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Molecular testing for lymph node metastases as a determinant of colon cancer recurrence: results from a retrospective multicenter study.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2014 Aug 15; Vol. 20 (16), pp. 4361-9. Date of Electronic Publication: 2014 Jun 11. - Publication Year :
- 2014
-
Abstract
- 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.<br />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 = 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.<br />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) = 2.46, 95% confidence interval (CI), 1.07-5.69, P = 0.035], whereas binary GCC LNR risk class (HR = 1.87, 95% CI, 0.99-3.54, P = 0.054) and mismatch repair (MMR) status (HR = 0.77, 95% CI, 0.36-1.62, P = 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 = 2.53, 95% CI, 1.24-5.17, P = 0.011).<br />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.<br /> (©2014 American Association for Cancer Research.)
- Subjects :
- Adenocarcinoma enzymology
Adenocarcinoma mortality
Adult
Aged
Aged, 80 and over
Colonic Neoplasms enzymology
Colonic Neoplasms mortality
Female
Follow-Up Studies
Humans
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Recurrence, Local enzymology
Neoplasm Recurrence, Local mortality
Neoplasm Staging
Prognosis
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Receptors, Enterotoxin
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate
Adenocarcinoma secondary
Biomarkers, Tumor genetics
Colonic Neoplasms pathology
Neoplasm Recurrence, Local pathology
Receptors, Guanylate Cyclase-Coupled genetics
Receptors, Peptide genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 20
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 24919572
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-13-2659