Ramírez-Ramírez Miguel Angel, Sobrino-Cossío Sergio, de la Mora-Levy José Guillermo, Hernández-Guerrero Angélica, Macedo-Reyes Verónica de Jesús, Maldonado-Martínez Héctor Aquiles, Alonso-Larraga Juan Octavio, Ramírez-Solis Mauro Eduardo
Department of Gastrointestinal Endoscopy, Instituto Nacional de Cancerología (INCan), México City, Mexico.
J Gastrointest Cancer. 2012 Jun;43(2):209-14. doi: 10.1007/s12029-011-9303-z.
The aims of this study are to characterize the frequency, density, and distribution of aberrant crypt foci (ACF) and its histological features and to determine the frequency of loss of expression of DNA mismatch repair (MMR) proteins of subjects with hereditary nonpolyposic colorectal cancer (HNPCC) and sporadic colon rectal cancer (CRC).
Patients with HNPCC, first-degree relatives of subjects with HNPCC, sporadic CRC, and average risk subjects of sporadic CRC were included prospectively. Total colonoscopy with chromoendoscopy using methylene blue 0.5% and magnification in the right colon (cecum and 20 cm of the ascending colon) and in the left colon (rectum) was performed; loss of expression of MLH1 and MSH2 was evaluated by immunohistochemistry in confirmed ACF.
Fifty-two subjects were included. Thirty-eight of the 119 ACF detected by endoscopy were biopsied. In 14 of the 38 specimens (36.8%), ACF were confirmed by histology (Cohen's kappa, 0.44). In subjects with HNPCC, ACF were identified more frequently in the right segment of the colon than in the left (73.1% vs. 26%); in contrast, ACF predominated in the left segment of the colon (89.3% vs. 10.6%) in subjects with sporadic CRC. There was a loss of MLH1 expression in ACF in subjects with HNPCC.
In HNPCC, we found a greater density of ACF in the right colon, and in sporadic CRC, greater density in the left. ACF present loss in the expression of DNA MMR protein and can be used as an early marker in patients with a risk of HNPCC in whom carcinogenesis appears to be accelerated.
本研究旨在描述异常隐窝灶（ACF）的频率、密度和分布及其组织学特征，并确定遗传性非息肉病性结直肠癌（HNPCC）和散发性结直肠癌（CRC）患者DNA错配修复（MMR）蛋白表达缺失的频率。
前瞻性纳入HNPCC患者、HNPCC患者的一级亲属、散发性CRC患者以及散发性CRC的平均风险受试者。使用0.5%亚甲蓝进行染色内镜检查并在右半结肠（盲肠和升结肠20 cm）和左半结肠（直肠）进行放大的全结肠镜检查；通过免疫组织化学评估确诊的ACF中MLH1和MSH2的表达缺失情况。
共纳入52名受试者。内镜检查发现的119个ACF中有38个进行了活检。在38个标本中的14个（36.8%）中，ACF经组织学证实（Cohen's kappa系数为0.44）。在HNPCC患者中，ACF在结肠右段的发现频率高于左段（73.1%对26%）；相反，在散发性CRC患者中，ACF在结肠左段占主导（89.3%对10.6%）。HNPCC患者的ACF中存在MLH1表达缺失。
在HNPCC中，我们发现右半结肠ACF密度更高，而在散发性CRC中，左半结肠密度更高。ACF存在DNA错配修复蛋白表达缺失，可作为HNPCC风险患者的早期标志物，这类患者的致癌过程似乎加速。
