Combined expression of the non-receptor protein tyrosine kinases FAK and Src in primary colorectal cancer is associated with tumor recurrence and metastasis formation.
OBJECTIVE
The protein tyrosine kinase focal adhesion kinase (FAK) and Src in association with phosphorylation of the adapter protein paxillin are essential in tumor metastasis formation. Elevated levels of FAK, Src and paxillin may increase the metastatic potential of colorectal tumor cells. The aim of the current study was to examine the expression of FAK, Src, and paxillin using immunohistochemistry in the context of disease progression and to evaluate its clinical significance as a prognostic factor.


METHODS
The relationship between FAK, Src and paxillin levels and colorectal cancer progression was evaluated by immunohistochemistry in 104 colorectal cancer specimens with clinical follow up. In addition, FAK, Src and paxillin expression levels were quantified in 68 colorectal tumors and corresponding liver metastases.


RESULTS
FAK and paxillin expression individually did not significantly impact time to recurrence (p=0.09, and p=0.89 respectively). Src expression was associated with tumor recurrence p=0.03. However, tumors that expressed both high FAK and Src levels had a significant shorter time to recurrence (p=0.004, hazard ratio: 2.98, 95% CI 1.14-6.31). FAK, Src and paxillin showed equivalent levels in corresponding liver metastases compared to the primary tumors (p=0.67, p=0.28 and p=0.34 respectively).


CONCLUSIONS
These findings show that high levels of FAK and Src combined were predictive for recurrence of colorectal cancer. In addition, expression of FAK, Src and paxillin in colorectal cancer were maintained in corresponding distant metastases.
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
P
P
de Heer
M M
MM
Koudijs
C J H
CJ
van de Velde
R I J M
RI
Aalbers
R A E M
RA
Tollenaar
H
H
Putter
J
J
Morreau
B
B
van de Water
P J K
PJ
Kuppen
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D051419:Paxillin / Q000096:biosynthesis; D011379:Prognosis; D019061:src-Family Kinases / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D051419:Paxillin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases