H pylori status and angiogenesis factors in human gastric carcinoma.
OBJECTIVE
To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels.


METHODS
Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively.


RESULTS
A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026).


CONCLUSIONS
H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.
Mangia
Anita
A
Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola 209, Bari 70126, Italy.
Chiriatti
Annalisa
A
Ranieri
Girolamo
G
Abbate
Ines
I
Coviello
Maria
M
Simone
Giovanni
G
Zito
Francesco Alfredo
FA
Montemurro
Severino
S
Rucci
Antonello
A
Di Leo
Alfredo
A
Tommasi
Stefania
S
Berloco
Pasquale
P
Xu
Jian Ming
JM
Paradiso
Angelo
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D016159:Tumor Suppressor Protein p53; C074689:VacA protein, Helicobacter pylori; D042461:Vascular Endothelial Growth Factor A; C080866:cagA protein, Helicobacter pylori; D013939:Thymidine Phosphorylase; D040262:Receptors, Vascular Endothelial Growth Factor