p27KIP1 expression in gastric cancer: differential pathways in the histological subtypes associated with Helicobacter pylori infection.
OBJECTIVE
Decreases in p27(KIP1) and C-MYC expression have been associated with Helicobacter pylori infection. Furthermore, C-MYC seems to be a transcriptional repressor of p27(KIP1). Therefore, in a series of gastric adenocarcinomas we studied the association of p27(KIP1) expression with H. pylori genotype (vacA, cagA, cagE and virB11) and the involvement of C-MYC in this process.


METHODS
Expression of p27(KIP1) and C-MYC was determined by immunohistochemistry in 84 gastric adenocarcinoma samples and H. pylori infection and genotype were determined by polymerase chain reaction.


RESULTS
Most p27(KIP1)-negative cases (94.0%) were H. pylori-positive and 44.8% were C-MYC-positive. In the diffuse gastric cancer subtype, p27-negative-C-MYC-positive was the most frequent combination (cluster II), and was associated with the more pathogenic H. pylori strains. Although an association with p27(KIP1) and H. pylori strain was found in the intestinal gastric cancer subtype, negativity for p27(KIP1) and C-MYC markers was the most frequent cluster, followed by cluster II, and both were present, independent of the H. pylori genotype.


CONCLUSIONS
Reduced expression of p27(KIP1) was closely linked to H. pylori infection, and was dependent on the more pathogenic strains. Moreover, intestinal and diffuse subtypes showed distinct carcinogenic pathways influenced by H. pylori strains. These data add insight to the differential influence and relevance of H. pylori genotype in gastric cancer development.
Alves
Markênia Kélia Santos
MK
Department of Pathology and Forensic Medicine, Section of Microbiology, Federal University in Ceará, Fortaleza, Brazil. markenialves@yahoo.com.br
Lima
Valeska Portela
VP
André
Angela Rosa
AR
Ferreira
Márcia Valéria Pitombeira
MV
Barros
Marcos Aurélio Pessoa
MA
Rabenhorst
Silvia Helena Barem
SH
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D016009:Chi-Square Distribution; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004587:Electrophoresis, Agar Gel; D005260:Female; D005743:Gastrectomy; D005838:Genotype; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000601:surgery
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; C103937:PicB protein, Helicobacter pylori; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D050760:Cyclin-Dependent Kinase Inhibitor p27