Guanylyl cyclase C messenger RNA is a biomarker for recurrent stage II colorectal cancer.
BACKGROUND
Patients with stage II colorectal cancer and no histologic evidence of lymph node invasion develop recurrent disease, presumably because of undetected micrometastases. Guanylyl cyclase C is expressed by intestinal and colorectal cancer cells but not by extraintestinal tissues or tumors.


OBJECTIVE
To examine the expression of guanylyl cyclase C messenger RNA (mRNA) in lymph nodes of patients with node-negative colorectal cancer who did and did not have recurrent disease.


METHODS
Case-control study.


METHODS
Tertiary care academic medical center.


METHODS
Paraffin-embedded lymph nodes were obtained from 21 patients with histologically confirmed node-negative colorectal cancer who had undergone resection. Controls included 11 patients without disease recurrence 6 or more years after resection, and case-patients included 10 patients whose disease recurred up to 3 years after resection.


METHODS
Sections of paraffin-embedded lymph nodes were obtained from each patient and were pooled, and their RNA was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR).


RESULTS
Guanylyl cyclase C mRNA was expressed in lymph nodes from all patients with recurrent disease but not in those from patients without recurrent disease (P = 0.004). Nested RT-PCR that used primers for carcinoembryonic antigen, a marker for colorectal cancer, identified carcinoembryonic antigen mRNA in lymph nodes from only 1 of 10 patients with recurrent disease and those from 0 of 11 patients without recurrent disease. The odds ratio for death associated with expression of guanylyl cyclase C mRNA in regional lymph nodes was 15.0 (95% CI, 1.1 to 756.7).


CONCLUSIONS
Expression of guanylyl cyclase C mRNA in lymph nodes is associated with recurrence of colorectal cancer in patients with stage II disease. Analysis of guanylyl cyclase mRNA expression by RT-PCR may be useful for colorectal cancer staging.
Cagir
B
B
Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Gelmann
A
A
Park
J
J
Fava
T
T
Tankelevitch
A
A
Bittner
E W
EW
Weaver
E J
EJ
Palazzo
J P
JP
Weinberg
D
D
Fry
R D
RD
Waldman
S A
SA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002272:Carcinoembryonic Antigen / Q000032:analysis; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006162:Guanylate Cyclase / Q000032:analysis* / Q000235:genetics; D006801:Humans; D008198:Lymph Nodes / Q000201:enzymology*; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000473:pathology; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis*; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D018000:Receptors, Peptide; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled