OBJECTIVETo investigate the expression of transcription factor Sp1 in gastric cancer tissue and its correlation with prognosis.

METHODSSp1 expression patterns in specimens of 86 gastric cancers, 57 normal gastric tissues and 53 metastatic lymph nodes were detected by immunohistochemical method. The activity of Sp1 in the tumor and normal tissues was examined by electrophoretic mobility shift analysis (EMSA). The correlation between transcription factor Sp1 expression of tumors and patients' prognosis were statistically analyzed using Cox proportional hazard model.

RESULTSIn normal gastric tissue, Sp1 protein was predominantly expressed in the nuclei of cell located in the mucous neck region, but neither in the gastric pit cells with foveolar differentiation, nor in cells of the glandular epithelium with glandular differentiation. Strong Sp1 expression was also detected in tumor cells, but very weak or even no Sp1 expression in stromal cells or normal glandular cells surrounding the tumor. The median survival time of patients with negative, weak, and strong Sp1 expression was 43, 37, and 8 months, respectively (P < 0.01). Spl expression (P < 0.01) and stage (P < 0.001) were demonstrated as independent prognostic factor by multivariate analysis.

CONCLUSIONNormal and malignant gastric tissue are found to have its own unique Sp1 expression patterns. Sp1 expression may be used as an important survival predictor in human gastric cancer.

Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Papillary ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Blotting, Western ; statistics & numerical data ; Cell Nucleus ; metabolism ; Electrophoretic Mobility Shift Assay ; Female ; Follow-Up Studies ; Gastric Mucosa ; chemistry ; pathology ; Humans ; Immunohistochemistry ; statistics & numerical data ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Sp1 Transcription Factor ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Survival Analysis

Purpose: Nodal downstaging after preoperative therapy for gastric cancer has been shown to impart excellent prognosis, but this has not been validated in a national cohort. The role of neoadjuvant chemoradiation (NACR) in nodal downstaging remains unclear when compared with that of neoadjuvant chemotherapy alone (NAC). Furthermore, it is unknown whether the prognostic implications of nodal downstaging differ by preoperative regimen. Materials and Methods: Using the National Cancer Database, overall survival (OS) duration was compared among natural N0 (cN0/ypN0), downstaged N0 (cN+/ypN0), and nodepositive (ypN+) gastric cancer patients treated with NACR or NAC. Factors associated with nodal downstaging were examined in a propensity score-matched cohort of cN+ patients, matched 1:1 by receipt of NACR or NAC. Results: Of 7,426 patients (natural N0 [n=1,858, 25.4%], downstaged N0 [n=1,813, 24.4%], node-positive [n=3,755, 50.4%]), 58.2% received NACR, and 41.9% received NAC. The median OS durations of downstaged N0 (5.1 years) and natural N0 (5.6 years) patients were similar to one another and longer than that of node-positive patients (2.1 years) (P<0.001). In the matched cohort of cN+ patients, more recent diagnosis (2010–2015 vs. 2004–2009) (odds ratio [OR], 2.57; P<0.001) and NACR (OR, 2.02; P<0.001) were independently associated with nodal downstaging. The 5-year OS rate of downstaged N0 patients was significantly lower after NACR (46.4%) than after NAC (57.7%) (P=0.003). Conclusions Downstaged N0 patients have the same prognosis as natural N0 patients.Nodal downstaging occurred more frequently after NACR; however, the survival benefit of nodal downstaging after NACR may be less than that when such is achieved by NAC.