Clinical implications and utility of field cancerization

Abstract

Cancer begins with multiple cumulative epigenetic and genetic alterations that sequencially transform a cell, or a group of cells in a particular organ. The early genetic events might lead to clonal expansion of pre-neoplastic daughter cells in a particular tumor field. Subsequent genomic changes in some of these cells drive them towards the malignant phenotype. These transformed cells are diagnosed histopathologically as cancers owing to changes in cell morphology. Conceivably, a population of daughter cells with early genetic changes (without histopathology) remain in the organ, demonstrating the concept of field cancerization. With present technological advancement, including laser capture microdisection and high-throughput genomic technologies, carefully designed studies using appropriate control tissue will enable identification of important molecular signatures in these genetically transformed but histologically normal cells. Such tumorspecific biomarkers should have excellent clinical utility. This review examines the concept of field cancerization in several cancers and its possible utility in four areas of oncology; risk assessment, early cancer detection, monitoring of tumor progression and definition of tumor margins.

Correlation of telomere length shortening with promoter methylation profile of p16/Rb and p53/p21 pathways in breast cancer

“…This seriously complicates the use of histologically normal tissue as control. 35,36 Also examining whole tissue sections rather than examining telomere lengths by in-situ methodology, which permits distinction of lesional tissue from contaminating normal tissues is one of the limitations of used methodology. 37 To reduce the challenge of contaminating normal tissues, the paired normal samples in our study were selected with distances more than 1.5 cm to the adjacent tumor tissues.…”

Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization

“…Alternatively, the tumor could influence the surrounding tissue, or it may reflect a combination of these two scenarios. While the underlying mechanisms of field cancerization remain unclear, its occurrence has been described in several epithelial cell derived tumors, including but not limited to lung, esophageal, colorectal, breast and skin cancers (1,4,5). In contrast, relatively little is known about field cancerization in prostate cancer, perhaps due to its previously reported multifocal nature (5,6).…”

“…Field cancerization is of clinical importance (5). In prostate cancer, markers of field cancerization may be important for confirming or detecting disease in biopsies after abnormal prostate-specific antigen (PSA) and/or digital rectal examination (DRE), the current standard of care for detecting prostate cancer.…”

“…While the underlying mechanisms of field cancerization remain unclear, its occurrence has been described in several epithelial cell derived tumors, including but not limited to lung, esophageal, colorectal, breast and skin cancers (1,4,5). In contrast, relatively little is known about field cancerization in prostate cancer, perhaps due to its previously reported multifocal nature (5,6). In addition, prostate cancer is often present in the setting of other benign prostatic conditions, most frequently benign prostatic hyperplasia (BPH), which could influence adjacent cells and thus affect the characterization of field cancerized tissue.…”

“…Therefore, biomarkers that are indicative of disease, yet independent of cancerous histology, i.e. present in field cancerized TAHN tissue, could greatly increase the accuracy of early prostate cancer detection in biopsies (5).…”