title: Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG).
abstract: Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information.
authors.affiliation: Department of Surgery, Leiden University Hospital, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Songun
authors.forename: C J
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: J
authors.initials: J
authors.lastname: Hermans
authors.forename: S T
authors.initials: ST
authors.lastname: Pals
authors.forename: H W
authors.initials: HW
authors.lastname: Verspaget
authors.forename: A N
authors.initials: AN
authors.lastname: Vis
authors.forename: A G
authors.initials: AG
authors.lastname: Menon
authors.forename: S V
authors.initials: SV
authors.lastname: Litvinov
authors.forename: J H
authors.initials: JH
authors.lastname: van Krieken
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009504:Neutrophils; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012044:Regression Analysis; D016160:Retinoblastoma Protein / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein