Neuroendocrine differentiation in colorectal carcinomas.

OBJECTIVE: To evaluate neuroendocrine differentiation in tumours from patients with colorectal carcinomas by immunostaining with antibodies against human chromogranin A (CgA) and neuron-specific enolase (NSE), and to correlate these finding with serum levels of CgA and pancreastatin-like immunoreactivity (PST-LI). We also investigated the degree of neuroendocrine differentiation found in colorectal carcinomas of different embryonic origins (hindgut and midgut). PATIENTS AND METHODS: The presence of CgA and NSE in tumours from 91 patients with colorectal carcinoma was investigated using immunohistochemistry; levels of CgA and PST-LI in sera from 55 of these patients were determined using radioimmunoassays.
RESULTS: Immunostaining for CgA and NSE was found in 15 and 36% of tumours, respectively. One or both markers of neuroendocrine differentiation were demonstrated in 40% of the colorectal carcinomas. In patients who died during the study, 23 and 51% expressed CgA and NSE in their tumours, respectively, while the corresponding values in survivors were 11 and 27% (P = 0.14 and P = 0.025, respectively). The median survival time tended to be lower in patients with neuroendocrine differentiation of their tumours than in those without such differentiation (P = 0.1). The expression of NSE was significantly higher in colorectal carcinomas derived from the midgut than in those of hindgut origin. Elevated serum levels of CgA and PST-LI were found in 38 and 43% of the patients, respectively; 62% had elevated levels of one or both markers. Of the patients with elevated serum levels of CgA or PST-LI, 44% had positive immunohistochemistry for either NSE or CgA compared with 29% of those with normal serum levels of CgA and PST-LI (P = 0.27). Serum levels of CgA were increased in a significantly higher percentage of patients with colorectal carcinomas of midgut than of hindgut origin (63 and 28%, respectively, P = 0.03). Of patients with hindgut-derived carcinomas who died during the study, 64% had raised serum values of CgA compared with 19% of those who survived (P = 0.023). The corresponding figures for PST-LI elevation were 75 and 44%, respectively (P = 0.096). In the midgut group, no difference was demonstrated for these parameters between survivors and non-survivors.
CONCLUSION: Neuroendocrine differentiation was demonstrated in 40% of the colorectal carcinomas investigated and was more frequent in midgut-derived carcinomas than in those of hindgut origin. We have shown for the first time that serum levels of CgA and PST-LI are elevated in patients with colorectal carcinomas. In accordance with previous studies, our data support the value of neuroendocrine differentiation as an indicator of poor prognosis; they also suggest a role for serum CgA and PST-LI as prognostic markers.