Yuichi Tsujimoto

Elevated Expression of Valosin-Containing Protein (p97) Is Associated with Poor Prognosis of Prostate Cancer

Purpose: Valosin-containing protein (VCP) has been shown to be associated with metastasis and prognosis in human cancers. In the present study, the correlation of VCP with recurrence and prognosis in patients with prostate cancer (PCA) receiving conservative therapy was examined. Experimental Design: VCP expression was analyzed immunohistochemically in 136 patients ranging from 46 to 92 years (median, 72 years), who received conservative therapy, including androgen deprivation, radiotherapy, or watchful waiting. Staining intensity of tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 10 patients. Results: Thirty-two cases (23.5%) showed level 1 and 100 (76.5%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCPmRNA expression in level 2 (n = 5) than level 1 cases (n = 5; P < 0.05). A significant difference was observed between VCP level 1 and 2 patients in the positive rate for the digital rectal examination (P < 0.01), serum prostate-specific antigen level (P < 0.0001), cancer volume (P < 0.0001), Gleason score (P < 0.0001), stage (P < 0.0001), and progression-free and overall survival (P < 0.0001 for both). Multivariate analysis revealed VCP expression level, serum prostate-specific antigen level, and Gleason score to be independent prognosticators for progression-free and overall survival. Progression of PCA was found in 9.4% of level 1 but in 64% of level 2 patients. Conclusions: PCA with level 1 VCP expression could be treated conservatively.

Frequent Fas gene mutations in testicular germ cell tumors.

The Fas (Apo-1/CD95)/Fas ligand (L) system is involved in cell death signaling, and has been suggested to be important for the regulation of germ cell apoptosis in the testis. Mutations of the Fas gene may result in accumulation of germ cells and thus might contribute to testicular carcinogenesis. The open reading frame of Fas cDNA was examined in 24 cases of testicular germ cell tumors (TGCTs), comprised of 19 pure histological type (15 seminomas, 3 embryonal carcinomas, 1 immature teratoma) and 5 mixed-type tumors. Mutations of the Fas gene were found in nine (37.5%) of these cases. Each lesion with a homogeneous histological picture was selectively microdissected using a laser capture microdissection method: samples consisted of 18 lesions from seminomas, 7 embryonal carcinomas, 4 immature teratomas, 2 choriocarcinomas, and 1 from a yolk sac tumor. Microdissected genomic DNA was examined to determine which mutations were derived from which kind of histological lesion. Eleven mutations were detected in 10 TGCT lesions from nine cases, but none were found in benign lesions. All were point mutations, and eight missense mutations occurred in exon 9 encoding the core protein of the death domain essential for apoptotic signal transduction. Three were silent mutations. Mutations were found in the seminoma (27.8%) and embryonal carcinoma lesions (62.5%), but none were found in the one yolk sac tumor, two choriocarcinomas, or four immature teratoma lesions. Each seminoma and embryonal carcinoma lesion found in the same case had a different type of Fas mutation from the others. Mouse T-cell lymphoma cells transfected with missense mutated genes were resistant to apoptosis induced by anti-Fas antibody, indicating these to be loss-of-function mutations. These findings suggested a role of Fas gene mutations in the pathogenesis of TGCTs.

Utility of immunohistochemical detection of prostate‐specific Ets for the diagnosis of benign and malignant prostatic epithelial lesions

Background : Human prostate‐specific Ets (hPSE) belongs to the Ets family. It regulates the proliferation, differentiation, and development of prostate epithelial cells. A recent study showed that hPSE can be detected in normal glands but not in cell lines established from prostate cancer (PCA), suggesting a translational disorder of hPSE from mRNA to protein in PCA. Immunohistochemical detection of hPSE could therefore be another method of differential diagnosis of PCA from other proliferative conditions in the prostate.

Survey of Overactive Bladder Symptoms Influencing Bother Before and After Treatment With Tamsulosin Hydrochloride in Japanese Patients With Benign Prostatic Hyperplasia

OBJECTIVE To evaluate the relation between bother and overactive bladder (OAB) symptoms in patients with benign prostatic hyperplasia (BPH) patients using questionnaires: the BPH Impact Index (BII) and the OAB symptom score (OABSS). Annoyance from BPH usually provides the basis for a patients decision to seek medical treatment. However, a study investigating the bother caused by OAB symptoms in patients with BPH and OAB has not been fully conducted. METHODS The present study included 100 male patients who were diagnosed with BPH and OAB according to questionnaire criteria. All patients were instructed to take tamsulosin for 28 days. The relation between the BII and OABSS was assessed to determine the factors influencing OAB symptoms on the BII before and after treatment. RESULTS The BII correlated positively with the OABSS, and multivariate analysis showed that the subscore of urgency was the only independent factor influencing the BII. Even after treatment, lower urinary tract symptoms were diagnosed as OAB using the OABSS criteria in 45 (45.0%) of the 100 patients. In these patients, the BII still correlated positively with the OABSS. However, multivariate analysis showed that the subscore of urgency incontinence, not urgency, was the only independent factor influencing the BII, although the subscore of urgency incontinence was significantly decreased with tamsulosin treatment. CONCLUSION The degree of bother correlated with the degree of OAB symptoms in patients with BPH and OAB at baseline and after treatment with tamsulosin. The OAB symptom causing the bother was altered by treatment with tamsulosin in these patients.

Rare case of the hyaline vascular type of Castleman's disease of the kidney

Abstract:  Castlemans disease (CD) is a rare disorder characterized by a benign proliferation of lymphoid tissue. Most cases tend to present as a mediastinal mass. A few extrathoracic cases involving nodal and extranodal locations have previously been reported. To the best of our knowledge, however, only one case of CD of the kidney has been published in an English report. We herein report a rare case of CD presenting as a left renal tumor. A 70‐year‐old male was examined by computed tomography for a follow‐up for colonic diverticulitis and a left renal mass measuring 2.0 cm in diameter was incidentally found. The patient underwent a left partial nephrectomy for a left renal mass and a histopathological analysis demonstrated the hyaline vascular type of CD. Based on our findings, CD should be included in the differential diagnosis of renal tumors.

Analysis of Fas gene mutations on laser capture microdissected specimens from renal cell carcinoma.

Renal cell carcinoma (RCC) expresses Fas antigen on the cell surface, and thus could be sensitive to apoptosis induced by the binding of Fas ligand. Fas gene mutations might be involved in the development of RCC. Fas gene mutations were examined in genomic DNA extracted from RCC lesions. With use of laser capture methods, one RCC and one non‐neoplastic lesion per case were microdissected from 15 patients with RCC. Polymerase chain reaction‐amplified products were directly sequenced. Loss of heterozygosity (LOH) was examined at four sites of known polymorphism. Mutations of the Fas gene were detected in 3 RCC lesions from 3 (20%) of 15 cases. All mutations were point mutations, 2 missense and one silent, in exons 7 and 9. Non‐neoplastic tissues never showed Fas gene mutations. Nine of 15 cases (60.0%) were heterozygous for one or more sites of the known biallelic polymorphisms, i.e., at nucleotides ‐1377, ‐670, 416, and 836. Two of these 9 cases showed LOH at promoter region ‐670. Mouse T‐cell lymphoma cells transfected with missense mutated genes were resistant to apoptosis induced by anti‐Fas antibody, indicating these to be loss‐of‐function mutations. The results of the present study suggest that Fas gene mutations play a role in the pathogenesis of RCC.

Rare case of aggressive angiomyxoma presenting as a retrovesical tumor

Abstract  Aggressive angiomyxoma (AAM) is a rare mesenchymal benign tumor that preferentially involves the pelvic and perineal regions in relatively young females. We report here a rare case of AAM presenting as a retrovesical tumor in a male patient. A 59‐year‐old man undergoing abdominal ultrasound examination because of benign prostatic hyperplasia was found to have a retrovesical mass. Computed tomography and magnetic resonance imaging of the pelvis showed the retrovesical tumor to be 7.4 × 6.7 cm. The tumor was resected, and diagnosed histopathologically as AAM. The patient showed no recurrence 26 months after resection. Although the majority of retrovesical tumors are considered to be sarcoma or neurogenic tumor, AAM should also be recognized as a differential diagnosis.

Changes in extent and zonal distribution of prostatic adenocarcinoma in patients preoperatively treated with neoadjuvant endocrine therapy: Analysis on whole‐mounted prostatectomy specimens

Abstract Background: An increasing number of pharmacologic agents that induce reversible androgen deprivation are available for neoadjuvant endocrine therapy (NET) for prostatic adenocarcinoma (PCA). If information about the regression pattern of PCA after NET is recognized, more effective decision‐making for subsequent therapies such as prostatectomy and radiotherapy, will be possible.