Ichiro Yamasaki

Conventional and molecular cytogenetic characterization of a new human cell line, GIST-T1, established from gastrointestinal stromal tumor

Conventional and Molecular Cytogenetic Characterization of a New Human Cell Line, GIST-T1, Established from Gastrointestinal Stromal Tumor

Detection of genetic alterations in advanced prostate cancer by comparative genomic hybridization.

In this study, we examined nine cases of advanced Japanese prostate cancer by comparative genomic hybridization (CGH) to detect chromosomal imbalances across the entire genome and to identify several new regions likely to contain genes important to the development and progression of this disease. These cases had been previously examined for numerical chromosomal aberrations by fluorescence in situ hybridization (FISH). By CGH, the following regions were found to be over-represented (gains), with fluorescence ratio values higher than the threshold: 4p, 6p, 8q, 11q, 12q, 15q, 16p, 17q, 20, and 21 (>4 cases); underrepresentation (losses) involved: 1q, 4q, 5q, 6q, 13q, 14q, and 22 (>4 cases). The shortest regions of overlap (SRO) of gains were noted at 8q24.1 through q24.3, 12q23, and 17q23 through q24 (>5 cases). The SRO of losses were seen at 5q14 through q21, 6q16.1 through q21, 13q21.3 through q22, and 14q21 (>5 cases). Notably, the gain of chromosomes 8 and 12 by CGH was in agreement with the FISH data, suggesting that the gain of chromosomes 8 and 12 may play an important role in prostate carcinogenesis. The genes on the SRO regions were also discussed in relation to oncogenes and bone metastases.

Human mismatch repair gene (hMSH2) product expression in relation to recurrence of transitional cell carcinoma of the urinary bladder

Several convincing studies have shown that the hMSH2 gene plays major roles in mismatch repair by recognizing mismatched bases and preventing mutations during DNA replication. Loss of this function may result in the accumulation of DNA replication errors or even the mutator phenotype (which may be responsible for the multiple mutations required for multistep carcinogenesis), and it has been found to affect the prognosis of patients. Thus, the authors felt that it would be of interest to study the expression patterns of hMSH2 protein in malignant tumors and to assess the correlation of hMSH2 protein to various clinical and pathologic features in these patients.

Photodynamic diagnosis of positive margin during radical prostatectomy: preliminary experience with 5-aminolevulinic acid.

Objectives:  To investigate the feasibility of intraoperative photodynamic diagnosis (PDD) by 5‐aminolevulinic acid (ALA) for the identification of positive surgical margins (PSM) during retropubic radical prostatectomy (RRP) in patients with prostate cancer (PCa).

Vinculin: Its Possible Use as a Marker of Normal Collecting Ducts and Renal Neoplasms with Collecting Duct System Phenotype

Vinculin is a cytoskeletal protein associated with membrane actin-filament-attachment sites of cell-cell and cell-matrix adherens-type junctions. In this article, we examine the expression of vinculin to elucidate its role in human renal neoplasms. We reviewed surgically resected specimens and selected available tissue from 79 renal tumors in 78 patients. There were 55 men and 23 women. Their mean age was 61 years and the mean size of the renal tumors was 6.1 cm. All renal tumors were examined by immunohistochemistry using a monoclonal antibody against vinculin. Overall, 17 (21.5%) renal tumor samples reacted with vinculin. The positive ratio in various types of renal tumors was as follows: conventional-type (clear cell), 0/54; papillary-type, 5/12; chromophobe-type, 5/5; sarcomatoid-type, 3/4; collecting duct carcinoma, 3/3; and oncocytoma, 1/1. The positive rate of conventional-type renal cell carcinomas (RCCs) is significantly different from that of other renal tumors (P < .01). Normal kidney, conventional, and papillary-type RCCs exhibited positive signals in Western blot analysis. These results suggest that vinculin may serve as a useful marker of renal neoplasms with collecting duct system phenotype such as chromophobe-type RCC.

Prostatic signet-ring cell carcinoma: Case report and literature review

Signet‐ring cell carcinoma (SRCC) of the prostate is a very rare neoplasm and there have been only 38 cases reported to date. Here the 39th case of prostatic SRCC containing a small amount of neutral mucin, prostatic specific antigen (PSA) and prostatic specific acid phosphatase (PSAP) in the signet‐ring cells is reported. It was also found that some intracytoplasmic lumina were derived from the shallow or deep invagination of luminal membranes of cancer cells that formed the neoplastic glands. Using immunohistochemistry, a combination of monoclonal antibodies against cytokeratins 7 and 20 as well as PSA and PSAP may be useful in differentiating prostatic primary SRCC from metastatic SRCC originating in the gastrointestinal tract.

Spinal cord hemangioblastomas in von Hippel–Lindau disease

Study Design:Retrospective data analysis.Objective:To clarify the clinical features and surgical management of spinal cord hemangioblastomas in patients with von Hippel–Lindau disease (VHL).Setting:Clinical VHL Research Group in Japan, Japan.Methods:Forty-eight out of 66 patients with associated spinal cord hemangioblastoma among 142 VHL patients were retrospectively examined with respect to clinical features, accompanying lesions and outcome of surgical treatment.Results:Among these 48 patients, 46 of them (95.8%) also had a central nervous system (CNS) hemangioblastoma at another site: 42 (87.5%) with cerebellar hemangioblastoma and 11 (22.9%) with brain stem hemangioblastoma. Twenty-three patients (47.9%) had more than one spinal cord hemangioblastoma. The 48 patients with spinal cord hemangioblastomas collectively had a total of 74 tumors. The tumor was accompanied with a syrinx in 64 and without it in 10 patients. Forty of the 48 patients underwent surgical treatment for their spinal cord hemangioblastomas, and 7 of these 40 underwent surgical treatment twice. When functional changes in the patients after these 47 operations were examined by postoperative evaluation by McCormick’s classification, 39 of these operations (83.0%) resulted in improvement/no change and 8 (17.0%) in aggravation of symptoms.Conclusion:Von Hippel–Lindau disease patients bearing spinal cord hemangioblastomas mostly had a CNS hemangioblastoma at another site. These tumors can be removed in the majority of VHL patients without aggravation. In these patients, when the timing of treatment for spinal cord hemangioblastoma is determined, the probability of occurrence and treatment of other lesions should be considered.

Clinical characteristics of pancreatic neuroendocrine tumors in Japanese patients with von Hippel-Lindau disease.

Objective: The aim of this study was to elucidate the clinical characteristics of pancreatic neuroendocrine tumors (NET) in Japanese patients with von Hippel-Lindau (VHL) disease. Methods: We sent a questionnaire to all members of the Japan Pancreas Society in 2002 asking for the number of patients with VHL and complications of NET and/or cystic lesion in the pancreas. Furthermore, we sent a second questionnaire to obtain detailed information about the clinical characteristics of pancreatic NET. Results: A total of 58 patients with VHL were reported. Among these, 34 (59%) patients had pancreatic lesions, including 10 with pancreatic NET, 23 with a cystic lesion, and one with both. The mean age at identification of pancreatic NET was 34.6 years (range, 22-64 years). The mean diameter of the tumors was 4.3 cm (range, 1-12.5 cm). Distant metastases were found in 2 (20%) cases. During the follow-up period (3.3 years; range, 0-8 years), 7 patients are alive, and 2 patients died of hemangioblastomas. Conclusions: Pancreatic NET in the VHL disease showed a relatively lower incidence of metastasis compared with sporadic non-functioning pancreatic NET, yielding a favorable prognosis. Because they present no hormonal syndrome, periodic screening examinations are warranted to identify pancreatic NET at an early stage.Abbreviations: ACTH = adrenocorticotropic hormone, CNS = central nervous system, NET = neuroendocrine tumor, PP = pancreatic polypeptide, VHL = von Hippel-Lindau

Genome wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population

Through genome-wide association analysis and an independent replication study using a total of 1131 bladder cancer cases and 12 558 non-cancer controls of Japanese populations, we identified a susceptibility locus on chromosome 15q24. SNP rs11543198 was associated with bladder cancer risk with odds ratio (OR) of 1.41 and P-value of 4.03 × 10(-9). Subgroup analysis revealed rs11543198 to have a stronger effect in male smokers with OR of 1.66. SNP rs8041357, which is in complete linkage disequilibrium (r(2) = 1) with rs11543198, was also associated with bladder cancer risk in Europeans (P = 0.045 for an additive and P = 0.025 for a recessive model), despite much lower minor allele frequency in Europeans (3.7%) compared with the Japanese (22.2%). Imputational analysis in this region suggested CYP1A2, which metabolizes tobacco-derived carcinogen, as a causative candidate gene. We also confirmed the association of previously reported loci, namely SLC14A1, APOBEC3A, PSCA and MYC, with bladder cancer. Our finding implies the crucial roles of genetic variations on the chemically associated development of bladder cancer.

Metastatic cardiac tumor from urothelial carcinoma detected by transthoracic echocardiography: a case report

IntroductionCardiac metastasis of urothelial carcinoma is a very rare but clinically important complication. Most cardiac metastases are asymptomatic; symptoms from cardiac metastasis were seen in advanced stage and many of these cases were reported to have a poor prognosis. So it is important to find asymptomatic cardiac metastasis and to start chemotherapy early in order to improve the patient’s prognosis.Case presentationA 73-year-old Asian man was referred to our hospital because of a right ventricular tumor. He had a history of left ureteral cancer 9 years ago. In screening echocardiography for paroxysmal atrial fibrillation, a low echogenic tumor was detected in his right ventricular apex, and characteristic ST segment elevation was detected in electrocardiography. An 18F-fluorodeoxyglucose positron emission tomography revealed abnormal uptake in his right ventricular apex tumor and prostate, and a biopsy of the prostatic tumor showed urothelial carcinoma cells. He received systemic gemcitabine, paclitaxel and cisplatin chemotherapy for the urothelial carcinoma, and the cardiac tumor size was reduced temporarily. Finally, he died of multiple organ failure 16 months after his first admission, but his survival period was relatively longer than previous reports.ConclusionsWe experienced a case of a metastatic cardiac tumor from urothelial carcinoma. We found asymptomatic cardiac metastasis by screening echocardiography and electrocardiography. Our patient received systemic chemotherapy and his survival period was relatively longer than previous reports. Electrocardiography and echocardiography may be useful to find asymptomatic cardiac metastasis of neoplasms.