Relationship Between Increased Expression of the Axl/Gas6 Signal Cascade and Prognosis of Patients with Upper Tract Urothelial Carcinoma.
OBJECTIVE
Axl, which is in the TAM family of receptor tyrosine kinases, and its ligand, growth arrest-specific gene 6 (Gas6), have been associated with worse prognoses after the surgical treatment of some types of cancers. We herein investigated the biological significance of the protein expression of Axl and Gas6 on the outcomes of patients with upper tract urothelial carcinoma (UTUC).


METHODS
The protein expression of Axl and Gas6 was evaluated by immunohistochemistry, and their relationships with clinicopathological features were investigated in surgical specimens obtained from 161 patients who had been surgically treated for UTUC.


RESULTS
Axl labeling was strong in 67 of 161 (42 %) cases, while Gas6 labeling was strong in 72 of 161 (45 %) cases. The strong expression of Axl correlated with that of Gas6. A high pathological stage (p = 0.009), strong expression of Gas6 (p = 0.038), and strong expression of Axl (p = 0.016) were independent factors for predicting worse cancer-specific survival (CSS). In a subgroup analysis of patients with pT < 2 (N = 53), no significant difference in CSS was observed between patients weakly and strongly expressing Axl/Gas6. In contrast, a subgroup analysis of patients with pT ≥ 2 (N = 108) revealed that the expression levels of Axl and Gas6 correlated with CSS.


CONCLUSIONS
The protein expression of Axl and its ligand Gas6 may be a useful indicator for a worse clinical outcome in UTUC patients, especially patients with pT ≥ 2, who underwent radical nephroureterectomy.
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Seiya
S
Hattori
Department of Urology, Keio University School of Medicine, Tokyo, Japan. eiji-k@kb3.so-net.ne.jp.
Eiji
E
Kikuchi
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Takeo
T
Kosaka
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Yasumasa
Y
Miyazaki
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Nobuyuki
N
Tanaka
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Akira
A
Miyajima
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Shuji
S
Mikami
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Mototsugu
M
Oya
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D014571:Urologic Neoplasms / Q000378:metabolism / Q000473:pathology*; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C000722289:AXL protein, human