The use of molecular profiling of early colorectal cancer to predict micrometastases.
BACKGROUND
Approximately one third of node-negative colorectal cancers (CRCs) recur, suggesting the failure to detect occult disease. Lymphatic mapping followed by focused analysis of the sentinel node is highly accurate in identifying micrometastases.


OBJECTIVE
Because aberrant genetic changes occur early in tumor progression and are associated with lymphatic metastases, we hypothesized that the molecular profiling of specific tumor markers in the primary tumor might predict that tumor's metastatic potential.


METHODS
A prospective patient series.


METHODS
Forty consecutive patients with early CRC underwent lymphatic mapping after subserosal injection of 1 mL of isosulfan blue dye. All lymph nodes were examined by hematoxylin-eosin (HE) staining, and multiple sections of each sentinel node were examined by HE and cytokeratin immunohistochemistry (CK-IHC) staining. Primary tumors were analyzed for p53 expression using IHC staining and for beta-human chorionic gonadotropin (beta-hCG), hepatocyte growth factor receptor (c-Met), and universal melanoma antigen (uMAGE) messenger RNA expression using reverse-transcriptase polymerase chain reaction and electrochemiluminescence.


RESULTS
Nine patients (23%) had positive nodes by routine HE staining. Of the remaining 31 patients with negative nodes on HE staining, 8 tumors (26%) were upstaged by CK-IHC identification of occult micrometastases. There was a direct correlation between the number of markers and the T stage (P =.001). The expression of p53, beta-hCG, c-Met, and uMAGE in primary tumors was significantly higher in the presence of nodal micrometastases vs no metastases (P =.03).


CONCLUSIONS
Sentinel lymphatic mapping is an accurate method of detecting micrometastases in CRC. Molecular profiling of primary CRC tumors, similar to that used for breast cancer, may be important in predicting metastatic potential and determining which patients may benefit from adjuvant therapy.
Bilchik
Anton J
AJ
Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404, USA. bilchika@jwci.org
Nora
Dean T
DT
Saha
Sukamal
S
Turner
Roderick
R
Wiese
David
D
Kuo
Christine
C
Ye
Xing
X
Morton
Donald L
DL
Hoon
Dave S B
DS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012394:Rosaniline Dyes; D021701:Sentinel Lymph Node Biopsy; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018997:Chorionic Gonadotropin, beta Subunit, Human; D012394:Rosaniline Dyes; D016159:Tumor Suppressor Protein p53; C025484:iso-sulfan blue; D019859:Proto-Oncogene Proteins c-met