Expression and prognostic significance of Src family members in renal clear cell carcinoma.
BACKGROUND
The aim of this study was to determine whether Src family kinases (SFK) are expressed in renal cell cancer and to assess their prognostic significance.


METHODS
mRNA expression levels were investigated for the 8 SFK members by quantitative real-time PCR in 19 clear cell cancer tissue samples. Immunohistochemical staining was utilised to assess expression of Src kinase, dephosphorylated Src kinase at Y(530) (SrcY(530)), phosphorylated Src at Y(419) (SrcY(419)) and the downstream focal adhesion kinase (FAK) marker at the Y(861) site (FAK Y(861)) in a cohort of 57 clear cell renal cancer specimens. Expression was assessed using the weighted histoscore method.


RESULTS
Src, Lyn, Hck, Fgr and Fyn were the most highly expressed in renal cancer. All members were more highly expressed in T2 disease, and furthermore expression levels between T2 and T3 disease showed a significant decrease for Lck, Lyn, Fyn, Blk and Yes (P=0.032). Assessment of membrane, cytoplasm and nuclear expression of Src kinase, SrcY(530) and SrcY(419) were not significantly associated with cancer-specific survival. High expression of cytoplasmic FAK Y(861) was associated with decreased cancer-specific survival (P=0.001). On multivariate analysis, cytoplasmic FAK Y(861) was independently associated with cancer-specific survival (hazard ratio 3.35, 95% CI 1.40-7.98, P=0.006).


CONCLUSIONS
We have reported that all SFK members are expressed in renal cell carcinoma. The SFK members had their highest levels of expression before the disease no longer being organ confined. We hypothesise that these SFK members are upregulated before the cancer spreading out-with the organ and given that Src itself is not associated with cancer-specific survival but the presence of FAK Y(861), a downstream marker for SFK member activity is associated with decreased cancer-specific survival, we hypothesise that another SFK member is associated with decreased cancer-specific survival in renal cell cancer.
Unit of Experimental Therapeutics, Institute of Cancer, College of MVLS, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK. tahir1@doctors.org.uk
T
T
Qayyum
P A
PA
McArdle
G W
GW
Lamb
F
F
Jordan
C
C
Orange
M
M
Seywright
P G
PG
Horgan
R J
RJ
Jones
G
G
Oades
M A
MA
Aitchison
J
J
Edwards
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019061:src-Family Kinases / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D019061:src-Family Kinases