High frequency of concomitant nm23-H1 and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas.
This study evaluated the added significance of nm23-H1 to that of E-cadherin in determining metastatic proclivity in primary sporadic colorectal carcinomas (SCRCs). A clinical cohort of 52 SCRCs was examined for the significance of nm23-H1 and E-cadherin mRNA levels and E-cadherin protein expression levels into the progression of colorectal tumor invasion, determined by their relevance compared with conventional biological markers. A more than twofold decreased expression of nm23-H1 mRNA was reported in 28/52 (54%) of the carcinomas and was positively associated with the presence of nodal metastases and Astler-Coller stages B1 and B2 in 29% and 35% of the SCRCs, respectively. Reduced expression of E-cadherin mRNA was reported in 38.5% of the carcinomas and was similarly associated with stages Astler-Coller B1 and B2 in 27% of the SCRCs. Decreased E-cadherin immunohistochemical expression (grades II and III) was observed in 67% of the samples. E-cadherin mRNA and protein expression were significantly related to each other. The nm23-H1 (+)/E-cadherin (+) coexpression profile was observed in 31% and was significantly related to the absence of lymph node metastases in 31% and stages Astler-Coller B1 and B2 in 29% of the carcinomas examined. Furthermore, the nm23-H1 (-)/E-cadherin (+) coexpression profile was coupled to decreased E-cadherin immunohistochemical protein detection (grade II) in 21% of the cases examined. These findings suggest that impairment of nm23-H1 expression is an early event into the progression of colorectal metastasis that precedes E-cadherin transcriptional silencing in the majority of SCRCs examined. Nm23-H1 may therefore play an important role in suppressing the early steps of metastasis in sporadic cases of colorectal carcinomas.
Garinis
George A
GA
Nursing Military Academy, Laboratory of Research, Athens, Greece. g.garinis@erasmusmc.nl
Manolis
Evangelos N
EN
Spanakis
Nick E
NE
Patrinos
George P
GP
Peros
George
G
Menounos
Panayiotis G
PG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D015533:Transcriptional Activation
D015415:Biomarkers; D015820:Cadherins; D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins