These results indicate an important role of CD44 methylation in the progression and metastasis of prostate cancer, although the amount of methylational heterogeneity is substantial among metastatic sites within the same patient.

Expression of the KAI1 gene, a metastasis-suppressor for prostate cancer, is reduced in all foci of prostatic metastasis. The altered regulatory mechanism is not strongly related to mutations or allelic losses of the KAI1 gene in prostate tumors. Since transcriptional silencing of genes has been found to be caused by epigenetic mechanisms, we have investigated the involvement of this epigenetic regulation of KAI1 expression in prostate cancers. The methylation status of the KAI1 promoter region was examined by restriction-enzyme digestion and sequencing, after amplifying a 331-bp fragment in the GC-rich promoter region from 4 human prostate cancer cell lines treated with bisulfite. The same 4 cell lines were also exposed to various concentrations of the demethylating agent, 5-aza-2′ ′ ′ ′-deoxycytidine

The syndrome of inappropriate secretion of antidiuretic hormone (ADH) was recognized in a 68-year-old man with a poorly differentiated metastatic adenocarcinoma of the prostate. Elevated levels of ADH were found in the tissues of the primary tumor and lymph node metastasis. The patient's clinical course is detailed and the pathophysiology of this syndrome is discussed. To our knowledge, this case is the ninth reported case of syndrome of inappropriate secretion of ADH with adenocarcinoma of the prostate. Antidiuretic hormone activity was proven in only three cases including this case.

Key words: renal cell carcinoma; gelatinase activity; matrix metalloproteinases; film in situ zymography; gelatin zymography; RT-PCR; Western blottingIn Japan, renal cell carcinoma is the 13th most common solid malignancy and the 16th leading cause of cancer mortality, with more than 5,000 new cases and 3,000 deaths having been documented in the year 2001. Renal cell carcinoma is a highly vascular neoplasm with an unpredictable pattern of recurrence, and the pathological stage is one of the predictors for metastasis. 1,2 Other pathological factors associated with metastasis include high tumor grade, 3,4 nuclear size, 5 and tumor proliferation indices. 6 -8 Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of degrading the basement membrane and extracellular matrix (ECM). MMPs are secreted as inactive pro forms and are transformed into activated forms after cleavage of a pro-peptide domain of the molecule. 9 -14 Gelatinolytic degradation of the ECM is a fundamental event in the regulation of tumor proliferation and metastasis. 9 -12 There have been several reports recently regarding the prognostic significance of increased MMP expression in cancers in several human organs such as the esophagus, 15,16 stomach, 17,18 colon, 19,20 breast, 21,22 pancreas, 23 prostate, 24,25 lung, 26,27 ovary 28,29 and kidney. 30-33 The expression level of the ECM degrading MMP-2 and MMP-9 has been shown to correlate with the metastatic potential of renal cell tumors (RCTs). 30 -33 The newly developed film in situ zymography (FIZ), 34 -38 which uses a gelatin film over unfixed frozen tissues, can show in situ gelatinolytic activity on tissue sections. Using the FIZ method, we determined the in situ localization of gelatinolytic activities in cancerous and normal kidney tissues. We also attempted to clarify the major MMP involved in gelatinolytic activity in RCTs. We investigated the correlation of MMP expression detected by GZG with the intensity of in situ gelatinolytic activity, as well as the possible relationship of FIZ findings to several clinico-pathological factors in RCT patients.

Prostate-specific antigen screening has significantly increased the percentage of men who are diagnosed with low-risk prostate cancer. All men undergoing retropubic radical prostatectomy for primary treatment of prostate cancer from April 2004 to September 2010 in our hospital were examined in order to determine whether active surveillance criteria could be applied to Japanese men. From pathological data of prostate biopsies, whether these men met five published criteria for active surveillance (Johns Hopkins Medical Institution, Prostate Cancer Research International: Active Surveillance Study, University of California, San Francisco, Toronto and Kakehi criteria) was evaluated. Men who met any of the criteria had a statistically significant lower extracapsular extension rate and organ-confinement rate. From the view of the possibility of Gleason upgrading and organ-confinement rate, the Johns Hopkins Medical Institution and Prostate Cancer Research International: Active Surveillance Study criteria showed to be appropriate for Japanese patients. However, the present study had limitations of selection bias and a limited number of cases.