Heterogeneous expression of neuroendocrine marker proteins in human undifferentiated carcinoma of the colon and rectum.

The expression of neuroendocrine marker proteins 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 divided 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. Nine of twenty (45%) undifferentiated colorectal tumors expressed neuroendocrine markers (group 1). Only one patient of this group survived 2 years (11%), whereas the 2-year survival rate was 45.4% in group 0. Nine of eleven patients of group 0 were diagnosed in UICC stage I-III, whereas eight of nine tumors with expression of neuroendocrine markers were diagnosed in 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.