Multiparametric in situ messenger RNA hybridization analysis to detect metastasis-related genes in surgical specimens of human colon carcinomas.
We examined the expression of several genes that regulate different steps of metastasis in surgical specimens of human colon carcinomas. The expression of epidermal growth factor receptor (growth), basic fibroblast growth factor [(bFGF), angiogenesis], type IV collagenase (invasion), E-cadherin (adhesion), and multidrug-resistant (mdr)-1 (drug resistance) mRNA was examined using an in situ mRNA hybridization (ISH) technique and Northern blot analysis. Dukes' stage C and D tumors exhibited a higher level of expression (P <0.05) for bFGF, type IV collagenase, and mdr-1 mRNA than Dukes' stage B tumors. The expression level of epidermal growth factor receptor and E-cadherin did not correlate with the stage of the disease. The ISH technique revealed intertumoral heterogeneity for expression of several genes among Dukes' stage B neoplasms. In some Dukes' stage B tumors, we also found intratumoral heterogeneous staining for bFGF and type IV collagenase, with the highest expression level at their invasive edge. In Dukes' stage C and D tumors, the expression of these genes was more uniform. These results recommend the suitability of the multiparametric ISH analysis for metastasis-related genes to identify individual colon cancers with metastatic potential.
Kitadai
Y
Y
Departments of Cell Biology and Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Ellis
L M
LM
Takahashi
Y
Y
Bucana
C D
CD
Anzai
H
H
Tahara
E
E
Fidler
I J
IJ
D015152:Blotting, Northern; D015820:Cadherins / Q000235:genetics; D017364:Collagenases / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression; D019450:Genes, MDR; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D009362:Neoplasm Metastasis / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*
D015820:Cadherins; D009363:Neoplasm Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016222:Fibroblast Growth Factor 2; D066246:ErbB Receptors; D017364:Collagenases