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- Title
Identification of a Subset of Stage I Colorectal Cancer Patients With High Recurrence Risk.
- Authors
Lee, Lik Hang; Davis, Lindy; Ylagan, Lourdes; Omilian, Angela R; Attwood, Kristopher; Firat, Canan; Shia, Jinru; Paty, Philip B; Cance, William G
- Abstract
<bold>Background: </bold>A challenge in early-stage colorectal cancer (CRC) is identifying biomarkers that predict an increased risk for recurrence. A potential clinically adaptable biomarker is focal adhesion kinase (FAK), a tyrosine kinase that promotes invasion and metastasis.<bold>Methods: </bold>An initial, single-institution, 298-patient cohort with all stages of CRC and long-term follow-up was assessed for FAK with tissue microarrays using immunohistochemistry. FAK expression was scored and dichotomized into high and low. Subsequently, a validation cohort of 517 early-stage CRCs from a separate institution was evaluated. All statistical tests were 2-sided.<bold>Results: </bold>FAK overexpression did not correlate with any known histologic feature and was an early event in CRC, increasing from normal colon to stage I, and stage I to II, but not different at higher stages. High FAK was associated with decreased 10-year recurrence-free survival (RFS) among stage I patients (70.2% for high FAK vs 94.1% for low, P = .02), but not among higher stages in the initial cohort. The same finding was seen in the validation cohort (73.1% for high FAK vs 93.1% for low, P = .004). Multivariable survival analysis for stage I patients showed only two statistically significant factors predicting RFS: FAK (hazard ratio = 5.27, 95% confidence interval = 1.81 to 15.33, P = .002) and perineural invasion (hazard ratio = 7.38, 95% confidence interval = 1.01 to 53.96, P = .049). FAK was the only statistically significant factor in multivariable analysis across RFS, overall, and disease-specific survivals.<bold>Conclusions: </bold>High FAK expression identified a subset of stage I CRC patients with high incidence of recurrence and reduced survival, suggesting that FAK has important prognostic value. These patients would immediately benefit from more rigorous surveillance protocols for recurrent disease.
- Subjects
IMMUNOHISTOCHEMISTRY; PROGNOSIS; COLORECTAL cancer; TUMOR classification; PROPORTIONAL hazards models
- Publication
JNCI: Journal of the National Cancer Institute, 2022, Vol 114, Issue 5, p732
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djac023