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).


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.


CONCLUSIONS
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.
Syversen
U
U
Institute of Cancer Research, University of Trondheim, Norway.
Halvorsen
T
T
Mårvik
R
R
Waldum
H L
HL
D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis*; D003106:Colon / Q000737:chemistry / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000097:blood / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009490:Neurosecretory Systems / Q000473:pathology*; D010187:Pancreatic Hormones / Q000032:analysis*; D010751:Phosphopyruvate Hydratase / Q000032:analysis*; D011863:Radioimmunoassay; D015996:Survival Rate
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D002864:Chromogranins; D010187:Pancreatic Hormones; C071102:pancreastatin-52; D010751:Phosphopyruvate Hydratase