High matrix metalloproteinase-to-E-cadherin ratio measured by bicolor fluorescent in situ hybridization is associated with lymphangiogenesis and lymph node metastasis in prostate cancer.
OBJECTIVE
The colorimetric in situ hybridization (CISH)-based matrix metalloproteinase (MMP)-to-E-cadherin (ECD) ratio (MER) has been revealed as an excellent marker for the disease stage in prostate cancer. The one aim of this study was investigating a new method for estimation of MER by bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector-based system. Another aim was examination of relation of MER by bicolor FISH with expression of vascular endothelial growth factor-C (VEGF-C).


METHODS
The bicolor FISH technique used cyanin 5 (cy5)-labeled MMP-2 and -9 probes, and a cyanin 3 (cy3)-labeled ECD probe on needle biopsy specimens from 67 prostate cancer cases. The ISH was followed by computerized detection of the signal intensities and cy5-to-cy3 ratios using a fluorescence detector. VEGF-C expression was examined using cy5-labeled VEGF-C by computerized detection.


RESULTS
The bicolor FISH-based MER was well correlated with CISH-based MER (P < 0.0001). The bicolor FISH-based MER correlated with Gleason score and pathologic stage of the cases. VEGF-C mRNA expression was associated with the pathologic stage and maximum lymph vessel density (LVD). The LVD was associated with VEGF-C expression at the tumor area where the maximum MER was detected (P < 0.0001).


CONCLUSIONS
The MER was correlated with the VEGF-C expression and LVD, indicating lymph node metastasis of prostate cancer. Therefore, this computer-assisted MER is a useful marker for preoperative prediction of disease stage, especially lymph node metastasis, of prostate cancer.
Luo
Yi
Y
Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
Ohmori
Hitoshi
H
Fujii
Kiyomu
K
Chihara
Yoshitomo
Y
Maruyama
Satoshi
S
Kuniyasu
Hiroki
H
D001706:Biopsy / Q000379:methods; D001707:Biopsy, Needle / Q000379:methods; D015820:Cadherins / Q000096:biosynthesis*; D002232:Carbocyanines / Q000494:pharmacology; D018450:Disease Progression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008495:Medical Oncology / Q000379:methods; D009362:Neoplasm Metastasis; D015345:Oligonucleotide Probes / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
D015820:Cadherins; D002232:Carbocyanines; D015345:Oligonucleotide Probes; D042582:Vascular Endothelial Growth Factor C; C089187:cyanine dye 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9