Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer

Abstract

Preoperative staging of gastric cancer is difficult and not optimal. The TNM stage is an important prognostic factor, but it can only be assessed reliably after surgery. Therefore, there is need for additional, reliable prognostic factors that can be determined preoperatively in order to select patients who might benefit from (neo) adjuvant treatment. Expression of immunohistochemical markers was demonstrated to be associated with tumour progression and metastasis. The expression of p53, CD44 (splice variants v5, v6 and v9), E-cadherin, Ep-CAM (CO17-1A antigen) and c-erB2/neu were investigated in tumour tissues of 300 patients from the Dutch Gastric Cancer Trial, investigating the value of extended lymphadenectomy compared to that of limited lymphadenectomy). The expression of tumour markers was analysed with respect to patient survival. Patients without loss of Ep-CAM-expression of tumour cells (19%) had a significantly better 10-year survival (Po0.0001) compared to patients with any loss: 42% (s.e. ¼ 7%) vs 22% (s.e. ¼ 3%). Patients with CD44v6 (VFF18) expression in more than 25% of the tumour cells (69% of the patients) also had a significantly better survival (P ¼ 0.01) compared to patients with expression in less than 25% of the tumour cells: 10 year survival rate of 29% (s.e. ¼ 3%) vs 19% (s.e. ¼ 4%). The prognostic value of both markers was stronger in stages I and II, and independent of the TNM stage. Ep-CAM and CD44v6-expression provides prognostic information additional to the TNM stage. Loss of Ep-CAMexpression identifies aggressive tumours especially in patients with stage I and II disease. This information may be helpful in selecting patients suitable for surgery or for additional treatment pre-or postoperatively.

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

“…A similar correlation was reported for gastric cancers (Songun et al, 2005). Very little information is currently available with regard to the correlation of Ep-CAM expression with survival and tumour staging for colon and lung cancers, while more recent studies have explored larger sample numbers of gastric (Songun et al, 2005) and prostate cancers (Poczatek et al, 1999;Zellweger et al, 2005) for Ep-CAM expression.…”

“…Epithelial cell adhesion molecule upregulation was an independent marker for poor survival in lymph node positive breast cancers , and gall bladder cancers (Varga et al, 2004). In contrast, improved survival was found associated with Ep-CAM upregulation in clear cell renal cell carcinoma (Kim et al, 2004;Seligson et al, 2004;Went et al, 2005), and gastric cancers (Songun et al, 2005). Here, we observed that survival of patients in the subgroup of moderately differentiated colon cancers also showed a significant positive correlation with Ep-CAM expression.…”

“…In clear cell renal cell carcinoma, Ep-CAM expression is infrequent, but patients with Ep-CAM overexpressing tumours show a trend to better survival (Kim et al, 2004;Seligson et al, 2004;Went et al, 2005). A similar correlation was reported for gastric cancers (Songun et al, 2005). Very little information is currently available with regard to the correlation of Ep-CAM expression with survival and tumour staging for colon and lung cancers, while more recent studies have explored larger sample numbers of gastric (Songun et al, 2005) and prostate cancers (Poczatek et al, 1999;Zellweger et al, 2005) for Ep-CAM expression.…”

EpCAM an immunotherapeutic target for gastrointestinal malignancy: current experience and future challenges

“…Patients without loss of EpCAM expression of tumour cells (19%) had a significantly better 10-year survival compared with patients with any loss: 42 vs 22%. The prognostic value was stronger in stages I and II, and independent of the TNM stage (Songun et al, 2005).…”

Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity

“…There are some clinical reports about the relation of Ep-CAM expression to the prognosis, but the significance is uncertain; high-Ep-CAM expression was described as a good prognostic factor (Seligson et al, 2004;Songun et al, 2005;Kimura et al, 2007), while in some reports highEp-CAM expression led to poor prognosis (Gastl et al, 2000;Varga et al, 2004;Stoecklein et al, 2006). Following this discrepancy, Ep-CAM may have a different role in each type of cancer.…”