散发性结直肠癌中的异常隐窝病灶和脆弱组氨酸三联体蛋白。

Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma.

机构信息

Kim Vaiphei, Aruna Rangan, Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, Pin 160012, India.

出版信息

World J Gastrointest Oncol. 2012 Dec 15;4(12):250-8. doi: 10.4251/wjgo.v4.i12.250.

DOI:10.4251/wjgo.v4.i12.250

PMID:23443232

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3581850/

Abstract

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 χ(2) test and γ 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 non-smokers 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.

摘要

目的

描述散发性结直肠癌毗邻黏膜中异常隐窝病灶（ACF）的特征，并评估脆性组氨酸三联体（Fhit）蛋白和 Ki67 的表达。

方法

在 75 例切除标本中，肉眼识别和组织学分类 ACF。ACF 分为增生性 ACF（HACF）和发育不良性 ACF（DACF）。通过免疫组织化学研究 ACF、癌和正常结肠黏膜的组织学分组中 Fhit 和 Ki67 的表达，并根据观察到的不同组织学组中染色强度和阳性染色细胞数进行分组。通过 Pearson χ(2)检验和有序数据的γ检验对不同组进行比较。P 值<0.05 被认为具有统计学意义。

结果

男性年龄范围为 40 至 86 岁（平均=43.36），女性为 45 至 70 岁（平均=56）。在非肿瘤性结肠黏膜中均发现 HACF；ACF 呈非连续散在病灶，这支持结肠上皮细胞在肿瘤发生中获得单个病灶单克隆性的假说。24 例（32%）有 DACF，与癌灶相邻。Fhit 表达强度：（1）HACF-40% 表现为强强度，类似于正常，36% 为中度，24% 为弱强度；（2）DACF-强 25%，中度 37.5%，弱 37.5%；（3）癌-阴性 16%，强 43%，中度和弱强度各 28.5%。HACF 和 DACF 的 Fhit 蛋白表达强度有显著差异（P<0.05）。老年患者的肿瘤显示出比年轻患者更强的 Fhit 强度（P=0.036）。素食饮食和不吸烟者显示出更强的 Fhit 强度。晚期肿瘤、非素食饮食和年轻与 Fhit 蛋白缺失相关。Ki67 阳性为 HACF 和 DACF 中的扩展隐窝模式，显示隐窝颈部和表面上皮的延伸。癌显示 Ki67 表达显著增加（P<0.05）。Fhit 蛋白与 Ki67 表达呈负相关。