Comparison of histopathology and RT-qPCR amplification of guanylyl cyclase C for detection of colon cancer metastases in lymph nodes
- Jean-François Haince1,
- Michel Houde1,
- Guillaume Beaudry1,
- Sylvain L'Espérance1,
- Geneviève Garon1,
- Marie Desaulniers1,
- Laurie J Hafer1,2,
- James I Heald1,2,
- Stephen Lyle3,
- Steven R Grossman3,
- Bernard Têtu4,
- Daniel J Sargent5,
- Yves Fradet1,6
- 1DiagnoCure Inc., Québec, Canada
- 2DiagnoCure Oncology Laboratories, West Chester, Pennsylvania, USA
- 3Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
- 4Department of Pathology and Research Center, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Laval University, Canada
- 5Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
- 6Department of Urology, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Laval University, Canada
- Correspondence to Dr Jean-François Haince, DiagnoCure Inc., 2050 René-Lévesque Blvd. West, 6th Floor, Québec, Qc, G1V 2K8 Canada;
- Accepted 18 February 2010
Aims In colorectal cancer (CRC), the presence of lymph node (LN) metastases is an important prognostic factor. Approximately 20% of patients diagnosed as having node-negative (pN0) CRC will relapse. Pathological nodal stage misclassification due to sampling error resulting from the small volume of tissue tested has been proposed to explain this recurrence rate in pN0 patients. The authors compared the assessment of node positivity by histopathology (HP) with a molecular method which can accommodate larger tissue volumes.
Methods Detection rate of guanylyl cyclase C (GCC) mRNA was determined in 1495 LNs from 99 CRC patients. Using a subset of 647 LNs, multiple levels of HP analysis were compared with GCC mRNA molecular detection. Finally, clinicopathological factors were correlated with the molecular detection of GCC and clinical outcome in 123 patients with pN0 colon cancer.
Results GCC mRNA was detected in 8.0% of the 560 nodes initially identified as HP-negative, whereas two repeat HP examinations detected 3.0% of these cases. In HP-positive LNs, the GCC mRNA detection rate was 90% (78/87) when half-LN were tested. Testing the entire LN remaining after HP by GCC increased the detection rate of HP-positive LNs to 95% (p=0.027). In comparison, 75% (65/87) and 92% (80/87) of the LN positive by clinical HP remained positive when one or two subsequent sections were examined by HP. Finally, patients with pN0 disease who were GCC-positive exhibited an earlier time of recurrence (hazard ratio, 3.54; 95% CI 1.40 to 8.98; p=0.0077).
Conclusions Molecular detection of tumour cells in LNs may have prognostic value in identifying patients diagnosed as having pN0 colon cancer who will relapse following surgery.
- colorectal cancer
- molecular diagnosis
- detection of occult metastasis
- molecular pathology
Competing interests BT and DJS are paid consultants for Diagnocure Inc.
Ethics approval Ethics approval was provided by l'Hotel-Dieu de Québec, Centre Hospitalier Universitaire de Québec and University of Massachusetts Medical School.
Provenance and peer review Not commissioned; externally peer reviewed.