C-erbB-2 oncoprotein content in colorectal cancer and in surrounding mucosa: relationship with clinicopathologic parameters and prognostic significance.

BACKGROUND

c-erbB-2 is a transmembrane signaling molecule closely related in structure to the epidermal-growth-factor receptor (EGFR) but biologically distinct from it. c-erbB-2 has been implicated in cell transformation and tumor pathogenesis, but very little is known about its content and clinical significance in colorectal cancer.

AIMS

To evaluate the c-erbB-2 content in colorectal cancer and its possible relationship with clinicopathologic parameters from tumors and prognostic significance.

METHODS

Membranous and cytologic c-erbB-2 oncoprotein contents were examined by an immunoenzymatic assay in tumors and paired normal surrounding mucosa samples from 131 colorectal cancer patients. In addition, survival analysis were prospectively performed in a subgroup of 69 consecutive patients with resectable colorectal carcinomas, who underwent a mean follow-up period of 28 months.

RESULTS

In the overall group of patients, c-erbB-2 levels were significantly higher in membranous than in cytosolic samples, in neoplastic tissues (5,830.4 +/- 1085.3 vs. 934.2 +/- 107.5 NHU/mg protein; p < 0.0001) and in surrounding normal mucosa samples (5,257.8 +/- 646.3 vs. 837.4 +/- 187.4 NHU/mg protein; p < 0.0001). Nevertheless, a significant positive relation was found between membranous and cytosolic oncoprotein levels in these two paired sets (p < 0.0001, for both). There were no significant differences in membranous or cytosolic c-erbB-2 protein levels between neoplastic tissues and surrounding mucosa samples in this overall group of patients. In addition, the results did not show significant correlations of these oncoprotein contents with clinicopathologic parameters from tumors such as location, stage, histologic grade, and DNA content or S-phase fraction. However, the results indicated that low membranous c-erbB-2 content (< 4,500 NHU/mg protein) in tumors predict shorter relapse-free survival and overall survival (p < 0.05, for both) in resectable colorectal cancer patients.

CONCLUSIONS

There are a wide variability of both membranous and cytologic c-erbB-2 contents in colorectal carcinomas, which seems to correspond to the biological heterogeneity of these tumors. In addition, our results also demonstrate that high membranous c-erbB-2 levels are associated with lesions of favorable evolution in resectable colorectal cancer patients.