Angiogenesis and cathepsin expression are prognostic factors in pancreatic adenocarcinoma after curative resection.
BACKGROUND
Curative resection of pancreatic adenocarcinoma is the only clinical parameter related to a favorable prognosis while other clinicopathological parameters fail. To evaluate whether angiogenesis, vascular endothelial growth factor (VEGF) or certain tumor proteases, e.g., cathepsin B (CTSB) and L (CTSL), are factors of prognostic relevance, we investigated their expression in patients with long- and short-term survival after curative resection (RO) because of pancreatic adenocarcinoma.


METHODS
Twenty-nine tissue samples from patients with adenocarcinoma of the pancreas were examined. The patients were selected in a long-term survival group with a survival > or = 24 mo (n = 18) and a shortterm survival group of patients, who died within 8 mo after surgery because of their malignancy (n = 11). The microvessel quantification was performed immunohistochemically using a monoclonal anti-CD34 antibody. VEGF, CTSB, and CTSL expressions was studied using polyclonal antibodies (PAbs).


RESULTS
The median microvessel density (MVD) was 75 (range 39-182). MVD correlated significantly with the survival time after surgery (p = 0.0132) but not with clinicopathological parameters. In cancer cells, VEGF was positive in 82.8% and showed significant correlation with the MVD (p = 0.0002) and survival time (p = 0.0395). Positive immunoreactivity could be obtained for 96.5% for CTSB and 84.2% for CTSL. Expression of both proteases correlated significantly with the survival time after surgery (CTSB p = 0.0002, CTSL p = 0.0001). Furthermore, CTSB expression correlated with invasion of the perineural space. Thus, a short postoperative survival correlated with a high MVD, and highly expressed VEGF, CTSB, and CTSL. No significant correlation between MVD, VEGF, as well as CTSL and clinicopathological parameters was found. For routinely assessed markers (e.g., TNM-stage, UICC-stage, and so on) no significant correlation with survival time was found in this small group of patients.


CONCLUSIONS
These findings indicate that the MVD, VEGF, CTSB, and CTSL are prognostic factors after curative resection, whereas other parameters (TNM, UICC, and so on) failed to show prognostic relevance in our group of patients. Furthermore, the correlation between MVD and VEGF underlines the importance of this growth factor for angiogenesis and tumor growth. The correlation between CTSB and perineural invasion demonstrates the involvement of cathepsins in local tumor invasion.
Niedergethmann
M
M
Department of Surgery, University-Hospital Mannheim, University of Heidelberg, Germany. marco.niedergethmann@chir.ma.uni-heidelberg.de
Hildenbrand
R
R
Wolf
G
G
Verbeke
C S
CS
Richter
A
A
Post
S
S
D000230:Adenocarcinoma / Q000098:blood supply* / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002403:Cathepsins / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009389:Neovascularization, Pathologic; D010179:Pancreas / Q000098:blood supply / Q000473:pathology / Q000601:surgery; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D011379:Prognosis; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D002403:Cathepsins