The constellation of molecular and locoregional changes triggered by long-term exposure of a field of tissue to a carcinogen or regional insult that leaves an entire field susceptible to premalignant (dysplastic), non-invasive (in situ) and eventually, invasive malignancy. The field effect occurs in most tissues and has been well studied in the upper respiratory tract where it is linked to tobacco exposure.
field cancerisation of skin image
Two Paths for UV-Induced Squamous Cell Carcinoma of skin
• Accepted pathway Exposure to UV light triggers cancer-causing mutations in basal keratinocytes, e.g., TP53 mutations often occur in precancerous keratinocyte-derived lesions (actinic keratoses—AKs). With additional mutations–e.g., in NOTCH1 and NOTCH2, AKs progress to squamous cell carcinoma (SCC).
• Proposed (Hu et al) pathway UV light inactivates the Notch pathway in dermal fibroblasts through epigenetic mechanisms, leading cells to acquire a cancer-activated fibroblast (CAF)-like state with reduced elastin and collagen production and increased production of fibroblast growth factors, extracellular matrix proteins, and proteases, triggering proliferation of the overlying epidermal keratinocytes. Regions of epidermal proliferation become progressively enriched with CD45-positive inflammatory cells, which contribute to keratinocyte proliferation and the emergence of AKs that can progress to SCC. The concept of a field effect originated in 1953 with Slaughter et al (Cancer 1953; 6:963–968) who observed multiple primary oral squamous cell carcinomas and their local recurrences in the same field. The molecular mechanism for this effect is unknown; some workers have postulated hypermethylation is one of the triggers that eventually leads to cancer.
Synonyms Field cancerization, field carcinogenesis, field defect, field effect
Reference Cell Volume 149, Issue 6, p1179–1181, 8 June 2012