Overexpression of the nm23H1 gene has been associated with the suppression of metastasis in several solid tumors. However, in colorectal carcinoma and neuroblastoma, increased levels of nm23 H1 nucleoside diphosphate kinase A (NDPKA) mRNA are associated with tumorigenesis. To determine the role of rim23 H1/ NDPKA in the prostate, normal and/or malignant tissue samples from 29 consecutive patients were studied. Levels of rim23 H1/NDPKA mRNA and nm23 H1/NDPKA mRNA protein were determined in tissue from 18 and 27 patients, respectively. In all, 16 of the 18 tumor samples expressed increased levels of nm23 H1/NDPKA mRNA as compared with those measured in normal tissue. The level of rim23 H1/NDPKA mRNA was > 10-fold higher in a metastatic lymph node than in normal prostate tissue. All cancer specimens and areas of prostatic intraepithelial neoplasia showed immunoreactivity with the nm23 H1/ NDPKA antibody; however, normal prostatic tissue was unreactive. These findings suggest that overexpression of the rim23 H1/NDPKA gene occurs frequently in adenocarcinomas of the prostate and may be an early event in prostate cancer tumorigenesis.Over the last 15 years, adenocarcinoma of the prostate has become the most common cancer of men in the United States, with the estimated incidence being 23% [2]. Prostate cancer accounts for more than 12% of cancer deaths among men, and the mortality associated with this malignancy in men is second only to that of lung cancer. This high death rate occurs despite the observation that prostate cancer is being identified at an earlier clinical stage through aggressive screening studies [3]. Therefore, biological events rather than clinical stage alone are important in the formation of metastases.Correspondence to: D. P. Wood, Jr.; Fax: +1 (606) Tumorigenicity and metastatic potential are related to a series of complex independent and linked sequential events [5]. The formation of metastases required cellular transformation, invasion through the basement membrane, cell motility, penetration of the vascular and/or lymphatic beds, angiogenesis, and proliferation at distant sites [6,15]. Altering the ability of a cell to perform any of these activities would suppress the metastatic potential of that cell. Steeg et al. [20], in an attempt to identify the genes involved in suppressing or promoting metastasis, performed differential colony hybridization of mRNA between melanoma cell lines with low and high metastatic potentials. These experiments resulted in the discovery of a potential metastatic suppressor gene, rim23 H1, with low levels of nm23 H1 mRNA expression being found in highly metastatic melanoma cell lines and higher levels occurring in cell lines with low metastatic potential [20]. Additional experiments determined that rim23 H1 is part of a gene family, and two nm23 genes have been identified: rim23 H1 and nm23 H2. The gene product of nm23 H1 is nucleoside diphosphate kinase A (NDPKA) [7], whereas that of nm23 H2 is nucleoside diphosphate kinase B [7,19].Various human tumor tissues ha...

Cytologic evaluation of body cavity fluids is useful to detect malignancy within the pleural and peritoneal spaces. A definitive diagnosis cannot always be made on cytologic evaluation alone. As malignant processes may show abnormal DNA content, DNA analysis of effusions may be useful. Therefore, we determined the DNA content of 37 effusions by flow cytometry (FC) and image analysis (IA) using the CAS 200. Of the 37 fluids evaluated, 18 were cytologically malignant, 15 benign, and four atypical. Overall, 22 fluids (60%) showed concordance between FC and IA. None of the benign fluids were aneuploid. All showed diploid histograms or diploidy with increased proliferating cells. Three of four atypical fluids had increased proliferating cells by either FC or IA, whereas one was diploid by both methods. Aneuploidy was detected in 13 malignant fluids: five were aneuploid by both methods and eight by only one method. IA identified aneuploidy in five of those eight cases, while three were identified by FC. Three of the cytologically malignant fluids were diploid by both methods, and two showed increased proliferating cells by IA and diploidy by FC. The specificity of both methods was 100%. However, the sensitivity of identifying a malignant fluid by aneuploidy is low, 44% for FC and 55% for IA. IA appears to identify small aneuploid populations more frequently than FC. The detection of aneuploidy in effusions is highly suggestive of malignancy, and the combination of both techniques gives the highest detection rate (72%). However, neither are as sensitive as traditional cytologic evaluation with the occasional use of additional histochemical stains.

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