Annals of Surgical Oncology

, Volume 18, Issue 12, pp 3261–3270 | Cite as

Evaluation of Guanylyl Cyclase C Lymph Node Status for Colon Cancer Staging and Prognosis

  • 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
Colorectal Cancer

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.

Keywords

Overall Survival Lymph Node Ratio Recurrence Risk Guanylyl Cyclase Colon Cancer Recurrence 

Notes

Acknowledgment

The authors thank Marie Desaulniers and Danielle Allard for critical reading of this manuscript. They also thank Michel Houde for his involvement in the conception and design of the study as well as the staff from BC Cancer Agency Laboratory for the preparation of their tissues and DiagnoCure personnel for their contribution to this study.

Conflict of interest

The authors have no other potential conflict of interest to declare.

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Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Daniel J. Sargent
    • 1
  • Murray B. Resnick
    • 2
  • Michael O. Meyers
    • 3
  • Atoussa Goldar-Najafi
    • 4
  • Thomas Clancy
    • 5
  • Sharlene Gill
    • 6
  • Gary O. Siemons
    • 7
  • Qian Shi
    • 1
  • Brian M. Bot
    • 1
  • Tsung-Teh Wu
    • 8
  • Guillaume Beaudry
    • 9
  • Jean-François Haince
    • 9
  • Yves Fradet
    • 9
  1. 1.Division of Biomedical Statistics and InformaticsMayo ClinicRochesterUSA
  2. 2.Alpert Medical SchoolBrown University and Rhode Island HospitalProvidenceUSA
  3. 3.Division of Surgical OncologyThe University of North CarolinaChapel HillUSA
  4. 4.Department of PathologyLahey Clinic Gordon Cancer CenterBurlingtonUSA
  5. 5.Division of Surgical OncologyBrigham and Women’s Hospital and Dana-Farber Cancer InstituteBostonUSA
  6. 6.Division of Medical OncologyUniversity of British Columbia, BC Cancer AgencyVancouverCanada
  7. 7.Colon and Rectal Surgical Associates of South JerseyVoorheesUSA
  8. 8.Department of Anatomic PathologyMayo ClinicRochesterUSA
  9. 9.DiagnoCure IncQuébecCanada

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