Expression of neuroendocrine markers: a signature of human undifferentiated carcinoma of the colon and rectum.

The frequency and prognostic significance of neuroendocrine marker expression in undifferentiated colorectal cancers has not yet been studied in great detail. Therefore, the survival of 20 patients with small cell undifferentiated colorectal cancers, treated at our institution between 1982 and 1997 (0.8% of all operated colorectal carcinomas), was correlated with the extent of neuroendocrine differentiation. Chromogranin A, synaptophysin, syntaxin1, VAMP2, SNAP25 and alpha/beta-SNAP were used as neuroendocrine markers. Based on the degree of immunoreactivity for these marker proteins, tumors were separated into group 0 (<2% cells stained positive for neuroendocrine markers) and group 1 (>2% cells stained positive). Patients were followed up for at least 5 years or until death. Of 20 (45%) undifferentiated colorectal tumors, 9 expressed neuroendocrine markers (group 1). Only one patient of this group survived for 2 years (11%), whereas the 2-year-survival rate was 45.4% in group 0. Of the 11 patients in group 0, 9 were diagnosed with UICC stages I-III, whereas 8 of 9 tumors with expression of neuroendocrine markers were diagnosed with UICC stage IV ( P=0.002). Our results show that neuroendocrine differentiation is often seen in small cell undifferentiated colorectal cancer. It correlates with a more aggressive course of the disease.