Overexpression of c-erbB-2 oncoprotein has been shown to correlate with poor prognosis and drug-resistance to the conventional chemotherapy with 5-fluorouracil in breast and gastric cancers. To evaluate the clinical significance of c-erbB-2
overexpression in colorectal cancer, immunohistochemical staining was performed with the paraffin-embedded tissues of 141 colorectal cancer patients with curative surgery.
The follow-up duration ranged from 7 to 61 months(median 30 months). Two-year disease-free and overall survival rate of the total patients were 77%, 91%, respectively. The c-erbB-2 positive rate was 24.8%. Even if patients with c-erbB-2
overexpression
showed a tendency of poor prognosis than c-eerbB-2 negative patients, T-factor and the TNM stage were independent prognostic factors in multivariate analysis. In subset analysis with c-erbB-2 negative patients, there were no differences in
recurrence
rate and 2-year disease-free survival rate between patients with chemotherapy and without chemotherapy(20.0% versus 26.1%)(80.0% versus 82.0%). However, in c-erbB0-2 positive patients, those subgroup with chemotherapy showed tendencies toward
advantages
in relapse rate and 2-year disease-free survival rate than those of subgroup without chemotherapy(21.0% versus 50.0%; p=0.09)(76.0% versus 50.0%; p=0.06). Also, there was a tendency of increased time to relapse in patients with chemotherapy
comparing to
that of the patient without chemotherapy(7.5 months versus 17.0 months; p=0.09). In stage Ⅲ, patients with c-erbB-2 overexpression showed increased 2-year disease-free survival rate with chemotherapy as comparing to that of patients without
chemotherapy(81.0% versus 29.0%;=0.003). Again, this survival benefit was not found in c-erbB-2 negative stage Ⅲ patients regardless of chemotherapy.
In conclusion, c-erbB-2 overexpression might be a marker of relative drug resistance to 5-FU which will be converted with the high dose treatment of modulation with leucovorin. A prospective randomized trial is warrented to confirm this
suggestion
and
for the clinical application of c-erbB-2 overexpression.
|