Identification of a Subset of Stage I Colorectal Cancer Patients With High Recurrence Risk.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Lik Hang Lee, Lindy Davis, Lourdes Ylagan, Angela R Omilian, Kristopher Attwood, Canan Firat, Jinru Shia, Philip B Paty, William G Cance
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 114 Issue 5 Pg. 732-739 (05 09 2022) ISSN: 1460-2105 [Electronic] United States
• PMID: 35094080 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Topics

• Colorectal Neoplasms (pathology)
• Humans
• Immunohistochemistry
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models