Identification of Mucin Depleted Foci in the Human Colon
Identification of Mucin Depleted Foci in the Human Colon
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DOI：
10.1158/1940-6207.capr-08-0125
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发表时间：
2008-12-01
影响因子：
3.3
通讯作者：
Caderni, Giovanna
中科院分区：
文献类型：
--
作者：
Femia, Angelo Pietro;Giannini, Augusto;Caderni, Giovanna
异常隐窝病灶(ACF)最初是在用结肠癌特异性致癌物治疗的啮齿动物中发现的，在结肠癌(CRC)高危人群中也被发现，并被广泛用作癌症生物标记物。然而，记录ACF异质性的研究质疑了它们的癌前性质。最近，我们描述了用结肠特异性致癌物治疗的大鼠结肠中粘蛋白耗竭的发育不良灶(MDF)。与结肠肿瘤一样，MDFS显示Wnt信号的激活是由β-连环素基因和APC基因突变驱动的，APC是结直肠癌发生的关键基因。因为到目前为止只在啮齿类动物中发现了MDFS，所以我们想在人类中寻找类似的病变。家族性腺瘤性息肉病(FAP)患者携带APC基因的胚系突变，是结直肠癌的高危人群。因此，我们首先在FAP患者的未切片结肠样本中搜索MDF样病变，然后在散发性CRC患者中搜索MDF样病变。在FAP患者的结肠中存在MDF(平均0.0577个病变/cm(2))，而在结直肠癌患者中MDF的密度要低得多(平均0.0006个病变/cm(2))。所有患者均观察到ACF的变化。在FAP和CRC中发现的所有MDF的组织学准备包括不同级别的不典型增生的微腺瘤。在高危患者中出现的MDF样病变提供了证据，表明这些病变在人类病理学中具有对应性，并且正如在啮齿动物中观察到的那样，可能代表了结直肠癌的早期阶段。
Aberrant crypt foci (ACF) originally described in rodents treated with colon-specific carcinogens have been identified also in humans at high risk of colon cancer (CRC) and are extensively used as cancer biomarkers. However, studies documenting the heterogeneity of ACF have questioned their precancerous nature. Recently, we described dysplastic foci depleted of mucins (MDF) in the colon of rats treated with colon-specific carcinogens. Like colon tumors, MDFs show activation of Wnt signaling driven by mutations in the beta-catenin gene and Apc, a key gene in colorectal carcinogenesis. Because MDFs have been identified thus far only in rodents, we wanted to search for similar lesions in humans. Familial adenomatous polyposis (FAP) subjects, carrying germ-line mutations in the APC gene, are at high risk of CRC. Therefore, we first searched for MDF-like lesions in unsectioned colon samples from FAP patients and then in patients with sporadic CRC. MDFs were present in the colon of FAP patients (average of 0.0577 lesions/cm(2)) and at a much lower density in CRC patients (average of 0.0006 lesions/cm(2)). ACFs were also observed in all patients. Histologic preparations of all the MDFs identified in FAP and CRC consisted of microadenomas at variable grades of dysplasia. The occurrence of MDF-like lesions in high-risk patients provides evidence that these lesions have a counterpart in human pathology and, as observed in rodents, may represent the very early stages of CRC.