Association of GUCY2C Expression in Lymph Nodes With Time to Recurrence and Disease-Free Survival in pN0 Colorectal Cancer

Waldman, Scott A.

doi:10.1001/jama.2009.141

Cited by 103 publications

(232 citation statements)

References 42 publications

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“…With IHC and molecular genetics methods, occult tumor cells in regional lymph nodes are detected in 25% to 50% of patients with node-negative colorectal cancer (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Because up to 25% of patients with node-negative colorectal cancer ultimately die as a result of disease relapse, occult cancer metastasis has been suspected as a potential marker for systemic spread of tumor cells (1).…”

Section: Introductionmentioning

confidence: 99%

“…Because up to 25% of patients with node-negative colorectal cancer ultimately die as a result of disease relapse, occult cancer metastasis has been suspected as a potential marker for systemic spread of tumor cells (1). However, the prognostic value of molecular tumor cell detection in patients with node-negative colorectal cancer has remained uncertain because of lack of evidence from prospective studies (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

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Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial

Yamamoto

Murata

Fukunaga

et al. 2016

Clinical Cancer Research

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Purpose: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial.Experimental Design: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method.Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n ¼ 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P ¼ 0.001) and 5-year overall survival (OS; P ¼ 0.016).Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial

Yamamoto

Murata

Fukunaga

et al. 2016

Clinical Cancer Research

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“…The selective expression of GCC in colorectal tumor cells at metastatic sites (Carrithers et al, 1994(Carrithers et al, , 1996Waldman et al, 1998), suggests its utility as a diagnostic marker and specific target for delivering imaging and therapeutic agents in vivo (Gali et al, 2001;Wolfe et al, 2002). Indeed, clinical trials are confirming the value of GCC as a diagnostic marker for molecular staging of patients and prognostic indicator of colorectal cancer recurrence (Mejia et al, 2010;Waldman et al, 2009). Moreover, the structural preservation of GCC and its intracellular effectors offers the GCC hormone replacement therapy as a novel clinical paradigm for the prevention and treatment of colorectal cancer .…”

Section: The Gcc Pathway As a Source Of Novel Clinical Targetsmentioning

confidence: 95%

Emergent Concepts from the Intestinal Guanylyl Cyclase C Pathway

Ali¹,

Pitari²

2012

Colorectal Cancer Biology - From Genes to Tumor

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“…GCC is a human receptor for the gastrointestinal hormones, guanylin and uroguanylin, normally found in the luminal aspect of intestinal epithelium and whose expression is preserved in primary and metastatic colorectal cancer cells (11). Preliminary studies have suggested that the presence of GCC mRNA expression in lymph nodes increases the likelihood of colon cancer recurrence, independently of traditional high-risk features (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Molecular Testing for Lymph Node Metastases as a Determinant of Colon Cancer Recurrence: Results from a Retrospective Multicenter Study

Sargent¹,

Gill

Louvet³

et al. 2014

Clinical Cancer Research

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Purpose: Recurrence risk assessment to make treatment decisions for early-stage colon cancer patients is a major unmet medical need. The aim of this retrospective multicenter study was to evaluate the clinical utility of guanylyl cyclase C (GCC) mRNA levels in lymph nodes on colon cancer recurrence.Methods: The proportion of lymph nodes with GCC-positive mRNA (LNR) was evaluated in 463 untreated T3N0 patients, blinded to clinical outcomes. One site's (n ¼ 97) tissue grossing method precluded appropriate lymph node assessment resulting in post hoc exclusion. Cox regression models tested the relationship between GCC and the primary endpoint of time to recurrence. Assay methods, primary analyses, and cut points were all prespecified.Results: Final dataset contained 366 patients, 38 (10%) of whom had recurrence. Presence of four or more GCC-positive lymph nodes was significantly associated with risk of recurrence [hazard ratio (HR) ¼ 2.46, 95% confidence interval (CI), 1.07-5.69, P ¼ 0.035], whereas binary GCC LNR risk class (HR ¼ 1.87, 95% CI, 0.99-3.54, P ¼ 0.054) and mismatch repair (MMR) status (HR ¼ 0.77, 95% CI, 0.36-1.62, P ¼ 0.49) were not. In a secondary analysis using a 3-level GCC LNR risk group classification of high (LNR > 0.20), intermediate (0.10 < LNR 0.20), and low (LNR 0.10), high-risk patients had a 2.5 times higher recurrence risk compared with low-risk patients (HR ¼ 2.53, 95% CI, 1.24-5.17, P ¼ 0.011).Conclusions: GCC status is a promising prognostic factor independent of traditional histopathology risk factors in a contemporary population of patients with stage IIa colon cancer not treated with adjuvant therapy, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique.

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Association of GUCY2C Expression in Lymph Nodes With Time to Recurrence and Disease-Free Survival in pN0 Colorectal Cancer

Cited by 103 publications

References 42 publications

Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial

Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial

Emergent Concepts from the Intestinal Guanylyl Cyclase C Pathway

Molecular Testing for Lymph Node Metastases as a Determinant of Colon Cancer Recurrence: Results from a Retrospective Multicenter Study

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