探讨散发性结直肠癌中异常隐窝病灶（ACF）的特点，并检测其脆性组氨酸三联体（Fhit）蛋白和Ki-67的表达。ACF分为增生型ACF（hyperplastic ACF，HACF）和发育不良型ACF（dysplastic ACF，DACF）。采用免疫组化法检测ACF、癌组织和正常结肠黏膜组织中Fhit和Ki 67的表达，并根据不同组织学类型中Fhit和Ki 67的表达强度和阳性细胞数进行分组。采用Pearson’s评分法进行组间比较。对有序数据进行卡方检验和伽玛检验。结果：男性年龄40 ~ 86岁，平均43.36岁，女性年龄45 ~ 70岁，平均56岁。在非肿瘤性结肠粘膜中研究的所有病例中均发现了HACF;观察到ACF为非连续散在病灶，这支持了结肠上皮细胞在肿瘤生成中获得单病灶单克隆性的假设。24例（32%）有DACF，观察到癌灶闭合。Fhit表达强度：（1）HACF-40%表现出强强度，与正常相似，36%为中等强度，24%为弱强度;（2）DACF -25%为强强度，37.5%为中等强度，37.5%为弱强度;（3）癌阴性，16%为强强度，43%为强强度，28.5%为中等强度和弱强度。Fhit蛋白在HACF和DACF中的表达强度差异有统计学意义（P < 0.05）。与年轻患者相比，老年患者的肿瘤显示出更强的Fhit强度（P = 0.036）。素食者和不吸烟者的Fhit强度更强。晚期肿瘤，非素食饮食和年轻与Fhit蛋白的丢失相关。Ki 67阳性在HACF和DACF中表现为扩展的隐窝模式，扩展到隐窝的颈部区域和表面上皮。癌组织中Ki 67表达明显增高（P < 0.05）。结论：吸烟、非素食、Ki 67表达增加与Fhit蛋白表达强度降低有关。Fhit蛋白表达的缺失可能受到吸烟和非素食饮食等环境因素的影响。(C)2012年百世登。All rights reserved.
AIM: To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67.METHODS: ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson's. chi(2) test and gamma test for the ordinal data. P value < 0.05 was considered as significant.RESULTS: Age range was 40 to 86 years in males (mean = 43.36) and 45 to 70 years in females (mean = 56). HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32%) had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression: (1) HACF -40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2) DACF - strong in 25%, moderate in 37.5% and weak in 37.5%; and (3) carcinoma - negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05). Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036). Vegetarian diet intake and nonsmokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05). Fhit protein had an inverse association with Ki67 expression.CONCLUSION: Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake. (C) 2012 Baishideng. All rights reserved.