The chronic inflammatory bowel disease ulcerative colitis (UC) occurs commonly in the US and other Western countries, but its etiology is unknown. An association between UC and an elevated risk for colorectal cancer is well established. UC-associated colorectal carcinogenesis is probably driven by chronic inflammation, but the mechanism is unclear. The morphological development of UC-associated cancer differs from that of its sporadic counterpart. Similarly, detailed molecular analyses have indicated that whereas many of the genetic alterations observed in sporadic colon cancers also occur in UC-associated neoplasms, the timing and frequency of those changes in the setting of UC are different. These histological and molecular signatures may very well be reflective of an inflammation-driven carcinogenesis process in UC patients. Studies in animal models of UC have helped to shed light on the mechanisms of inflammation-driven colorectal carcinogenesis. The available evidence suggests that DNA damage caused by oxidative stress in the characteristic damage-regeneration cycle is a major contributor to colorectal cancer development in UC patients. Based on this concept, iron over-nutrition is proposed as a risk factor and dietary antioxidants as protective factors for UC and associated carcinogenesis.

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Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models.

The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applications as prognostic variables.

Flow cytometric study has been used to measure the cellular DNA content of solid tumors for the last decade, and of paraffin-embedded tumor specimens for the last 5 years. Ploidy and proliferative activity are the two properties commonly measured by DNA content flow cytometric study. The ability to study archival, paraffin-embedded tumors has hastened an appreciation of the prognostic utility of this assay. Either abnormal ploidy or elevated proliferative activity predict a worsened disease-free or overall survival in most common adult malignancies. Both abnormalities are associated with poor outcome in locoregional breast, non-small cell lung, and colorectal cancers, and in all stages of ovarian cancer. Abnormal ploidy is also a dire prognostic indicator for cancers arising from the kidney, bladder, prostate, and endometrium. Clinical management of patients with these diseases may be aided by studying their tumors for these objective markers of biological aggressiveness.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819900301%2965%3A5%3C1194%3A%3AAID-CNCR2820650528%3E3.0.CO%3B2-M

Ploidy, proliferative activity and prognosis. DNA flow cytometry of solid tumors

Barrett's esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma.

The use of flow cytometry to analyze the cellular DNA content of human malignancies has become increasingly commonplace. The relationship between abnormalities in DNA content or proliferative characteristics and prognosis is becoming clear for a variety of malignancies in part through new techniques that permit analysis of archival material. High- and low-risk groups of patients with early breast and bladder carcinomas, non-small-cell lung cancer, and colorectal, ovarian, and cervical carcinoma can be distinguished on the basis of abnormal stemline DNA content. In several hematologic and common pediatric malignancies, the prognostic relevance of DNA content flow cytometry has been similarly established. Though the interpretation of tumor cell cycle analyses is less certain, this characteristic may also be prognostically important. However, generalizations cannot be made when applying flow cytometric DNA analysis to clinical decision making. The prognostic importance of an abnormal DNA histogram for an individual patient must be assessed on the basis of the relevant data base for that particular tumor type. The current extent of this data base for various malignancies is reviewed.

Flow cytometry, cellular DNA content, and prognosis in human malignancy.

The cellular DNA content in colorectal biopsies from 51 patients with chronic ulcerative colitis has been studied with flow-cytometric technique. The DNA pattern has been related to the duration of the disease, and to histopathology. Aneuploid cell lines were found in eight patients, two of which had histopathologically verified malignancies. Aneuploid cell lines were found in 2% of biopsies from mucosa classified as normal, in 10% of biopsies with inflammation, hyperplasia or atrophy, in 25% of polyps and in biopsies with dysplasia and in seven of eight biopsies from adenocarcinomas. Four of 27 cases with 11 to 20 years duration of disease, and 4 of 10 with more than 20 years disease, had aneuploid cell lines. Combined with colonoscopy the flow-cytometric technique can routinely be used in the follow-up of patients with ulcerative colitis in screening for malignant cell lines.

Cary Hammarberg

Papers

Early detection of malignancy in ulcerative colitis. A flow-cytometric DNA study.