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溃疡性结肠炎与结直肠癌:DNA 谱、层粘连蛋白-5γ2 链及细胞周期蛋白 A 表达作为风险评估的早期标志物

Ulcerative colitis and colorectal carcinoma: DNA-profile, laminin-5 gamma2 chain and cyclin A expression as early markers for risk assessment.

作者信息

Habermann J, Lenander C, Roblick U J, Krüger S, Ludwig D, Alaiya A, Freitag S, Dümbgen L, Bruch H P, Stange E, Salo S, Tryggvason K, Auer G, Schimmelpenning H

机构信息

Dept. of Oncology and Pathology, Karolinska Hospital, Stockholm, Sweden.

出版信息

Scand J Gastroenterol. 2001 Jul;36(7):751-8. doi: 10.1080/003655201300192021.

DOI:10.1080/003655201300192021
PMID:11444475
Abstract

BACKGROUND

Ulcerative colitis patients are at increased risk for developing colorectal carcinomas. Despite expensive surveillance programmes, clinical practice reflects an uncertainty in individual risk assessment. The aim of the study was to evaluate independent cellular features with possible predictive value.

METHODS

Two patient groups were selected: group A comprised 8 patients with ulcerative colitis-associated colorectal carcinomas, group B comprised 16 ulcerative colitis patients with risk factors (duration of disease, extent of inflammation, epithelial dysplasias). A total of 683 paraffin-embedded mucosal biopsies were retrospectively evaluated for inflammatory activity, grade of dysplasia, ploidy status, laminin-5 gamma2 chain and cyclin A expression.

RESULTS

Mild or moderate inflammatory activity was present in 78% of all biopsies, low- or high-grade dysplasia in 5.5%. There was no difference in inflammatory activity and dysplasia between patient groups. In group A, 75% of the biopsies exhibited aneuploid DNA distribution patterns. Group B showed mainly proliferative-diploid cell populations (85% / P = 0.006). Laminin-5 gamma2 chain was expressed in 13% of all biopsies, with a higher frequency in group A (P = 0.002). Cyclin A expression was found in 98% of all biopsies, with a higher number of immunopositive cells in group A biopsies (P = 0.014).

CONCLUSIONS

Combined nuclear DNA assessment, laminin-5 gamma2 chain and cyclin A expression may help to identify ulcerative colitis patients with an increased risk for cancer development.

摘要

背景

溃疡性结肠炎患者患结直肠癌的风险增加。尽管有昂贵的监测计划,但临床实践中个体风险评估仍存在不确定性。本研究的目的是评估具有可能预测价值的独立细胞特征。

方法

选择两组患者:A组包括8例溃疡性结肠炎相关结直肠癌患者,B组包括16例有危险因素(病程、炎症程度、上皮发育异常)的溃疡性结肠炎患者。对总共683份石蜡包埋的黏膜活检标本进行回顾性评估,分析炎症活性、发育异常分级、倍体状态、层粘连蛋白-5γ2链和细胞周期蛋白A的表达情况。

结果

所有活检标本中78%存在轻度或中度炎症活性,5.5%存在低级别或高级别发育异常。两组患者在炎症活性和发育异常方面无差异。A组中75%的活检标本显示非整倍体DNA分布模式。B组主要表现为增殖性二倍体细胞群(85% / P = 0.006)。13%的所有活检标本表达层粘连蛋白-5γ2链,A组表达频率更高(P = 0.002)。98%的所有活检标本发现有细胞周期蛋白A表达,A组活检标本中免疫阳性细胞数量更多(P = 0.014)。

结论

联合核DNA评估、层粘连蛋白-5γ2链和细胞周期蛋白A表达可能有助于识别患癌风险增加的溃疡性结肠炎患者。

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