A prospective multicenter study of guanylyl cyclase C (GCC), quantified by the reverse transcriptase-polymerase chain reaction (qRT-PCR), as a prognostic marker of occult metastases in lymph nodes of pN0 colorectal cancer patients.
11011 Background: Patients with pN0 colorectal cancer have a ∼25% risk of disease recurrence reflecting, in part, under-diagnosis of lymph node metastases at staging. Improved methods that predict recurrence would identify patients who could benefit from adjuvant chemotherapy. GCC, expressed selectively by intestinal cells and universally in colorectal tumors, is a marker whose detection in lymph nodes could enhance staging. METHODS: At staging, 356 patients with pN0 colorectal cancer from 9 hospitals were enrolled. Fresh lymph nodes >5 mm were bisected for histopathology and GCC qRT-PCR. Three hundred patients provided lymph nodes, of which 261 provided tissues with sufficient mRNA for analysis. Categorical GCC expression, normalized to beta-actin, was estimated in 2,452 lymph nodes from these patients, who were followed to assess time to recurrence. RESULTS: Median follow-up of patients was 45 months (range 1-75 months). Of the 261 patients, 13% (34 patients) had lymph nodes free of occult metastases by GCC qRT-PCR and all but 2 remained free of disease (5.8% raw recurrence rate). Conversely, 20.7% (47 patients) with lymph nodes containing occult metastases by GCC qRT-PCR developed recurrent disease (p=0.029, log-rank test). In multivariable Cox models, controlling for T stage, tumor location, lymphovascular invasion, and tumor differentiation, occult metastases in lymph nodes by GCC qRT-PCR was the most powerful independent predictor of recurrence (adjusted Hazard Ratio=4.51, p=0.039, 95%CI=1.07, 18.90). CONCLUSIONS: GCC qRT-PCR identifies occult metastases in lymph nodes that independently predict time to recurrence in pN0 colorectal cancer patients. Thus, GCC may serve as a prognostic and predictive marker, identifying pN0 patients at minimum risk for disease recurrence and, conversely, who might benefit from adjuvant chemotherapy, respectively. [Table: see text].
Waldman, SA; Hyslop, T; Schulz, S; Nielsen, K; Haaf, J; Bonaccorso, C; Li, Y; Barkun, A; Weinberg, D
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