KLF4 expression and apoptosis-related markers in gastric cancer.
OBJECTIVE
To correlate the expression of Kruppel-like factor 4 (KLF4) with clinicopathological properties of gastric cancer (GC) and to evaluate any possible correlation between KLF4 expression and the expression of apoptosis-related markers p53, Fas, Bcl-2, survivin and FLICE inhibitory protein (Flip-l).


METHODS
Formalin-fixed, paraffin-embedded tissue specimens obtained from 96 patients with GC who had undergone gastric surgery were analyzed for pathological parameters, while KLF4, p53, Fas, Bcl-2, survivin and Flip-l expression was assessed by immunohistochemistry.


RESULTS
TKLF4 immunohistochemical staining was noted in 78.1% of the cases. Strong positivity was found in 15.6% and weak in 62.5% of the samples. Positive expression of p53, Fas, Bcl-2, survivin, Flip-l was found in 56.2%, 44.8%, 15.6%, 41.7% and 38.5% of the samples, respectively. KLF4 expression was significantly associated with p53 nuclear staining and Fas immunoreactivity. p53-positive tumors demonstrated more often high KLF4 staining compared to p53-negative tumors. Fas-positive tumors were associated with decreased KLF4 expression. Logistic regression analysis of apoptosis-related markers to KLF4 expression revealed that Fas positivity significantly decreased the probability of strong KLF4 expression, and inversely, Bcl-2 expression improved the prediction of KLF4 staining. When all 5 predictive variables were considered together (p53, Fas, survivin, Bcl-2, Flip-l) they significantly predicted the type of KLF4 expression in GC cells (p=0.019).


CONCLUSIONS
Our results suggest that the decrease or loss of KLF4 expression correlates with diffuse-type GC and immunoreactivity to Fas, and are inversely linked with p53 nuclear accumulation. The significance of KLF4 in GC requires further studies and should be more thoroughly investigated for potential use in the evaluation and better stratification of GC patients.
Institute of Pathology, Faculty of Medicine, University of Nis, Nis, Serbia.
M
M
Krstic
S
S
Stojnev
L
L
Jovanovic
G
G
Marjanovic
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C491901:FAS protein, human; D051034:Inhibitor of Apoptosis Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; C434062:TNIP2 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor