Metastasis-associated protein S100A4 and p53 predict relapse in curatively resected stage III and IV (M0) gastric cancer.
OBJECTIVE
Pathologic stage is the most important predictive factor of relapse in gastric cancer after curative resection. However, patients with the same stage often have different risks of relapse. Here, we investigated whether the expressions of molecular markers can supplement the current staging system in terms of relapse prediction.


METHODS
One hundred and nine stage III or IV (M0) patients who had received curative gastrectomy followed by adjuvant 5-fluorouracil and cisplatin chemotherapy were included in this study. The expressions of molecular markers including p53, p27, COX-2, HER-2, EGFR, maspin, S100A4, E-cadherin, Sp1, and p97 were analyzed by immunohistochemistry in cancer and paired normal tissues.


RESULTS
The overall relapse rate was 58.7%, and pathologic stage was a significant predictive factor of relapse (42% in stage IIIA, 48% in IIIB, 76% in IV, p = 0.005). Of the 10 markers examined, p53 and S100A4 were expressed only in tumor tissues, and S100A4 expression was significantly associated with a higher relapse rate (85% vs. 53%, p = 0.008). In multivariate analysis including tumor stage, S100A4 and p53 expression were independent predictive factors of relapse (relative risk, 6.98; 95% confidence interval [CI], 1.608-30.342, 3.49; 95% CI, 1.328-9.186, respectively). On comparing patients who expressed S100A4 or p53 with those who expressed neither, relapse rates were 58% vs. 25% in stage III (p = 0.011) and 95% vs. 59% in stage IV (M0) (p = 0.003).


CONCLUSIONS
In addition to staging system, the expressions of S100A4 and p53 were significant predictive factors of relapse in gastric cancer after curative resection and adjuvant chemotherapy.
Kim
Yu Jung
YJ
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kim
Min A
MA
Im
Seock-Ah
SA
Kim
Tae Min
TM
Kim
Dong-Wan
DW
Yang
Han-Kwang
HK
Heo
Dae Seog
DS
Lee
Kuhn-Uk
KU
Choe
Kuk Jin
KJ
Kim
Noe Kyeong
NK
Kim
Tae-You
TY
Kim
Woo Ho
WH
Bang
Yung-Jue
YJ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D048053:Mitogen-Activated Protein Kinase 6 / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D015820:Cadherins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D048053:Mitogen-Activated Protein Kinase 6; D018719:Erb-b2 Receptor Tyrosine Kinases; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D015843:Serpins; D016329:Sp1 Transcription Factor; D016159:Tumor Suppressor Protein p53; C085344:SERPIN-B5; C495901:TP53 protein, human; C077591:S100A4 protein, human; C496540:PTGS2 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human