Predictive and prognostic role of E-cadherin protein expression in patients with advanced gastric carcinomas treated with palliative chemotherapy.
Loss of E-cadherin expression has been related with an adverse outcome in patients with resected gastric cancer. More recently, experimental models with cancer cell lines showed that chemosensitivity may be affected by the E-cadherin expression status. We investigated whether E-cadherin expression is correlated with the response to chemotherapy and the survival of patients with advanced gastric cancer. Consecutive patients with advanced gastric cancer who underwent palliative chemotherapy were considered eligible for study entry. Measurable disease, complete follow-up information and availability of tumor specimens for immunohistochemistry were mandatory inclusion criteria. In 70 assessable patients, 30 patients had locoregional disease and 40 patients had visceral metastases. Chemotherapy consisted of cisplatin/fluorouracil/folinic acid in 33 patients and cisplatin/fluorouracil/epirubicin/folinic acid in 37 patients. There were 13 patients with complete response, 20 with partial response, 20 with stable disease and 17 patients progressed. Thirty-eight patients had > 80% E-cadherin-positive cancer cells (positive E-cadherin expression); 15 cases showed 25-70% (reduced E-cadherin expression), and in the remaining 17 cases E-cadherin expression was < 10% (negative E-cadherin expression). The response to chemotherapy was unrelated to the E-cadherin expression status. Conversely, survival in the 32 patients with reduced/negative E-cadherin expression (25 weeks) was significantly worse than that observed in the 38 patients with preserved E-cadherin expression (36 weeks) (p < 0.01). E-cadherin expression retained its independent prognostic role in the multivariate analysis. E-cadherin expression may give prognostic information in patients with advanced gastric cancer, but it does not seem to possess a predictive role in vivo. Some of the mechanisms inducing E-cadherin downregulation, like hypermethylation, may be potentially reversible, and they deserve further investigation as the target of novel therapeutic strategies.
Graziano
Francesco
F
Medical Oncology Unit, Hospital of Urbino, Urbino, Italy. frada@tin.it
Mandolesi
Alessandra
A
Ruzzo
Annamaria
A
Bearzi
Italo
I
Testa
Enrica
E
Arduini
Federica
F
Silva
Rosarita
R
Muretto
Pietro
P
Mari
Davide
D
Berardi
Rossana
R
Scartozzi
Mario
M
Lai
Vittorio
V
Cascinu
Stefano
S
Magnani
Mauro
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis*; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010166:Palliative Care; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D015820:Cadherins; D015251:Epirubicin; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil