Limits of Diagnosis and Molecular Markers for Early Detection of Ulcerative Colitis-Associated Colorectal Neoplasia

Abstract

The incidence of colorectal neoplasia has been increasing among patients with long-standing and extensive ulcerative colitis (UC), and therefore surveillance colonoscopy has been widely recommended. However, because UC-associated neoplasia is often difficult to detect endoscopically and to discriminate from inflammatory regenerative epithelium histologically, the efficacy of current surveillance remains unsatisfactory. In order to overcome these difficulties, adjunctive modalities for diagnosing UC-associated neoplasia, chromo- and magnifying endoscopy for endoscopic diagnosis and analysis of p53 alteration for histological diagnosis have been introduced. Furthermore, if it were possible to differentiate UC patients with long-standing and extensive colitis into subgroups with a high and a low risk of neoplasia, it would enable physicians to conduct more intensive surveillance with these modalities for patients at higher risk. Several molecular alterations of nonneoplastic epithelium in UC patients with neoplasia may be promising as markers for identifying individuals with UC at increased risk of neoplasia. We evaluated estrogen receptor (ER) methylation of nonneoplastic colorectal epithelium to clarify whether this epigenetic alteration can contribute to the prediction of increased neoplasia risk in UC patients and demonstrated that the ER methylation level in nonneoplastic epithelium was higher throughout the colorectum in patients with neoplasia than in those without. These results suggest that analysis of ER gene methylation may be potentially useful for identifying individuals at increased risk of neoplasia among patients with long-standing and extensive UC.

High expression of HSP47 in ulcerative colitis-associated carcinomas: proteomic approach

“…Ulcerative colitis features chronic, relapsing, and debilitating idiopathic inflammation of the colon mucosa and submucosa, and patients with long-standing UC are at high risk of neoplastic development. Ulcerative colitisassociated carcinomas are often difficult to detect endoscopically and to discriminate from inflammatory regenerative epithelium (Sada et al, 2004;Fujii et al, 2008); hence, a molecular marker is urgently required. Recently, proteomics for large-scale studies of gene expression at the protein level have been viewed as a promising experimental approach to explore the control of biological processes and pathways (Lawrie et al, 2001;Dundas et al, 2005;Kuruma et al, 2005).…”

A p53 Gene Mutation in Malignant Fibrous Histiocytoma Associated with Bone Infarction

“…For example, malignant fibrous histiocytoma may arise from the draining sinus of chronic osteomyelitis (Saglik et al 2001;Foti et al 2002); skin cancer may arise from large burn scars (Rhim et al 1995;Alconchel et al 1997;Hayashi et al 2003); and colitic cancer may arise from ulcerative colitis (Fujii et al 2008). The rate of p53 gene alteration is high in these malignant degenerations arising under their respective pre-existing condition (Rhim et al 1995;Fujii et al 2008). Based on the assumption by both Mirra and Bahk (Mirra et al 1974(Mirra et al , 1977Bahk et al 2010), reparative tissue in a bone infarct may create the suitable pre-existing condition for these lesions.…”

“…Moreover, immunohistochemical staining of the p53 protein and screening for the p53 mutation using PCR-SSCP are useful in the adjuvant diagnosis of the aforementioned lesions (Fujii et al 2008), if it is difficult to discriminate neoplasia from regenerative tissues in a histological diagnosis. In bone infarct-associated sarcomas, as well as in the aforementioned lesions, it may be difficult to make an accurate pathological diagnosis (i.e., determining whether it is a neoplasia or regenerative tissue) by using a biopsy specimen since some areas in the same lesion show a variety of histological findings, ranging from reparative granulation tissue to high-grade sarcoma.…”

“…It is well known that secondary malignant degeneration arises under pre-existing conditions. For example, malignant fibrous histiocytoma arises from the draining sinus of chronic osteomyelitis (Saglik et al 2001;Foti et al 2002); skin cancer arises from large burn scars (Rhim et al 1995;Alconchel et al 1997;Hayashi et al 2003); and colic cancer is derived from ulcerative colitis (Fujii et al 2008). Some conditions are associated with a p53 gene mutation (Rhim et al 1995;Fujii et al 2008).…”

Pathological Issues of Ulcerative Colitis/Dysplasia

“…In order to improve the prognosis of patients with UC-associated dysplasia/neoplasia, diagnosis at an early or precancerous stage is crucial. Predisposition to colorectal dysplasia/neoplasia in UC is generally considered to depend on 2 risk factors, namely the presence of long-standing disease and extensive colitis (Fujii et al, 2008, as cited in Ekbom, et al, 1990, and Eaden et al, 2001). Thus, colitic cancers are believed to arise through a chronic inflammation-dysplasia-carcinoma sequence, and therefore early detection of precancerous dysplasia is very important for optimizing the prognosis of patients with long-standing UC.…”