The level of significance CP127374 was set at P<0.05. Results Immunohistochemical analysis of c-Met in human CC specimens c-Met staining was localised in both the cell membrane and cytoplasm of CC cells (Figure 1). Strong immunostaining for c-Met was apparent at the luminal cell surface of neoplastic glands and ducts of adenocarcinoma. Positive staining for c-Met was demonstrated in 143 (57.9%, 95% CI: 51.7�C64.1) of the 247 cases of CC overall, 50 (45.0%, 95% CI: 35.7�C54.3) of the 111 cases of IHCC, and 93 (68.4%, 95% CI: 60.6�C76.2) of the 136 cases of EHCC; high c-Met expression (2+) was demonstrated in 35 (14.2%, 95% CI: 9.8�C18.6) of the 247 cases of CC overall, 13 (11.7%, 95% CI: 5.7�C17.7) of the 111 cases of IHCC, and 22 (16.2%, 95% CI: 10.0�C22.4) of the 136 cases of EHCC.

When compared with EGFR staining, we occasionally observed coexpression of c-Met and EGFR (Figure 2). Figure 1 c-Met expression in primary CC cases. (A) c-MET expression was exclusively detected in tumour cells (T), but not in non-cancerous bile duct epithelium (N). (B�CD) Representative IHC pictures of higher magnification of c-Met expression (expression … Figure 2 A representative case showing coexpression of c-Met (A) and EGFR (B) in adjacent sections of the same tumour. Scale bar indicates 200��m. c-Met and EGFR expression in CC cell lines Expression of c-Met, phospho-Met, EGFR, and phospho-EGFR in ten CC cells and one gastric cancer cells were estimated by Western blotting (Figure 3). Expression of c-Met was observed in nine CC cells. Coexpression of c-Met and EGFR was detected in eight of them (except NCC-CC3-1).

Prominent c-Met phosphorylation was detected in five cell lines (HuCCT1, OZ, NCC-BD2, TGBC24TKB, and NCC-BD1) and simultaneous activation of c-Met and EGFR was observed in seven cell lines including these five. Figure 3 Immunoblot analysis of c-Met, phosphorylated-Met pY1234/1235), EGFR, and phosphorylated EGFR (pY1173) in CC cell lines. MKN45 cell (a human gastric cancer cell) is a positive control of c-Met and phosphorylated-Met expression (Smolen et al, 2006). �� … Correlations between c-Met and clinicopathological factors The relationships between c-Met expression and clinicopathological factors of IHCC and EHCC were evaluated and are shown in Tables 1 and and2.2. Increased expression of c-Met was significantly correlated with overexpression of EGFR in IHCC (P=0.

0063), and histopathological classification (P=0.0239) and overexpression of EGFR (P=0.0056) in EHCC. No other clinical factors were associated with c-Met expression. Table 1 Comparison of clinicopathological factors between patients with high and low c-Met expression in IHCC Table Cilengitide 2 Comparison of clinicopathological factors between patients with high and low c-Met expression in EHCC Five-year survival for patients in the c-Methigh and c-Metlow groups was 15.4 and 41.1% (P=0.0013) for IHCC and 40.9 and 45.8% (P=0.