Morphological and molecular pathological study of mucin -depleted foci as the preneoplastic lesion for depressed flat type on colon carcinogenesis

粘蛋白耗竭灶(MDF)，由发育不良的隐窝形成，不产生粘蛋白，已在接受致癌物质治疗的啮齿动物的结肠中发现。MDF与结肠癌的发生有关，可作为扁平凹陷型结直肠癌的癌前病变。因此，我们在较大样本量的散发性结直肠癌患者中寻找MDF，以揭示人类MDF的组织学特征。方法：对53例散发性结直肠癌患者的结肠标本进行阿尔辛蓝染色，并检测MDF的存在。在相同的样品中，我们还检查了ACF的存在，并注意到一些MDF具有类似ACF的外观。我们将这些病变定义为“隆起的MDF”，并分析了这些结肠粘膜病变(ACF、MDF和隆起的MDF)的组织学特征。结果：共发现结肠粘膜病变354个、41个和19个，平均复数分别为44个、38.9个和66.9个隐窝(ACF、MDF和隆起MDF)。MDF样病变密度为0.0082个/cm2。散发性结直肠癌患者的ACF对应于增生性或非异型增生病变。MDF和突出型MDF对应于低度不典型增生。我们还发现，潘氏细胞化生和炎性细胞浸润是MDF样病变的特有特征。结论：这是首次在大样本范围内调查散发性结直肠癌患者MDF样病变的密度和组织学特征的报道。MDF和突出型MDF兼具MDF和ACF的形态，可作为较晚期的结直肠癌前病变。

Mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production, have identified in the colon of carcinogen-treated rodents. MDF are correlated with colon carcinogenesis and seemed to serve as precancerous lesion of flat-depressed colorectal cancer (CRC). We have, therefore, searched for MDF in sporadic CRC patients in larger sample size to reveal the histological characteristics of human MDF. Methods : Colonic samples from 53 patients of sporadic CRC were stained with Alcian blue and examined the presence of MDF. In the same samples, we also examined the presence of ACF and noticed that some MDF have ACF-like appearance. We defined these lesions as "protruded MDF" and analyzed histological features of these colonic mucosal lesions (ACF, MDF and protruded MDF). Results : We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, MDF and protruded MDF, respectively). The density of MDF like lesions (MDF and protruded MDF) was 0.0082 lesions/cm^2. ACF from sporadic CRC patients were corresponding to hyperplastic or nondysplasic lesions. On the other hand, MDF and protruded MDF were corresponding to low grade of dysplasia. We also found that Paneth cell metaplasia and infiltration of inflammatory cells were specific feature of MDF like lesions. Conclusions : This is the first report that investigating density and histological features of MDF like lesions from sporadic CRC patients in large sample size. MDF and protruded MDF which having both MDF and ACF appearance were suggested to serve as more advanced preneoplastic lesions in human colorectal carcinogenesis.