Melanoma-Associated Antigen (MAGE) Expression in the Normal Mucosa around Colorectal Cancer after Curative Resection: Presence of Undetectable Free Cancer Cells?
Free accessResearch articleFirst published online April, 2011
Melanoma-Associated Antigen (MAGE) Expression in the Normal Mucosa around Colorectal Cancer after Curative Resection: Presence of Undetectable Free Cancer Cells?
Curative surgical resection is of great importance and some trials have been performed to identify free undetectable cancer cells using molecular markers. The aim of this study is to investigate melanoma-associated antigen (MAGE) expression in normal mucosa around colorectal cancer and its clinical significance.
Material and method
From October 2003 to June 2004, we collected 46 colorectal cancer and matched normal mucosal tissues within 20 mm, 20 to 50 mm and more than 50 mm from tumors after the curative operation. Twenty-two mucosal tissues were harvested from patients with benign colorectal diseases as controls. MAGE expression was assayed using nested RT-PCR of MAGE A1-6 mRNA.
Results
The MAGE expression rates in cancer tissue and adjacent normal mucosa were 65.2%, 6.5% (<20 mm), 2.2% (20–50 mm) and 0.0% (>50 mm), respectively, while MAGE was not expressed in the mucosa of benign diseases. The MAGE-positive cases in the normal mucosa around tumors were located in the left colon or rectum, and one patient showed anastomotic mucosal site recurrence.
Conclusions
MAGE expression in normal-appearing mucosa around colorectal cancer showed some clinical findings suggesting the presence of undetectable free cancer cells after curative resection.
WonY.J., SungJ., JungK.W.Nationwide cancer incidence in Korea, 2003–2005.Cancer Res Treat2009; 41: 122–31.
2.
AbulafiA.M., WilliamsN.S.Local recurrence of colorectal cancer: the problem, mechanisms, management and adjuvant therapy.Br J Surg1994; 81: 7–19.
3.
KyzerS., MitmakerB., GordonP.H., SchipperH., WangE.Proliferative activity of colonic mucosa at different distances from primary adenocarcinoma as determined by the presence of statin: a nonproliferation-specific nuclear protein.Dis Colon Rectum1992; 35: 879–83.
4.
PandeyS., GordonP.H., WangE.Expression of proliferation-specific genes in the mucosa adjacent to colon carcinoma.Dis Colon Rectum1995; 38: 462–7.
5.
Van der BruggenP., TraversariC., ChomezP.A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma.Science1991; 254: 1643–7.
6.
Van den EyndeB.J., van der BruggenP.T cell defined tumor antigens.Curr Opin Immunol1997; 9: 684–93.
7.
KirkinA.F., DzhandzhugazyanK., ZeuthenJ.Melanoma-associated antigens recognized by cytotoxic T lymphocytes.APMIS1998; 106: 665–79.
8.
KienstraM.A., NeelH.B., StromeS.E., RocheP.Identification of NY-ESO-1, MAGE-1, and MAGE-3 in head and neck squamous cell carcinoma.Head Neck2003; 25: 457–63.
9.
YakirevichE., SaboE., LavieO., MazarebS., SpagnoliG.C., ResnickM.B.Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens in serous ovarian neoplasms.Clin Cancer Res2003; 9: 6453–60.
10.
KocherT., ZhengM., BolliM.Prognostic relevance of MAGE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study.Int J Cancer2002; 100: 702–5.
11.
JheonS., HyunD.S., LeeS.C.Lung cancer detection by a RT-nested PCR using MAGE A1-6 common primers.Lung Cancer2004; 43: 29–37.
12.
LiM., YuanY.H., HanY.Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue.Clin Cancer Res2005; 11: 1809–14.
13.
ChomezP., De BackerO., BertrandM., De PlaenE., BoonT., LucasS.An overview of the MAGE gene family with the identification of all human members of the family.Cancer Res2001; 61: 5544–51.
14.
JungbluthA.A., BusamK.J., KolbD.Expression of MAGE-antigens in normal tissues and cancer.Int J Cancer2000; 85: 460–5.
15.
RiesJ., Schultze-MosgauS., NeukamF., DiebelE., WiltfangJ.Investigation of the expression of melanoma antigen-encoding genes (MAGE-A1 to -A6) in oral squamous cell carcinomas to determine potential targets for gene-based cancer immunotherapy.Int J Oncol2005; 26: 817–24.
16.
BrichardV.G., JejeuneD.GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development.Vaccine2007: 25: 61–71.
17.
HofmannM., RuschenburgI.mRNA detection of tumor-rejection genes BAGE, GAGE, and MAGE in peritoneal fluid from patients with ovarian carcinoma as a potential diagnostic tool.Cancer2002; 96: 187–93.
18.
ParkJ.W., KwonT.K., KimI.H.A new strategy for the diagnosis of MAGE-expressing cancers.J Immunol Methods2002; 266: 79–86.
19.
ConzelmannM., LinnemannU., BergerM.R.Molecular detection of clinical colorectal cancer metastasis: how should multiple markers be put to use?Int J Colorectal Dis2005; 20: 137–46.
20.
HarrisG.J., ChurchJ.M., SenagoreA.J.Factors affecting local recurrence of colonic adenocarcinoma.Dis Colon Rectum2002; 45: 1029–34.
21.
ThomsonW.H., FoyC.J., LongmanR.J.The nature of local recurrence after colorectal cancer resection.Colorectal Dis2008; 10: 69–74.
22.
ParkM.S., ParkJ.W., JeonC.H., LeeK.D., ChangH.K.Expression of melanoma antigen-encoding genes (MAGE) by common primers for MAGE-A1 to -A6 in colorectal carcinomas among Koreans.J Korean Med Sci2002; 17: 497–501.
23.
GerhardtA., UsenerD., KeeseM., SturmJ., SchadendorfD., EichmullerS.Tissue expression and sero-reactivity of tumor-specific antigens in colorectal cancer.Cancer Lett2004; 208: 197–206.
24.
NgoiS.S., Staiano-CoicoL., GodwinT.A., WongR.J., DeCosseJ.J.Abnormal DNA ploidy and proliferative patterns in superficial colonic epithelium adjacent to colorectal cancer.Cancer1990; 66: 953–9.
25.
AivadoM., GynesM., GorelovV., SchmidtW.U., RoherH.D., GoretzkiP.E.“Field cancerization” an additional phenomenon in development of colon tumors? K-ras codon 12 mutations in normal colonic mucosa of patients with colorectal neoplasm.Chirurg2000; 71: 1230–4.
26.
AndreolaS., LeoE., BelliF.Distal intramural spread in adenocarcinoma of the lower third of the rectum treated with total rectal resection and coloanal anastomosis.Dis Colon Rectum1997; 40: 25–9.
27.
PanZ.Z., WanD.S., ZhangC.Q.Clinical significance of P53-immuno-histochemistry in large slice in evaluating distal intramural spread extent in rectal cancer.Ai Zheng2004; 23: 1199–202.
28.
SayfanJ., AverbuchF., KoltunL., BenyaminN.Effect of rectal stump washout on the presence of free malignant cells in the rectum during anterior resection for rectal cancer.Dis Colon Rectum2000; 43: 1710–2.
