The Biological Effect of Hepsin on the Proliferation and Invasion of PC-3 Prostate Cancer Cells

OBJECTIVE Recent studies have shown that hepsin, a type of transmembrane serine protease, is highly upregulated in prostate cancer, but, little is known about its role in progression and invasion of this cancer. We constructed a hepsin-expressing plasmid and transfected it into PC-3 cells to investigate the effect of the hepsin gene on the biological behavior of the PC-3 cells. METHODS Plasmid pHepsin-IRES2 was transfected into prostate cancer PC-3 cells using Fugene6, and the cells with stable hepsin expression were screened and selected with Zeocin (600 mg/L). The hepsin mRNA level was measured by real-time PCR and the growth curve of the PC-3-transfected cells assessed using MTT and BrdU assays. A Boyden chamber was used to examine the difference in invasion and metastases between transfected and non-transfected cells. RESULTS The hepsin mRNA level in pHepsin-IRES2 transfected -PC-3 cells was significantly higher than that found in the control PC -3 cells. While the growth curve of the hepsin gene transfected PC -3 cells showed that there was no significant effect on proliferation, the invasive ability of the pHepsin-IRES2 transfected PC-3 cells, as compared with control cells, was significantly increased (P<0.05). CONCLUSION The results suggest that even though hepsin has no effect on the proliferation of prostate cancer PC-3 cells, it does promote cellular invasion and metastasis.Therefore hepsin may have a role in the development of prostate cancer.     

Mucin-Producing Urothelial-Type Adenocarcinoma of the Prostate （a Case Report and Review of the Literature）

OBJECTIVE To report clinical and pathologic findings of one case of mucin-producing urothelial-type adenocarcinoma of the prostate, and to discuss the diagnosis and prognosis of this disease. METHODS The patient was a 60-year-old man who had an 8-month history of urinary frequency and dysuria culminating in an aggravating condition for 10-days. Laboratory results were tPSA 3.0 and fPSA 0.4. An ultrasound and digital rectal exam showed no abnormal findings, so he was diagnosed as having benign prostatic hyperplasia, and underwent a transurethral prostate resection. RESULTS The findings during the operation resembled benign prostatic hyperplasia (BPH), whereas the pathological exam showed that the pro-static construction was deranged in the tumor infiltrating region, with many mucin lakes and signet ring cell in the cancer tissue. Immunohisto-chemical staining revealed that the cancer tissue was negative for prostate-specific antigen (PSA) and postive for carcinoembryonic antigen (CEA). Final diagnosis: mucin-producing urothelial-type adenocarcinoma of the prostate. After 50 Gy radiotherapy, the patient was free of recurrent signs and metastasis up to 8 months after operation. CONCLUSION Mucin-producing urothelial-type adenocarcinoma of the prostate is extremely rare. Its differential diagnosis mainly includes conventional prostatic adenocarcinoma with mucin production and secondary adenocarcinoma. The diagnosis and treatment of this disease should be further investigated.     

卵巢移行细胞癌:一例报道与文献复习(英文)

Transitional cell carcinoma(TCC)of the ovary is a rare and recently recognized subtype of ovarian epithelial cancer.We presented the first case report from our Institute(Sheri Kashmir Instiute of Medical Sciences,Srinagar,India),which was initially misdiagnosed as stromal cell carcinoma(granulosa cell tumour),and on review of histopathology with immunohistochemistry,the diagnosis of TCC of the ovary was established.The aim of this article was to describe the typical case of primary TCC of the ovary and to review the literature for information on TCC management.     

Glucocorticoids suppress tumor angiogenesis and growth of prostate cancer

Hormone-refractory prostate cancer ( HRPC) sometimes is responsive to treatment with glucocorticoids, such as prednisolone, hydrocortisone and dexamethasone, but the underlying mechanisms are not well established. In a recent paper (Clin Cancer Res, 2006, 12:3003-3009), Yano et al. Hypothesized and confirmed that the therapeutic effect of glucocorticoids on HRPC is attributed to inhibition of angiogenesis. A prostate cancer cell line DU145 that expresses glucocorticoid receptor was used to study the effect of dexamethasone (Dex) on the expres-     

Expression of Thrombospondin-1 is Correlated with Microvessel Density in Prostate Cancer

OBJECTIVE To observe the expression of thrombospondin-1 ( TSP-1) in prostate cancer, and examine its expression in relation to angiogenesis. METHODS The expression of TSP-1 and microvessel density (MVD) were studied in 22 prostate cancer patients by using immunohistochemistry. RESULTS Positive expression of the TSP-1 protein was detected in 16 (72.7%)of the 22 cases. Most of the positive staining for TSP-1 was seen in the cytoplasm of the cancer cells, but some was in the extracellular matrix. The mean MVD in the 22 prostate cancer cases was 71.21±31.14 vessels per 100 high field of vision. Tumors with an elevated expression of TSP-1 showed a high MVD resulting in a correlation between TSP-1 immunopositivity and microvessel density that was highly significant (r= 0.54, P=0.009). CONCLUSION TSP-1 is strongly expressed in most prostate cancers and is associated with neovascularization. Therefore TSP-1 is a likely contributor to the extensive neovascularization in prostate cancer and increased TSP-1 expression might participate in an angiogenic phenotype.     

膀胱颈部颗粒细胞瘤一例报告(英文)

We reported a case of a GCT of the urinary bladder and review the literature.A 23-year-old female presented with dysuria that had lasted for the previous 6 months.MRI revealed a 3×2.5 cm global mass in the anterior wall of urinary bladder.Cystoscopy showed a semispherical tumor approximately 3 cm in diameter that was covered with normal bladder mucosa and extended from the bladder neck to the anterior wall of the bladder.The patient underwent transurethral resection of the tumor.Histological examination and...     

The Relationship of PSA, PSAD and Clinicopathological Stage in Patients with Prostate Cancer

OBJECTIVE To investigate the relationship between the clinicopatho- logical stage and serum prostate specific antigen(PSA)concentration and PSAdensity(PSAD)in patients with prostate cancer. METHODS The clinicopathological stage was determined on the basis of a pathological examination and clinical data in 65 prostate cancer patients treated by radical prostatectomy.PSA and PSAD were measured before the operation.The Spearman rank correlation was applied to evaluate the relationship between the clinicopathological stage,serum PSAconcentration and PSAD. RESULTS Patients with higher PSA and PSAD were significantly more likely to have higher clinical stages,a higher Gleason score,positive surgical margins,capsular penetration,and seminal vesicle invasion(each P<0.05). But there was no significant association between PSA and lymph node metastasis(P=0.053).The levels of serum PSA concentration and PSAD were significantly correlated with the clinical stage(P<0.05)in the prostate cancer patients. CONCLUSION The level of both PSA and PSAD were significantly correlated with the clinical stage(P<0.05)in the prostate cancer patients.But PSAD may be a more powerful predictor of clinical stage and prognosis than PSA.     

Progress in Diagnosis and Treatment of Small Cell Carcinoma of the Cervix

Small cell carcinoma of the cervix(SCCC)belongs to the neuroendocrine carcinomas,and it is a rare gynecological tumor of high-potential malignancy.It has a poorer prognosis compared to cervical squamous cancer or adenocarcinoma,and the therapeutic regimen of the disease differs.Diagnosis is based on pathomorphological characteristics,i.e.,the small and round cancer cel s(oat cel)which are uniform in shape and size,with the immunohistochemical marker helpful for diagnosis.Combined therapy is first recommended.Postoperative chemotherapy with platinum/etoposide (PE),vincristine/adriamycin/cyclophosphamide(VAC)and taxel/carboplatin (TP)can markedly improve the prognosis of early SCCC patients.     

Mixed Medullary-follicular Thyroid Carcinoma： Report of a Case and Review of the Literarture

Mixed medullary-follicular carcinomas （MMFCs） are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. These tumors are rare and less than 40 cases have been described in the literature since the early 1980s The term medullary-follicular thyroid carcinoma denotes a tumor which exhibits the features of a medullary carcinoma and shows positive expression of calcitonin on immunohistochemistry. It is a follicular-derived thyroid carcinoma and is positive for thyroglobulin expression within the same tumor. Most reported cases have lymph node involvement at the time of diagnosis. In cases having disease progression, distant metastases develop in the lung, liver, mediastinum and bone. We report a case of a male patient with mixed medullary-follicular thyroid carcinoma and a review of the literature.     

Clinical significance of p53, MDM2 and bcl-2 expression in transitional cell carcinoma of the bladder

We investigated the prognostic and predictive relevance of p53, MDM2, and bcl-2 protein expression in patients with transitional cell carcinoma (TCC) of the bladder. The expression of p53, MDM2 and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded specimens from 119 patients whose clinicopathologic data confirmed TCC of the bladder. Multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters were examined. Sixty-one, 12, and 17% of cases were considered positive for expression of p53, MDM2 and bcl-2, respectively. p53 expression correlated with stage (p=0.0209), but not MDM2 and bcl-2 with any clinicopathologic parameters. In Cox's regression analysis, staging demonstrated a statistically worse prognosis (hazard ratio 1.636; p=0.0059) while bcl-2 (hazard ratio 0.179; p=0.0474) expression showed favorable prognosis in stage T2-4 invasive TCC of the bladder. Co-expression with p53/MDM2 (hazard ratio 0.367; p=0.0401) and p53/bcl-2 (hazard ratio 3.487; p=0.0111) overexpression were associated with favorable and unfavorable prognosis in stage T2-4 invasive TCC of the bladder, respectively. Our results indicate that staging is the most useful parameter to predict clinical outcome in patients with TCC of the bladder. Determinations of bcl-2 and co-expression p53/MDM2 and p53/bcl-2 may be useful for predicting tumor behavior and prognosis in stage T2-4 invasive type TCC of the bladder.     

Pathology of the prostate in radical cystectomy specimens: a critical review

Our aim was to critically review clinico-pathological features of incidental prostate tumors in cystoprostatectomy specimens and to evaluate implications for patients' management. Data were identified by a structured MEDLINE search. Studies addressing incidence, pathological characteristics, and/or clinical significance of prostate tumors or related pre-malignant lesions from cystoprostatectomy series were reviewed in detail. The reported incidence of prostate adenocarcinoma in cystectomy specimens is highly variable and mostly depending on the histopathology technique of sampling. The clinical significance of these incidentally discovered cancers remains questionable, as the outcome of patients depends on the prognosis of the bladder tumor. For those candidates for prostate sparing surgery, it seems reasonable to include a routine prostate biopsy in the standard preoperative work-up as relevant PSA values to exclude cancer are lacking. Reports of prostatic urethral involvement at the time of radical cystectomy are mostly retrospective. Thus, it is likely that the true incidence of involvement with urothelial carcinoma is underreported. It has been suggested that multifocal bladder tumors, CIS in the bladder and bladder tumor location in the bladder neck are independent risk factors for prostatic urothelial carcinoma. Prostatic stromal involvement, which reflects the depth of invasion, is the most important prognostic factor. Poorly differentiated prostate adenocarcinoma and urothelial carcinoma often share overlapping morphologic features and it can be sometimes difficult to differentiate between these two entities.     

Clusterin as a Diagnostic and Prognostic Marker for Transitional Cell Carcinoma of the Bladder

We investigated the feasibility of profiling and measuring the concentration of clusterin in urine and serum for individuals with transitional cell carcinoma (TCC) of the bladder and comparing it with nontumor controls. In addition, we analyzed the correlation of expression of clusterin in specimens of TCC to various clinicopathologic parameters and prognosis of bladder cancer. Blood and urine samples were used from 68 patients with TCC of the bladder and from 61 patients with benign urological diseases. Enzyme-linked immunosorbent assays (ELISA) were performed for clusterin from serum and urine. Quantitation of clusterin mRNA was carried out in 68 bladder tumor specimens from radical cystectomy or transurethral resection and 26 normal bladder specimens from BPH patients by using RT-PCR method. Correlation for the expression of clusterin mRNA with clinicopathologic parameters was analyzed. Serum and urine clusterin was significantly higher in individuals with bladder cancer than control (p = 0.001). Sensitivity and specificity of serum and urine clusterin as a tumor marker for TCC of the bladder was found to be 80%, 91%, 87.1% and 96.7% respectively. Clusterin expression was significantly higher in TCC specimens than normal tissue specimens (P < 0.001). Expression of clusterin was significantly higher in patients with invasive TCC of the bladder than that in patients with superficial TCC and control (P < 0.001). Overexpression of clusterin mRNA was significantly associated with tumor recurrence and overall survival (p < 0.001). The recurrence-free survival time of patients with overexpression of clusterin was significantly shorter than that of patients with weak expression of clusterin (9.8 months vs. 35.2 months). Clusterin may be considered as a potential diagnostic and prognostic biomarker for bladder cancer using urine, serum and/or molecular biology techniques.     

膀胱移行细胞癌组织中cyclinD1和CDK4的表达及其与临床病理的关系

目的　研究膀胱移行细胞癌组织中cyclinD1和CDK 4的表达及其与临床病理变化的关系。方法　采用免疫组化方法对 8例正常膀胱和 69例膀胱移行细胞癌组织中cyclinD1和CDK 4的表达进行观察。 结果　膀胱移行细胞癌组织中cyclinD1的表达高于正常膀胱组织 (P <0 .0 5 )。cyclinD1表达阳性者的肿瘤细胞分化较差 ,术后易复发 ,生存时间较短 ;而CDK 4的阳性表达仅与患者术后复发有关 (P <0 .0 5 ) ,与病理分级和生存时间无关 (P >0 .0 5 )。结论　cyclinD1的表达可作为判断膀胱细胞癌病理分级 ,术后复发和临床预后的指标 ,而CDK 4只能作为术后复发的参考指标。     

Prostatic involvement in bladder cancer. Prostate mapping in 20 cystoprostatectomy specimens

Twenty prostate glands from patients with either high-grade papillary tumors (19 patients, 15 of whom also had peripheral carcinoma in situ) or multifocal carcinoma in situ (1 patient) of the bladder who underwent cystoprostatectomy were studied histologically by mapping. Prostatic duct involvement by urothelial carcinoma was noted in nine patients, two with extensive involvement and seven with focal involvement confined to periurethral ducts. Carcinoma in situ of the bladder was observed in each of the nine patients and intraepithelial permeation appeared to be the predominant manner of spread of cancer cells into the prostate. The prostatic involvement was clinically silent and it may be a potential source of failure of conservative modalities of treatment of high-grade bladder cancer. A routine diagnostic transurethral prostatic biopsy may be recommended in the workup of patients with carcinoma in situ and high-grade carcinomas of the bladder. An incidental observation was the presence of 14 occult prostatic adenocarcinomas.     

Urothelium-specific expression of an oncogene in transgenic mice induced the formation of carcinoma in situ and invasive transitional cell carcinoma.

Although many genetic alterations are known to be associated with human transitional cell carcinoma (TCC) of the urinary bladder, relatively little is known about the roles of these molecular defects, singular or in combination, in bladder tumorigenesis. We have developed a transgenic mouse model of bladder tumorigenesis using a 3.6-kb promoter of uroplakin II gene to drive the urotheliums-specific expression of oncogenes. In this study, we demonstrate that transgenic mice bearing a low copy number of SV40T transgene developed bladder carcinoma in situ (CIS), whereas those bearing high copies developed CIS as well as invasive and metastatic TCCs. These results indicate that the SV40T inactivation of p53 and retinoblastoma gene products, defects frequently found in human bladder CIS and invasive TCCs, can cause the aggressive form of TCC. Our results also provide experimental proof that CIS is a precursor of invasive TCCs, thus supporting the concept of two distinct pathways of bladder tumorigenesis (papillary versus CIS/invasive TCC). This transgenic system can be used for the systematic dissection of the roles of individual or combinations of specific molecular events in bladder tumorigenesis.     

Assessment of microsatellite instability in urine in the detection of transitional-cell carcinoma of the bladder

Loss of heterozygosity (LOH) and alterations in microsatellite DNA markers have been reported in bladder-cancer tumors. We have studied, in a blinded fashion, using PCR-based microsatellite analysis, genetic alterations of cells exfoliated in urine of 59 Caucasian patients and control patients; 31 with initially confirmed bladder transitional-cell carcinoma (TCC), 17 with signs and symptoms suggestive of bladder cancer, 6 control patients who underwent renal transplantation, and 5 control patients with urolithiasis. Microsatellite analysis of cells exfoliated in the urine allowed the diagnosis of 83% (10/12) of patients with bladder TCC recurrence confirmed by cystoscopy, while 100% of patients followed up for transitional-cell carcinoma of the bladder for up to 12 months without evidence of tumor recurrence upon routine cystoscopy showed no microsatellite alterations. None of the patients without neoplasia (negative controls) had any microsatellite alterations, whereas all patients who underwent renal transplantation had additional new alleles corresponding to contamination with donor's renal and urothelial cells (positive controls). No control patients had any evidence of transitional-cell carcinoma by cystoscopy. Our results provide objective evidence that non-invasive molecular detection of bladder TCC by microsatellite analysis is reproducible with a sensitivity of 83% and a specificity of 100% in Caucasian patients. This non-invasive procedure represents a potential clinical tool for the detection and the screening of bladder TCC. Int. J. Cancer (Pred. Oncol.) 79:629–633, 1998. © 1998 Wiley-Liss, Inc.     

Choriocarcinoma and transitional cell carcinoma of the bladder--a case report and review of the clinical evolution of disease in reported cases

The sixth reported case of choriocarcinoma associated with transitional cell carcinoma (TCC) of the bladder is described. A 67-year-old female presented with haematuria and was found to have a bladder tumour with both poorly differentiated TCC and trophoblastic elements. The tumour was confirmed as being limited to the bladder at laparotomy. The patient was treated with combination chemotherapy but, after an initial response, relapsed and died of disease. Postmortem examination revealed multiple metastatic choriocarcinoma and no TCC. A review of the clinical evolution in the reported cases suggests that transitional cell carcinoma is the cell of origin of these tumours by the process of progressive retrodifferentiation.     

Solitary meningeal recurrence in a patient with transitional cell carcinoma of the bladder with locally bulky disease at presentation

Patients with locally advanced transitional cell carcinoma (TCC)of the bladder are at high risk forsystemic relapse, with liver, bone and lung beingthe commonest sites of metastases.We report the case of a 52-year-old womanwith a solitary meningeal relapse, a rare siteof recurrence, after 8 months of complete remissionobtained with M-VEC for locally advanced TCC ofthe bladder. We speculate on the likely riskfactors related to this unusual site of recurrence.     

Quantitation of rare circulating tumor cells by folate receptor α ligand-targeted PCR in bladder transitional cell carcinoma and its potential diagnostic significance

Numerous attempts for detection of circulating tumor cells (CTC) have been made to develop reliable assays for early diagnosis of cancers. In this study, we validated the application of folate receptor α (FRα) as the tumor marker to detect CTC through tumor-specific ligand PCR (LT-PCR) and assessed its utility for diagnosis of bladder transitional cell carcinoma (TCC). Immunohistochemistry for FRα was performed on ten bladder TCC tissues. Enzyme-linked immunosorbent assay (ELISA) for FRα was performed on both urine and serum specimens from bladder TCC patients (n?=?64 and n?=?20, respectively) and healthy volunteers (n?=?20 and n?=?23, respectively). Western blot analysis and qRT-PCR were performed to confirm the expression of FRα in bladder TCC cells. CTC values in 3-mL peripheral blood were measured in 57 bladder TCC patients, 48 healthy volunteers, and 15 subjects with benign urologic pathologies by the folate receptor α ligand-targeted PCR. We found that FRα protein was overexpressed in both bladder TCC cells and tissues. The levels of FRα mRNA were also much higher in bladder cancer cell lines 5637 and SW780 than those of leukocyte. Values of FRα were higher in both serum and urine specimens of bladder TCC patients than those of control. CTC values were also higher in 3-mL peripheral blood of bladder TCC patients than those of control (median 26.5 Cu/3 mL vs 14.0 Cu/3 mL). Area under the receiver operating characteristic (ROC) curve for bladder TCC detection was 0.819, 95 % CI (0.738–0.883). At the cutoff value of 15.43 Cu/3 mL, the sensitivity and the specificity for detecting bladder cancer are 82.14 and 61.9 %, respectively. We concluded that quantitation of CTCs through FRα ligand-PCR could be a promising method for noninvasive diagnosis of bladder TCC.