Evaluation of guanylyl cyclase C lymph node status for colon cancer staging and prognosis.

Abstract

PURPOSE:

The prognostic significance of guanylyl cyclase C (GCC) gene expression in lymph nodes (LNs) was evaluated in patients with stage II colon cancer who were not treated with adjuvant chemotherapy. We report a planned analysis performed on 241 patients.

METHODS:

GCC mRNA was quantified by RT-qPCR using formalin-fixed LN tissues from patients with untreated stage II colon cancer who were diagnosed from 1999-2006 with at least ten LNs examined and blinded to clinical outcomes. Lymph node ratio (LNR) is the number of GCC-positive nodes divided by total number of informative LNs. Risk categories of low (0-0.1) and high (>0.1) for LNR were chosen by significance using Cox regression models. The data were tested for association with time to recurrence.

RESULTS:

Twenty-nine patients (12%) had a disease recurrence or cancer death. The LNR significantly predicted higher recurrence risk for 84 patients (34.9%) classified as high risk (hazard ratio (HR), 2.38; P=0.02). The estimated 5-year recurrence rates were 10% and 27% for the low- and high-risk groups, respectively. After adjusting for age, T stage, number of nodes assessed, and MMR status, a significant association remained (HR, 2.61; P=0.02). In a subset of patients (n=181) with T3 tumor, ≥12 nodes examined and negative margins, a significant association between the GCC LNR and recurrence risk also was observed (HR, 5.06; P=0.003).

CONCLUSIONS:

Our preliminary results suggest that detection of GCC mRNA in LNs is associated with risk of disease recurrence in patients with untreated stage II colon cancer. A larger validation study is ongoing.

• Authors: Daniel J Sargent, Murray B Resnick, Michael O Meyers, Atoussa Goldar-Najafi, Thomas Clancy, Sharlene Gill, Gary O Siemons, Qian Shi, Brian M Bot, Tsung-Teh Wu, Guillaume Beaudry, Jean-François Haince, Yves Fradet
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 18 Issue 12 Pg. 3261-70 (Nov 2011) ISSN: 1534-4681 [Electronic] United States
• PMID: 21533822 (Publication Type: Journal Article)

Chemical References

• RNA, Messenger
• Receptors, Peptide
• Guanylate Cyclase
• Receptors, Enterotoxin
• Receptors, Guanylate Cyclase-Coupled

Topics

• Adult
• Aged
• Aged, 80 and over
• Colonic Neoplasms (enzymology, genetics, pathology)
• Female
• Follow-Up Studies
• Guanylate Cyclase (genetics)
• Humans
• Lymph Nodes (pathology)
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Recurrence, Local (diagnosis, enzymology, genetics)
• Neoplasm Staging
• Prognosis
• Prospective Studies
• RNA, Messenger (genetics)
• Receptors, Enterotoxin
• Receptors, Guanylate Cyclase-Coupled (genetics)
• Receptors, Peptide (genetics)
• Retrospective Studies
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate