Predictive role of tissue-based molecular markers in patients treated with sunitinib for metastatic renal cell carcinoma.
BACKGROUND
We analyzed the clinicopathological data of patients undergoing radical nephrectomy for clear cell type renal cell carcinoma (RCC) who presented with metastasis and were subsequently treated with sunitinib and identified molecular markers in nephrectomy specimens to predict susceptibility to sunitinib.


METHODS
The medical records of 65 patients who underwent nephrectomy for metastatic clear cell type RCC and were then treated with sunitinib were reviewed. The nephrectomy specimens were subjected to prospective immunohistochemical staining for vascular endothelial growth factor, vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor-B, and platelet-derived growth factor receptor-β expression.


RESULTS
In 58 evaluable patients, the median value of initial and best overall response was -9.69 and -24.04 %, respectively. VEGFR-2 expression was associated significantly with initial and best overall responses to sunitinib, along with Karnofsky performance status and Memorial Sloan-Kettering Cancer Center prognostic risk group. Multiple linear regression analyses revealed that strong VEGFR-2 expression was positively associated with the best reduction in tumor response (β = -0.275, P = 0.016) and poor Karnofsky performance status was negatively associated it (β = 0.477, P < 0.001). Karnofsky performance status and retroperitoneal lymph node involvement associated independently with progression-free- and overall survivals. None of the molecular markers associated significantly with survival.


CONCLUSIONS
VEGFR-2 expression might be a useful biomarker for predicting the response to sunitinib by patients with metastatic RCC. Karnofsky performance status and retroperitoneal lymph node involvement were predictive of disease progression and death.
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 138-736, Korea.
Dalsan
D
You
Sang Hoon
SH
Song
Yong Mee
YM
Cho
Jae-Lyun
JL
Lee
In Gab
IG
Jeong
Cheryn
C
Song
Jun Hyuk
JH
Hong
Choung-Soo
CS
Kim
Hanjong
H
Ahn
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011237:Predictive Value of Tests; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D000077210:Sunitinib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000970:Antineoplastic Agents; D015415:Biomarkers; D007211:Indoles; D020574:Proto-Oncogene Proteins c-sis; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D020797:Receptor, Platelet-Derived Growth Factor beta; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib