Quantitative analysis of vascular endothelial growth factor in liver metastases from pancreatic carcinoma as a predictor of chemotherapeutic effect and prognosis.
OBJECTIVE
In pancreatic carcinoma, vascular endothelial growth factor (VEGF) expression at the primary site has been suggested to be a prognostic parameter. We quantitatively analyzed VEGF expression in liver metastases from pancreatic carcinoma and examined the correlation among VEGF expression in liver metastases, clinicopathologic factors, and clinical outcome.


METHODS
The subjects consisted of 23 patients with pancreatic adenocarcinoma who had liver metastases and were treated with S-1 and gemcitabine as the first-line treatment. VEGF expression was quantitated by enzyme immunoassay in biopsy specimens of liver metastases and nontumorous liver tissue, and in plasma. In 10 of the 23 patients, VEGF expression was also quantitated in biopsy specimens of the primary pancreatic tumor. All samples were collected before treatment.


RESULTS
The VEGF level in nontumorous liver tissue was 36.6 +/- 10.0 pg/mg protein versus 376.8 +/- 106.1 pg/mg protein in liver metastases (P = 0.0016). Pretreatment VEGF levels in plasma and in primary pancreatic carcinoma did not correlate with VEGF levels in the corresponding liver metastases. The median VEGF level in liver metastases (138.9 pg/mg protein) was used as the cutoff value between high and low VEGF expression in liver metastases. Patients showing high VEGF expression had a significantly longer progression-free survival and overall survival than patients showing low VEGF expression in liver metastases (P = 0.0219 and P = 0.0074, respectively).


CONCLUSIONS
Evaluation of VEGF levels in liver metastases might be useful in assessing the prognosis of patients with metastatic pancreatic carcinoma who are under systemic chemotherapy.
Tawada
Katsunobu
K
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan. dawadawa927@yahoo.co.jp
Ishihara
Takeshi
T
Kobayashi
Akitoshi
A
Yamaguchi
Taketo
T
Tsuyuguchi
Toshio
T
Matsuyama
Masato
M
Yokosuka
Osamu
O
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D005641:Tegafur / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000378:metabolism; D000093542:Gemcitabine
D004338:Drug Combinations; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine