In experimental models, mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF in patients with familial adenomatous polyposis and CRC; however, the histological characteristics of human MDF are not discussed extensively in the report. In the present study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories: flat-MDF and protruded-MDF (having the characteristics of both ACF and MDF). 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, flat-MDF and protruded-MDF, respectively). The density of MDF was 0.0082 lesions ⁄ cm 2 . The ACF identified in sporadic CRC patients corresponded to hyperplastic or non-dysplasic lesions. However, MDF identified in these patients corresponded to low-grade dysplasia. In addition, we found that Paneth cell metaplasia and inflammatory cell infiltration were specific histological features of MDF. These histological characteristics are reported to be associated with the development of CRC. Therefore, our results indicate that MDF might represent preneoplastic lesions in human colorectal carcinogenesis. (Cancer Sci 2012; 103: 144-149) A lthough endoscopic screening and removal of adenomas can reduce the incidence of colorectal cancer (CRC), (1) CRC remains one of the most common causes of cancer-related death in developed countries.(2) Recently, the strategy of cancer prevention using non-toxic chemical entities, termed chemoprevention, has attracted much attention. Adenomas have been established as premalignant lesions of CRC and are characterized by the presence of genetic and histological changes; they have thus been used as the efficacy endpoint in chemoprevention trials.(3) However, such an endpoint requires hundreds of subjects and a very long observation period; therefore, more useful surrogate biomarkers are needed.In experiments on colorectal carcinogenesis, the earliest identifiable precursors of malignant lesions are aberrant crypt foci (ACF). ACF were discovered as the earliest microscopic lesions to appear in the colonic mucosa of mice treated with azoxymethane.(4) Since they were initially described, numerous studies of ACF in animal models have demonstrated that ACF are precursors of CRC and have led to their widespread use as surrogate biomarkers of colorectal carcinogenesis.(5-9) Thus, in rodent models, ACF have been established as precursor lesions of CRC. In humans also, ACF have been identified in the colonic mucosa, in vivo, using methylene blue staining.(10,11) Although some researchers have reported a strong correlation between human ACF and the presence both of...
Abstract. Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have recently been recognized as pre-neoplastic lesions in the colon of carcinogen-treated rodents. In the present study, we analyzed the sequential development of ACF and MDF histopathologically in the colon of rats from 5 to 40 weeks after DMH treatment. The numbers of ACF per colon increased over time during the experiment, and were much higher than the number in tumors, while the number of MDF per colon remained unchanged from the early stage (the 5th week after carcinogen exposure), and approximate to those in tumors. The incidence of ACF, which was much higher than that of tumors, also increased gradually in a time-dependent manner. The incidence of MDF, however, was similar to that of tumors and did not change significantly during the whole experiment. No lesion as dysplasia with high-grade (DHG) or adenocarcinoma (AC) were found in any large ACF from the 5th to 40th week histopathologically, whereas all of the large MDF showed DHG or AC features. Even at 5 weeks, MDF showed features of DHG. We classified these into two forms of MDF: flat and protruded MDF. At 40 weeks, the number of flat MDF per colon decreased significantly compared with that at 20 weeks (p<0.05), however, the number of protruded MDF per colon increased (p<0.01), and the percentage of DHG in a protruded MDF lesion decreased but that of AC increased remarkably. In conclusion, MDF may develop into cancer through the so-called 'de novo cancer' pathway.
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal-recessive and neurodegenerative disorder associated with progressive motor impairment and mental deterioration. The diagnosis of PKAN consists of clinical features and magnetic resonance imaging (MRI) evidence of iron accumulation in the brain, as well as evidence of mutations in the pantothenate kinase 2 (PANK2) gene. Typical clinical features of PKAN are motor symptoms including dystonia, involuntary movement, rigidity and dysarthria, as well as psychiatric symptoms such as anxiety, depression, and mental retardation. However, psychosis has not been reported often in cases of PKAN. This patient presented with anxiety, a tendency to startle easily, and rapidly deteriorating memory impairment. T2-weighted MRI of his brain indicated a specific pattern of hyperintensity within a hypointense medial globus pallidus with a mutation in the gene encoding PANK2. Components of the basal ganglia, including the globus pallidus, play a key role in motor symptoms, cognition, affect, and mood. The basal ganglia are also a central factor in the pathogenesis of psychiatric symptoms in schizophrenia. These lesions are able to aggravate various psychotic symptoms, cognitive function impairments, and mood disorders because PKAN is affected by abnormal iron deposition in the globus pallidus and substantia nigra pars reticulata.
Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have recently been recognized as the pre-neoplastic lesions in the colon of carcinogen-treated rodents. In the present study, we analyzed the sequential development of ACF and MDF histopathologically in the colon of rats from 5 to 40 weeks after DMH treatment. The number of ACF per colon increased over time during the experiment, and was much more than the numbers of tumor, while the number of MDF per colon remained unchanged from the early stage (the 5th week after carcinogen exposure), and approximate to that of tumor. The incidence of ACF, which was much higher than that of tumor, also increased gradually in a time-dependent way. The incidence of MDF, however, was similar to that of tumor and did not have significant change during the whole experiment. No the lesion as dysplasia with high-grade (DHG) or adenocarcinoma (AC) was found in any large ACF from the 5th to 40th week histopathologically, whereas all of the large MDF showed DHG or AC. Even at 5 weeks, MDF shows the appearance as DHG. We classified to two forms of MDF, a flat and a protruded MDF. At the 40 weeks, the number of a flat MDF per colon decreased significantly compared with that in the 20 weeks (p<0.05), but number of a protruded MDF per colon increased (p<0.01), and the percentage of DHG in a protruded MDF decreased but that of AC increased remarkably. In conclusion, MDF might develop into cancer through the so-called “de novo cancer” pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4416. doi:1538-7445.AM2012-4416
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.