Expression of nm23-H1 in uveal melanoma.
Uveal melanoma (UM) is the most common malignant intraocular tumor in adults. Despite the high accuracy of clinical diagnosis and advances in local treatment, more than 50% of UM patients develop metastasis within 10 years of initial diagnosis. NM23 is one of the human metastasis suppressor genes. Reduced nm23-H1 expression is correlated with high metastatic potential in many different cancers. The purpose of this study is to investigate the expression of nm23-H1 in UM and its potential value as a prognostic marker. Immunostaining of nm23-H1 was verified in five human UM cell lines with different metastatic potentials. The expression level of nm23-H1 mRNA was evaluated with one-step quantitative real-time PCR. The invasion ability of the cell lines was assessed before and after silencing nm23-H1 with small interference RNA. Thirty-two cases of paraffin-embedded specimens of human UM were immunostained with nm23-H1 monoclonal antibody. The immunostaining was evaluated in a semiquantitative fashion based on extent and intensity. The real-time PCR results of five human UM cell lines showed that expression of nm23-H1 was higher in cell lines with low metastatic potential compared with those with high metastatic potential (P<0.05). The invasive ability of the UM cell lines increased after silencing nm23-H1 expression with small interference RNA (P<0.05). The immunostaining of nm23-H1 was cytoplasmic in all cell lines and UM patients samples. The increased immunostaining intensity of nm23-H1 in patients' samples was associated with better survival rate (Kaplan-Meier test P=0.0097). The expression of nm23-H1 was not correlated with other prognostic factors. It can be concluded that nm23-H1 may be a prognostic marker to predict the survival rate of UM patients and it has the potential to identify high-risk patients.
Bakalian
Silvin
S
McGill University/Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, Quebec, Canada. sbakalian@hotmail.com
Marshall
Jean Claude
JC
Faingold
Dana
D
Logan
Patrick
P
Antecka
Emilia
E
Burnier
Miguel N
MN
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007797:Laminin / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054778:NM23 Nucleoside Diphosphate Kinases / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D004338:Drug Combinations; D007797:Laminin; D054778:NM23 Nucleoside Diphosphate Kinases; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C059485:matrigel; D003094:Collagen; C517938:NME1 protein, human