Microarray versus conventional prediction of lymph node metastasis in colorectal carcinoma.
BACKGROUND
The authors investigated whether microarray-based gene expression analysis of primary tumor biopsy material could be used to predict lymph node status in patients with colorectal carcinoma (CRC). Lymphatic metastasis strongly determines treatment algorithms in CRC. Currently, postoperative histology results are needed to determine lymph node status. Reliable preoperative information would be useful to advance treatment strategies.


METHODS
In specimens from 66 patients with CRC from the Erlangen Registry of Colorectal Cancer, 41 shock-frozen samples of International Union Against Cancer (UICC) Stage I-II CRC and 25 samples of UICC Stage III CRC were microdissected manually, RNA was isolated, and gene chips (HG-U133A; Affymetrix) were hybridized. Prediction rates for lymphatic metastasis were calculated using conventional clinicopathologic parameters, gene expression data, and a combination of both. Prediction error, specificity, and sensitivity were analyzed using six different statistical classifiers.


RESULTS
Analysis of conventional parameters produced a positive prediction rate that ranged between 53% and 61%, sensitivity of 42%, and specificity of 72%. Microarray prediction rates were between 62% and 67% for lymphatic metastasis. Specificity was between 76% and 83%, and sensitivity was between 38% and 48%, depending on the statistical procedure. The conventional estimates were improved by 9-12% when array data were added.


CONCLUSIONS
Current data show that the prediction of lymphatic metastasis can be improved by gene expression profiling of the primary tumor biopsy, alone or in combination with conventional parameters. Gene expression profiling may become valuable increasingly in planning treatment for patients with CRC.
Croner
Roland S
RS
Department of Surgery, University of Erlangen, Erlangen, Germany. roland.croner@chir.imed.uni-erlangen.de
Peters
Andrea
A
Brueckl
Wolfgang M
WM
Matzel
Klaus E
KE
Klein-Hitpass
Ludger
L
Brabletz
Thomas
T
Papadopoulos
Thomas
T
Hohenberger
Werner
W
Reingruber
Bertram
B
Lausen
Berthold
B
D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D012680:Sensitivity and Specificity