Expression of nm23-H1 gene product in sarcomatous cancer cells of renal cell carcinoma: correlation with tumor stage and expression of matrix metalloproteinase-2, matrix metalloproteinase-9, sialyl Lewis X, and c-erbB-2.
OBJECTIVE
To investigate the clinical significance of nm23-H1 gene product in sarcomatous cancer cells, because this is known as a tumor-metastasis suppressor. Renal cell carcinoma with sarcomatoid cancer cells is characterized by high malignant potential and a poor prognosis.


METHODS
We investigated the expression of nm23-H1 gene product in the carcinomatous and sarcomatous component (CC and SC) of renal cell carcinoma using immunohistochemical techniques and the relationships between the expression and clinicopathologic features. We also examined the expression of matrix metalloproteinase (MMP)-2, MMP-9, sialyl Lewis X, and c-erbB-2 in the SC because these proteins are regulated by the nm23-H1 gene or its products.


RESULTS
We examined 20 renal cell carcinoma specimens that contained an SC and CC. The CC of 12 of the 20 tumors stained positively for nm23-H1 gene product. In contrast, the SC of only 3 of the 20 stained positive. The reduced expression of nm23-H1 gene product in the SC correlated significantly with tumor invasion (P <0.01), but not with tumor size or metastasis. In contrast, the expression of the nm23-H1 gene product in the CC was not associated with these pathologic features. Expression of the nm23-H1 gene product correlated negatively with MMP-2 expression (r = -0.48, P = 0.03). Other factors did not show such significant correlations with nm23-H1 gene product expression.


CONCLUSIONS
Our results suggest that low expression of nm23-H1 gene products may play important roles in tumor invasion, and that this process is mediated in part by overexpression of MMP-2.
Ohba
Kojiro
K
Department of Urology, Nagasaki University School of Medicine, Nagasaki, Japan.
Miyata
Yasuyoshi
Y
Koga
Shigehiko
S
Kanda
Shigeru
S
Kanetake
Hiroshi
H
D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016256:Lewis X Antigen / Q000032:analysis*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D009844:Oligosaccharides / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000080506:Sialyl Lewis X Antigen
D000951:Antigens, Neoplasm; D016256:Lewis X Antigen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D009844:Oligosaccharides; D018719:Erb-b2 Receptor Tyrosine Kinases; D000080506:Sialyl Lewis X Antigen; C517938:NME1 protein, human