Preoperative serum levels of the carcinoembryonic antigen in hereditary non-polyposis colorectal cancer compared to levels in sporadic colorectal cancer.
BACKGROUND
Carcinoembryonic antigen (CEA) serves as the most widely used and most cost-effective tumor marker in colorectal cancer for almost 30 years. Recent publications about serum CEA levels are based on patient groups without definite differentiation between hereditary and non-hereditary forms of colorectal cancer.


METHODS
We compared preoperative CEA serum levels from 105 patients with hereditary non-polyposis colorectal cancer (HNPCC) and 107 patients with sporadic colorectal cancer including influences of age and Dukes stage. CEA values in cases of HNPCC were correlated to the findings of microsatellite analyses, mutation analyses of the MMR genes (MLH1, MSH2) and respective immunohistochemistries.


RESULTS
Thirty-three HNPCC patients (31%) and 37 patients with sporadic CRC (34%) revealed elevated CEA levels higher than 5 ng/ml. The mean preoperative CEA level in all Dukes stages of HNPCC patients was lower with 31.7 +/- 180 ng/ml than in sporadic colorectal cancer with 68.3 +/- 424 ng/ml, but without significance (p = 0.72). HNPCC tumors with signs of de-differentiation (G3 and G4) revealed significantly higher CEA values with 62.2 +/- 262 ng/ml in comparison to well-differentiated tumors (G1 and G2) with 5.0 +/- 9.6 ng/ml (p = 0.02). HNPCC patients with "classical characteristics" (high microsatellite instability (MSI), MMR gene mutation, loss of MMR protein expression) had lower preoperative CEA serum levels than those without equivalent genetic alterations, but without reaching statistical significance. CEA levels of HNPCC tumors increased significantly under occurrence of metastases with mean values of 170.3 +/- 343 (p < 0.02).


CONCLUSIONS
Normal preoperative serum CEA levels do not have the same validity for all colorectal cancer patients. Low CEA levels in HNPCC patients could occur due to well-differentiated tumors and should be considered more critically than in sporadic CRC patients. Further studies including comparison of postoperative CEA development are necessary to elucidate the importance of these results.
Schiemann
Uwe
U
Medizinische Klinik, München, Germany. uwe.schiemann@insel.ch
Günther
Silke
S
Gross
Manfred
M
Henke
Gaby
G
Müller-Koch
Yvonne
Y
König
August
A
Muders
Michael
M
Folwaczny
Christian
C
Mussack
Thomas
T
Holinski-Feder
Elke
E
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D002352:Carrier Proteins / Q000235:genetics; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011300:Preoperative Care; D012680:Sensitivity and Specificity
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein