Abstract
Prior to the development of a localized cancerous tumor, diffuse molecular, and structural alterations occur throughout an organ due to genetic, environmental, and lifestyle factors. This process is known as field carcinogenesis. In this study, we used partial wave spectroscopic (PWS) microscopy to explore the progression of field carcinogenesis by measuring samples collected from 190 patients with a range of colonic history (no history, low‐risk history, and high‐risk history) and current colon health (healthy, nondiminutive adenomas (NDA; ≥5 mm and <10 mm), and advanced adenoma [AA; ≥10 mm, HGD, or >25% villous features]). The low‐risk history groups include patients with a history of NDA. The high‐risk history groups include patients with either a history of AA or colorectal cancer (CRC). PWS is a nanoscale‐sensitive imaging technique which measures the organization of intracellular structure. Previous studies have shown that PWS is sensitive to changes in the higher‐order (20–200 nm) chromatin topology that occur due to field carcinogenesis within histologically normal cells. The results of this study show that these nanoscale structural alterations are correlated with a patient's colonic history, which suggests that PWS can detect altered field carcinogenic signatures even in patients with negative colonoscopies. Furthermore, we developed a model to calculate the 5‐year risk of developing CRC for each patient group. We found that our data fit this model remarkably well (R 2 = 0.946). This correlation suggests that PWS could potentially be used to monitor CRC progression less invasively and in patients without adenomas, which opens PWS to many potential cancer care applications.
Highlights
Field carcinogenesis, first conceptualized by Slaughter et al [1], is the concept that diffuse molecular and structural alterations exist in healthy tissue prior to the development of a localized tumor
Pairing this meta-analysis with partial wave spectroscopic (PWS) measurements, we explore the progression of nanoscopic alterations in chromatin during field carcinogenesis by measuring samples collected from patients with a range of colonic history and current colon health
We show that PWS microscopy is sensitive to the severity of a patient’s colonic history and that nanoscale alterations in chromatin strongly correlate with colorectal cancer (CRC) risk
Summary
First conceptualized by Slaughter et al [1], is the concept that diffuse molecular and structural alterations exist in healthy tissue prior to the development of a localized tumor. Cellular exposure to these factors is not always limited to a specific location, but can affect large areas of the body (i.e., smoking increases the risk of lung, bladder, pancreatic, and colorectal cancer) This leads to an important facet of field carcinogenesis: The field is not localized to the tumor site, but can occur across an entire organ, multiple organs, or even the whole body [2]. Even without chronic exposure to a known carcinogenic agent, studies of field carcinogenesis for colorectal cancer (CRC) have identified biomarkers obtained from the visually normal rectal mucosa showing cellular and molecular changes, such as increased apoptotic resistance [8], increased cell proliferation [9], changed gene expression [10], and modified patterns of protein expression [11] Identification of these field biomarkers, such as rectal apoptosis rate measured from normal rectal mucosa, has been shown to be predictive of future adenoma development and could potentially be used to identify high-risk patients [12]
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