Nondysplastic Crypts in Fission in Nonpolypoid Adenomas and in the Adjacent Mucosa Support Field Cancerization in the Colon

Rubio, Carlos A.; Schmidt, Peter T.

doi:10.21873/anticanres.14910

Cited by 3 publications

(3 citation statements)

References 44 publications

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“…The progressive accumulation of genetic mutations and DNA methylation changes in normal tissue around tumors lead to the development and progression of adenomas, which might become adenocarcinomas. Such alterations are a result of field cancerization[ 28 ]. Studies have demonstrated that the aberrant methylation of cancer-related genes could serve as epigenetic markers for CRC risk owing to the field of susceptibility[ 29 ], and such findings are consistent with our finding that compared with abnormal DNA methylation in tumor tissue, abnormal DNA methylation in adjacent normal tissue is highly correlated with an unfavorable prognosis after surgical resection.…”

Section: Discussionmentioning

confidence: 99%

Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan

Su¹,

Lai²,

Hu³

et al. 2022

WJG

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BACKGROUND Patients with colorectal cancer (CRC) undergo surgery, as well as perioperative chemoradiation or adjuvant chemotherapy primarily based on the tumor–node– metastasis (TNM) cancer staging system. However, treatment responses and prognostic outcomes of patients within the same stage vary markedly. The potential use of novel biomarkers can improve prognostication and shared decision making before implementation into certain therapies. AIM To investigate whether SUMF2 , ADAMTS5 , and PXDN methylation status could be associated with CRC prognosis. METHODS We conducted a Taiwanese cohort study involving 208 patients with CRC recruited from Tri-Service General Hospital and applied the candidate gene approach to identify three genes involved in oncogenesis pathways. A methylation-specific polymerase chain reaction (MS-PCR) and EpiTYPER DNA methylation analysis were employed to detect methylation status and to quantify the methylation level of candidate genes in tumor tissue and adjacent normal tissue from participants. We evaluated SUMF2 , ADAMTS5 , and PXDN methylation as predictors of prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS), using a Cox regression model and Kaplan–Meier analysis. RESULTS We revealed various outcomes related to methylation and prognosis. Significantly shorter PFS and OS were associated with the CpG_3+CpG_7 hypermethylation of SUMF2 from tumor tissue compared with CpG_3+CpG_7 hypomethylation [hazard ratio (HR) = 2.24, 95% confidence interval (CI) = 1.03-4.85 for PFS, HR = 2.56 and 95%CI = 1.08-6.04 for OS]. By contrast, a significantly longer RFS was associated with CpG_2 and CpG_13 hypermethylation of ADAMTS5 from normal tissue compared with CpG_2 and CpG_13 hypomethylation [HR (95%CI) = 0.15 (0.03-0.71) for CpG_2 and 0.20 (0.04-0.97) for CpG_13]. The relationship between the methylation status of PXDN and the prognosis of CRC did not reach statistical significance. CONCLUSION Our study found that CpG_3+CpG_7 hypermethylation of SUMF2 from tumor tissue was associated with significantly shorter PFS and OS compared with CpG_3+CpG_7 hypomethylation. CpG_2 and CpG_13 hypermethylation of ADAMTS5 from normal tissue was associated with a significantly longer RFS compared with CpG_2 and CpG_13 hypomethylation. These methylation-related biomarkers which have implications for CRC prognosis prediction may aid physicians in clinical decision-making.

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Section: Discussionmentioning

confidence: 99%

Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan

Su¹,

Lai²,

Hu³

et al. 2022

WJG

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“…Inversely, crypt branching was frequently found in the colon mucosa of adult patients having either infectious colitis (24), ulcerative colitis (25), or Crohn's colitis (26). Moreover, crypt branching was also frequent in the nondysplastic colon mucosa adjacent to nonpolypoid adenomas (27). The increase in crypt branching in these instances implies that not only inflammatory insults, but also proximity to mutated neoplastic tissue of nonpolypoid adenomas can unchain crypt replication in the colon mucosa.…”

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confidence: 99%

Further Study on Field Cancerization in the Human Colon

Rubio

Lang-Schwarz

2022

Anticancer Res

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Background/Aim: Nearly 70 years ago, Slaughter launched the hypothesis of field cancerization for oral carcinomas; that hypothesis was subsequently also claimed for carcinomas in other organs. We previously found in the colon mucosa adjacent to nonpolypoid adenomas, branching crypts lined by normal epithelium (BCNE). Here, we explored whether BCNE could also be found in the colon mucosa adjacent to sporadic polypoid tubular adenomas (TA), the most prevalent of all colon adenomas. Patients and Methods: Nondysplastic mucosa adjacent to TA was found in 103 out of 131 TA. All BCNE adjacent to TA were recorded. Results: In 98 (95.1%) out of 103 TA having nondysplastic adjacent mucosa, 645 BCNE were registered: 82.6% were in asymmetric branching and 17.4% in symmetric branching. Thus, BCNE in asymmetric branching predominated. The frequency of BCNE adjacent to TA was influenced by the adenoma size and degree of dysplasia severity. Contrarywise, the frequency of BCNE adjacent to TA was neither influenced by the age or sex of the patients, nor by the colon localization of TA. Conclusion: BCNE often occur in the normal mucosa adjacent to TA. BCNE emerge as integral components of TA. The majority of the BCNE were in asymmetric branching, considered as aberrations of cryptogenesis. We propose that the accretion of asymmetric BCNE adjacent to TA supports Slaughter's hypothesis of field cancerization.

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“…Following a classical histological description of the normal colon mucosa, it has been axiomatic to describe colon crypts as closely aligned glands in parallel, as "test tubes", vertical to the surface epithelium and the muscularis mucosae (1). However, this description applies only to welloriented, upright crypts, often seen in sections from colectomy specimens (6), or mucosectomies (7). In contrast, endoscopic biopsies in normal donors reveal cross-cut crypts in a horizontal (tangential) plane, displaying ring-shaped cross-cut crypts, similar in outline and diameter (8,9).…”

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confidence: 99%

Crypts in Asymmetric Fission in Endoscopic Biopsies from German Patients With Inflammatory Bowel Disease

Rubio

Lang-Schwarz

2021

Anticancer Res

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Background/Aim: We previously found in Swedish patients with inflammatory bowel disease (IBD), crypts in symmetric fission (CSF) and in asymmetric fission (CAF). This study aimed to examine CSF and CAF in a cohort of German patients with IBD. Patients and Methods: H&E-sections from 106 IBD-patients [59 ulcerative colitis (UC) and 47 Crohn colitis (CCs)] were analysed. Results: A total of 588 crypts in fission (CF) were found; 342 (58.2%) in UC and 246 (41.8%) in CCs. Out of the 505 CAFs found, 304 (60.2%) were recorded in UC, and 201(39.8%) in CCs (p=0.15272). Conclusion: Despite that German and Swedish populations reside in disparate geographical regions with different ecological milieus, the proportions of CAF and CSF were similar, thereby suggesting that CAF and CSF develop in IBD independently of the local environmental conditions in the two regions.

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Nondysplastic Crypts in Fission in Nonpolypoid Adenomas and in the Adjacent Mucosa Support Field Cancerization in the Colon

Cited by 3 publications

References 44 publications

Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan

Differential DNA methylation analysis of SUMF2, ADAMTS5, and PXDN provides novel insights into colorectal cancer prognosis prediction in Taiwan

Further Study on Field Cancerization in the Human Colon

Crypts in Asymmetric Fission in Endoscopic Biopsies from German Patients With Inflammatory Bowel Disease

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