Discordant quantitative detection of putative biomarkers in nodal micrometastases of colorectal cancer: biological and clinical implications.
OBJECTIVE
Nodal expression of the carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), and guanylyl cyclase C (GCC) genes was measured in tandem in patients with colorectal cancer (CRC) to assess whether there would be sufficient agreement between these markers in their ability to detect micrometastasis to qualify one of them as a universal marker, and whether frozen and paraffin wax embedded tissues would yield similar results.


METHODS
One hundred and seventy five frozen lymph nodes (FT) and 158 formalin fixed, paraffin wax embedded lymph nodes (PET) from 28 CRC cases were analysed using gene specific quantitative real time polymerase chain reaction, carried out on the LightCycler system with SYBR Green chemistry.


RESULTS
There was significant disparity in positive detection of the three biomarkers in FT versus PET, with notable agreement achieved only for CEA (66.6%) in FT versus PET in Dukes' B disease, and between CK20 and GCC (44.6%) in FT, also in Dukes' B disease. One patient with full concordance in all three tumour markers with both tissue types suffered a relapse and died within two years of follow up.


CONCLUSIONS
There was considerable discordance in the positive detection of the three tumour markers in both tissue types (FT versus PET). This brings into question whether using a single tumour marker to detect micrometastasis in one tissue type (FT or PET) is adequately representative, and challenges the concept of universal markers for molecular CRC metastatic detection. Multiple tumour markers would predict more accurately the metastatic potential of Dukes' B CRCs.
Kong
S L
SL
Department of Pathology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260.
Salto-Tellez
M
M
Leong
A P K
AP
Chan
Y H
YH
Koay
E S C
ES
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015925:Cryopreservation; D015870:Gene Expression; D006162:Guanylate Cyclase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis / Q000235:genetics; D053554:Keratin-20; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D006162:Guanylate Cyclase