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Lymph node CEA and MUC2 mRNA as useful predictors of outcome in colorectal cancer

Ohlsson, Lina; Israelsson, Anne; Oberg, Ake; Palmqvist, Richard; Stenlund, Hans; Hammarstrom, Marie-Louise; Hammarstrom, Sten and Lindmark, Gudrun LU (2012) In International Journal of Cancer 130(8). p.1833-1843
Abstract
The aim was to explore the utility for staging and prognostic impact of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), guanylyl cyclase C (GCC), CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor, and bone morphogenic protein 1) containing domain protein 1 (CDCP1) and mucin 2 (MUC2) mRNA levels in mesenteric lymph nodes of colorectal cancer (CRC) patients. Lymph nodes were collected at surgery and bisected; one half was subjected to biomarker mRNA analysis using real-time quantitative RT-PCR and the other half to routine histopathology. Lymph nodes from 174 CRC patients and 24 controls were analyzed. The median follow-up time was 59 (range 17-131) months. Cut-off levels were defined by analyzing quintiles... (More)
The aim was to explore the utility for staging and prognostic impact of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), guanylyl cyclase C (GCC), CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor, and bone morphogenic protein 1) containing domain protein 1 (CDCP1) and mucin 2 (MUC2) mRNA levels in mesenteric lymph nodes of colorectal cancer (CRC) patients. Lymph nodes were collected at surgery and bisected; one half was subjected to biomarker mRNA analysis using real-time quantitative RT-PCR and the other half to routine histopathology. Lymph nodes from 174 CRC patients and 24 controls were analyzed. The median follow-up time was 59 (range 17-131) months. Cut-off levels were defined by analyzing quintiles by Cox regression model. CEA mRNA showed the best discriminating power between patients with recurrence in CRC after surgery and patients who were apparently disease-free (p = 0.015). The risk of recurrence for the CEA(+) patients was 4.6 times greater than for the CEA(-) patients (p < 0.0001). The other biomarkers gave lower hazard ratios. Cumulative survival analysis demonstrated that the average survival time was 99 months for CEA(-) patients compared to 39 months for CEA(+) patients, a difference of 60 months (p < 0.0001). Six to nine percent of the Stage I and Stage II patients [H&E(-)] had CEA(+), CK20(+), GCC(+) and/or MUC2(+) lymph nodes. Two of these patients died from recurrent CRC. Low lymph node MUC2/CEA mRNA ratio identified patients with high risk for recurrence (p = 0.011). Thus, quantitative reverse transcriptase-polymerase chain reaction of CEA mRNA is a sensitive method to identify tumor cells in lymph nodes of CRC patients and, in combination with MUC2 mRNA, allows improved prediction of clinical outcome. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
colorectal neoplasms, lymphatic metastasis, neoplasm staging, prognosis, qRT-PCR
in
International Journal of Cancer
volume
130
issue
8
pages
1833 - 1843
publisher
John Wiley & Sons
external identifiers
  • wos:000300692300013
  • scopus:84857505150
ISSN
0020-7136
DOI
10.1002/ijc.26182
language
English
LU publication?
yes
id
0fee59da-56c5-4cc1-9be3-ba2dd5e14cbf (old id 2378728)
date added to LUP
2012-04-02 09:20:33
date last changed
2017-01-01 04:11:28
@article{0fee59da-56c5-4cc1-9be3-ba2dd5e14cbf,
  abstract     = {The aim was to explore the utility for staging and prognostic impact of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), guanylyl cyclase C (GCC), CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor, and bone morphogenic protein 1) containing domain protein 1 (CDCP1) and mucin 2 (MUC2) mRNA levels in mesenteric lymph nodes of colorectal cancer (CRC) patients. Lymph nodes were collected at surgery and bisected; one half was subjected to biomarker mRNA analysis using real-time quantitative RT-PCR and the other half to routine histopathology. Lymph nodes from 174 CRC patients and 24 controls were analyzed. The median follow-up time was 59 (range 17-131) months. Cut-off levels were defined by analyzing quintiles by Cox regression model. CEA mRNA showed the best discriminating power between patients with recurrence in CRC after surgery and patients who were apparently disease-free (p = 0.015). The risk of recurrence for the CEA(+) patients was 4.6 times greater than for the CEA(-) patients (p &lt; 0.0001). The other biomarkers gave lower hazard ratios. Cumulative survival analysis demonstrated that the average survival time was 99 months for CEA(-) patients compared to 39 months for CEA(+) patients, a difference of 60 months (p &lt; 0.0001). Six to nine percent of the Stage I and Stage II patients [H&amp;E(-)] had CEA(+), CK20(+), GCC(+) and/or MUC2(+) lymph nodes. Two of these patients died from recurrent CRC. Low lymph node MUC2/CEA mRNA ratio identified patients with high risk for recurrence (p = 0.011). Thus, quantitative reverse transcriptase-polymerase chain reaction of CEA mRNA is a sensitive method to identify tumor cells in lymph nodes of CRC patients and, in combination with MUC2 mRNA, allows improved prediction of clinical outcome.},
  author       = {Ohlsson, Lina and Israelsson, Anne and Oberg, Ake and Palmqvist, Richard and Stenlund, Hans and Hammarstrom, Marie-Louise and Hammarstrom, Sten and Lindmark, Gudrun},
  issn         = {0020-7136},
  keyword      = {colorectal neoplasms,lymphatic metastasis,neoplasm staging,prognosis,qRT-PCR},
  language     = {eng},
  number       = {8},
  pages        = {1833--1843},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Lymph node CEA and MUC2 mRNA as useful predictors of outcome in colorectal cancer},
  url          = {http://dx.doi.org/10.1002/ijc.26182},
  volume       = {130},
  year         = {2012},
}