Expressions and clinical significances of c-MET, p-MET and E2f-1 in human gastric carcinoma

Abstract

BackgroundTo investigate on the expressions and the clinical significances of hepatocyte growth factor receptor (c-MET), phosphorylated c-MET (p-MET) and e2f-1 transcription factor in primary lesion of gastric adenocarcinoma (GC).MethodTissue samples from the primary lesion of GC in patients who accepted D2/D3 radical gastrectomy with R0/R1 resection were stained by immunohistochemistry of c-MET, p-MET, e2f-1 and Ki-67. The univariate and the multivariate analyses involving in clinicopathological parameters and prognostic factors were evaluated.ResultsThe positivity rates for c-MET (66.12%, 80 cases/121 cases), p-MET (59.50%, 72 cases/121 cases), e2f-1 (38.84%, 47 cases/121 cases) and Ki-67 (72.73%, 88 cases/121 cases) in primary lesion of GC was significantly higher than that in non-cancerous tissue at 5 cm places far from the margin of primary lesion (P < 0.05, respectively). The deeper tumor invasion, the severer lymph node metastasis, the later stage of TNM and the higher expression of Ki-67 was respectively an independent risk factor for the higher expression of c-MET or p-MET, but the younger age and the shorter survival time was an independent risk factor for the higher expression of e2f-1 respectively. Survival analysis showed that the worse prognosis could be observed in the patients with the combination of both c-MET-positive and e2f-1-negative (P = 0.038) or both p-MET-positive and e2f-1-negative (P = 0.042). Cox analysis demonstrated that the severer lymphatic node metastasis and the higher positivity rate of c-MET, p-MET or e2f-1 were an independent prognosis factor respectively. The higher expression of e2f-1 was identified in patients with Stage I-II, which correlated with a shorter survival time. Survival analysis also revealed that the prognosis of patients with positive expression of e2f-1 at Stage I-II was significantly worse than that in patients with negative expression of e2f-1 (χ2 = 13.437, P = 0.001). However, in the cases with Stage III-IV, no significant difference could be identified in the prognostic comparison between positive and negative expressions of e2f-1.ConclusionsThe expression of c-MET or p-MET is an independent prognosis factor. It has been observed that the higher expression of e2f-1 occurred in the early stages while the lower expression of it in the later stages in GC.

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

“…Moreover, p-MET staining is more convenient compared with MET FISH and may act as a substitute method for choosing patients for anti-MET treatment. To date, several studies have evaluated p-MET expression in gastric cancer (36)(37)(38)(39), and the results were inconsistent. The p-MET-positive rate of 6% (8/134) observed in our study is similar to the rate reported by Janjigian and colleagues, who also used the same antibody that recognizes p-MET at Y1234/1235 (37).…”

Molecular Mechanisms in Gastric Carcinogenesis

“…Wu et al analyzed 120 primary gastric cancer specimens and determined the presence of c-MET overexpression in approximately 66 % of them. Of particular significance, the authors identified a high rate of p-MET positivity (59 %) suggesting activation of MET tyrosine kinase activity [71]. In keeping with the results of previous studies, MET overexpression was found to represent an independent marker of poor prognosis [71].…”

Clinical significance of MET in gastric cancer

“…MET protein expression on immunohistochemistry (IHC) is predominantly detected in cytoplasm of tumor cells, but is also found in the cell membrane [12,[18][19][20] . Lee et al [12] assessed membranous MET expression according to a standardized technique, similar to that used to evaluate HER2 expression.…”

“…Retterspitz reported that MET was overexpressed in 51% (45 of 88) of diffuse type tumors [24] . MET overexpression has been significantly associated with tumor invasion depth [12,13,23] , lymph-node metastasis [12,13,19,20,25,26] , distant metastasis [12,13,25] , tumor stage [12,20,23,26] , and recurrence [14] , although several studies found no relation to any clinicopathological factors [24,27,28] . MET overexpression correlated with liver metastasis only in stage Ⅳ disease [29] .…”

“…Some studies showed that MET overexpression was an independent prognostic factor that was significantly related to poor survival [12][13][14]19,20,25,26,[30][31][32] . In one study, p-MET was detected in 59% (72 of 121) of GC tumors and was significantly associated with lymph-node metastasis, disease stage, and outcomes [20] . In another study, however, only 7% (2 of 30) of tumors overexpressed p-MET in spite of the fact that 63% (24 of 38) overexpressed MET [22] .…”