The expression of matrix metalloproteinases-2 and -9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters.
OBJECTIVE
To investigate the expression of metalloproteinase (MMP) -2, MMP-9 and tissue inhibitor of MMP (TIMP) -2 in pancreatic ductal and ampullary carcinoma and to test the findings for correlation with angiogenesis and several clinicopathological parameters.


METHODS
Paraffin sections from 32 pancreatic ductal adenocarcinomas and 17 ampullary carcinomas were assessed for the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemistry. Stromal and epithelial staining was evaluated separately. Moreover, sections stained immunohistochemically with anti-CD34 antibody were evaluated by image analysis for the quantification of microvessel density (MVD).


RESULTS
In pancreatic ductal adenocarcinoma, lower levels of glandular TIMP-2 were found in poorly differentiated tumors, while high glandular TIMP-2 expression was significantly associated with better survival. The age of the patients and the degree of differentiation of the tumor were identified as independent prognostic parameters. No relation was found between the expression of MMPs, TIMP or angiogenesis and the parameters under consideration. In ampullary adenocarcinoma, strong expression of glandular MMP-2 was associated with higher MVD values. Moreover, lymph vessel invasion was associated with higher stromal TIMP-2.


CONCLUSIONS
In pancreatic ductal adenocarcinoma, TIMP-2 may have a more crucial role in prognosis than MMP-2, MMP-9 or angiogenesis. In ampullary adenocarcinoma, MMP-2 expression correlated with MVD, supporting its postulated role in angiogenesis.
Giannopoulos
George
G
4th Surgical Department, Attikon Hospital, University of Athens, Athens, Greece. geogianno@med.uoa.gr
Pavlakis
Kitty
K
Parasi
Aikaterini
A
Kavatzas
Nikolaos
N
Tiniakos
Dina
D
Karakosta
Antigoni
A
Tzanakis
Nikolaos
N
Peros
George
G
D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis*
D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9