Guanylyl cyclase C (GCC) expression in lymph nodes (LNs) as a determinant of recurrence in stage II colon cancer (CC) patients (pts).

Gastrointestinal (Colorectal) Cancer
Session Type and Session Title: 
General Poster Session, Gastrointestinal (Colorectal) Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 3639)
Daniel J. Sargent, Qian Shi, Sharlene Gill, Christophe Louvet, Richard Bernard Everson, Udo Kellner, Thomas E. Clancy, J. Marc Pipas, Murray B. Resnick, Michael O. Meyers, David Huntsman, Pierre Validire, Umar Farooq, Emily S Pavey, Jean-Francois Haince, Guillaume Beaudry, Yves Fradet; Mayo Clinic, Rochester, MN; British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Oncology, Institut Mutualiste Montsouris, Paris, France; University of Connecticut Health Center, Farmington, CT; Johannes Wessling Klinikum Minden, Minden, Germany; Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Rhode Island Hospital; Brown University, Providence, RI; Division of Surgical Oncology and Endocrine Surgery, University of North Carolina School of Medicine, Chapel Hill, NC; Department of Pathology, Institut Mutualiste Montsouris, Paris, France; DiagnoCure Inc., Quebec, QC, Canada

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: The first phase of the multi-center prospectively specified retrospective study Validating Indicators To Associate Recurrence (VITAR), assessing the relationship between GCC gene expression in formalin fixed (FFPE) LNs and time to recurrence (TTR) in stage II CC pts not treated with adjuvant chemotherapy (Sargent, Annals Surg Onc 2011), showed promising initial results. Here we report a validation set of 463 new stage II CC pts. Methods: GCC mRNA was quantified by RT-qPCR using FFPE LNs from untreated T3N0 CC pts diagnosed from 1999-2008 with at least 12 LNs examined , blinded to clinical outcomes. Patients were classified by GCC LN ratio (LNR) (high risk: LNR > 0.1; low risk: LNR ≤ 0.1), with LNR defined as ratio of GCC positive to GCC informative LNs. Cox regression models tested the relationship between GCC and the primary endpoint of TTR, adjusted for age, tumor grade, number of LN examined pathologically, and lymphovascular invasion. Mismatch repair (MMR) status was also assessed. All primary analyses and cut-points were pre-specified. Results: 46pts (10%) recurred (rec), median follow-up was 65 months, median LNs examined was 20, and 42% (195/463) were classified high risk. Overall, TTR was not significantly associated with binary GCC LNR risk class (HR=1.47, p=.208) or DFS (HR= 1.39, p=.097). One site’s (n=97) tissue grossing method precluded appropriate LN assessment with existing GCC qualification methods. Excluding this site resulted in a TTR HR=1.91, p=0.051 (multivariate). In a post-hocanalysis excluding this site and using a 3-level GCC risk group of high (LNR > 0.20), intermediate (0.10 < LNR < 0.20) and low (LNR < 0.10), high risk group pts had a 5-yr rec risk of 22% versus 8% in low risk (HR 2.72, p=0.006). MMR status was not significantly associated with TTR (multivariate p=0.30). Conclusions: GCC status is a promising prognostic factor in appropriately staged stage II CC pts not treated with adjuvant therapy independent of traditional histopathology risk factors, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique. Outcome associations were strengthened when considering a 3-level GCC categorization.