Fang Jian Zhou

Expression of Bmi-1 is a prognostic marker in bladder cancer.

BackgroundThe molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer.MethodsWe examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis.ResultsExpression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P < 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (P < 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (P < 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, P < 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, P > 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P < 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (P < 0.05), but not with tumor number (P > 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P < 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer survival time (P < 0.05).ConclusionExpression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

Modified Technique of Radical Inguinal Lymphadenectomy for Penile Carcinoma: Morbidity and Outcome

PURPOSEnClassic radical inguinal lymphadenectomy is associated with significant morbidity. Modified inguinal lymphadenectomy has been used to decrease the complication rate but it may compromise the oncological effect and depends on the use of intraoperative frozen sections, which may be inaccurate. We modified the technique of radical inguinal lymphadenectomy to decrease postoperative complications without compromising oncological effectiveness.nnnMATERIALS AND METHODSnWe performed 150 modified radical inguinal dissections in 75 patients with penile carcinoma from February 1999 to September 2008. Patients underwent modified radical inguinal dissection characterized by an S-shaped incision, precisely separating layers using an anatomical landmark and preserving the fascia lata. The boundaries of dissection are the same as those of radical inguinal lymphadenectomy. Survival and morbidity data were retrospectively analyzed, and survival probabilities were calculated.nnnRESULTSnFollowup ranged from 12 to 113 months. Overall 3-year survival was 92%, and for N0, N1, N2 and N3 disease it was 100%, 100%, 85% and 57.1%, respectively. A total of 37 complications occurred including wound infection (1.4%), skin necrosis (4.7%), lymphedema (13.9%), seroma (2.0%), lymphocele (2.0%) and deep venous thrombosis (0.7%).nnnCONCLUSIONSnMorbidity related to groin dissection in patients with penile carcinoma can be decreased and oncological effectiveness can be preserved using this modified inguinal dissection technique.

Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder

BackgroundYes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.MethodsIn this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate mRNA/ protein expression of YAP 1 in UCBs. Spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.ResultsUp-regulated expression of YAP 1 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blotting, when compared with their paired normal bladder tissues. By IHC, positive expression of YAP 1 was examined in 113/213 (53.1%) of UCBs and in 6/86 (7.0%) of normal bladder specimens tissues. Positive expression of YAP 1 was correlated with poorer differentiation, higher T classification and higher N classification (P < 0.05). In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients’ survival was found (P < 0.001). In different subsets of UCB patients, YAP 1 expression was also a prognostic indicator in patients with grade 2 (P = 0.005) or grade 3 (P = 0.046) UCB, and in patients in pT1 (P = 0.013), pT2-4 (P = 0.002), pN- (P < 0.001) or pT2-4/pN- (P = 0.004) stage. Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis.ConclusionsOur findings provide evidences that positive expression of YAP 1 in UCB may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with UCB.

Overexpression of EIF-5A2 Is an Independent Predictor of Outcome in Patients of Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy

Background: Our previous study has suggested an oncogenic role of eIF-5A2 in ovarian tumorigenesis. Abnormalities of eIF-5A2 and its clinical/prognostic significance, however, in urothelial carcinoma of the bladder (UC) are unclear. Methods: In this study, the methods of reverse transcription-PCR, immunohistochemistry, and fluorescence in situ hybridization were used to examine mRNA/protein expression and amplification of eIF-5A2 in a large cohort of UCs treated with radical cystectomy. Results: Up-regulated expression of eIF-5A2 mRNA was observed in 50% (8 of 16) of UCs, when compared with adjacent normal bladder tissues. Overexpression of EIF-5A2 protein and amplification of eIF-5A2 was examined informatively in 45.3% (39 of 86) and 10.6% (5 of 47) of UCs, respectively. In univariate survival analysis of the UC cohorts, a significant association of overexpression of EIF-5A2 with shortened patient survival (mean, 38.2 months versus 52.9 months, P = 0.001, log-rank test) was shown. In different subsets of UC patients, overexpression of EIF-5A2 was also a prognostic indicator in grade 1/2 (P = 0.0009) and grade 3 (P = 0.016) tumor patients, and in pT1 (P = 0.0089), pT2 (P = 0.0354), pT3/4 (P = 0.0058), pN0 (P = 0.0039), and pN1-2 (P = 0.0093) tumor patients. Importantly, EIF-5A2 expression (P = 0.0007) together with pT stage (P = 0.0001) provided significant independent prognostic variables in multivariate analysis. Conclusions: These findings indicate that overexpression of EIF-5A2 in UCs is coincident with acquisition of a poor prognostic phenotype, suggesting that the expression of EIF-5A2, as detected by immunohistochemistry, is an independent molecular marker for shortened survival time of UC patients treated with radical cystectomy. (Cancer Epidemiol Biomarkers Prev 2009;18(2):400–8)

The risk factors for the presence of pelvic lymph node metastasis in penile squamous cell carcinoma patients with inguinal lymph node dissection

ObjectiveTo evaluate factors in penile squamous cell carcinoma predictive of pelvic lymph node metastasis and survival.Materials and methodsData were collected and analyzed retrospectively in 146 patients with squamous cell carcinoma of penis who underwent bilateral inguinal lymph node dissection in our center between January 1998 and April 2011. Variables recorded included serum squamous cell carcinoma antigen, primary tumor p53 immunoreactivity, histological grade, pathological tumor stage, lymphatic or vascular invasion, absent/unilateral or bilateral inguinal lymph node involvement, number of metastatic inguinal lymph nodes, presence of extracapsular growth and lymph node density.ResultsSeventy patients had inguinal lymph node metastasis (LNM). Of these, 33 (47.1xa0%) had pelvic LNM. Primary tumor strong p53 expression, lymphatic or vascular invasion, involvement of more than two inguinal lymph nodes and 30xa0% or greater lymph node density were significant predictors of pelvic LNM. Primary tumor strong p53 expression (odds ratio [OR] 5.997, 95xa0% confidence intervals [CI] 1.615–22.275), presence of extracapsular growth (OR 2.209, 95xa0% CI 1.166–4.184), involvement of more than two inguinal lymph nodes (OR 2.494, 95xa0% CI 1.086–5.728) and pelvic lymph node involvement (OR 18.206, 95xa0% CI 6.807–48.696) were independent prognostic factors for overall survival.ConclusionsPrimary tumor expression of p53, lymphatic or vascular invasion, number of metastatic inguinal lymph nodes and lymph node density were all predictors of pathologic pelvic lymph node involvement. Patients with pelvic LNM had an adverse prognosis, with a 3-year overall survival rate of approximately 12.1xa0%. Pelvic lymph node dissection should be considered in these cases.

PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16/cyclin D1 pathway

BackgroundPIN2/TRF1-interacting telomerase inhibitor1 (PinX1) was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase. Moreover, loss of PinX1 has been detected in many human malignancies. However, the possible involvement of PinX1 and its clinical/prognostic significance in urothelial carcinoma of the bladder (UCB) are unclear.MethodsThe PinX1 expression profile was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry (IHC) in UCB tissues and adjacent normal urothelial bladder epithelial tissues. PinX1 was overexpressed and silenced in UCB cell lines to determine its role in tumorigenesis, development of UCB, and the possible mechanism.ResultsPinX1 expression in UCB was significantly down-regulated at both mRNA and protein level as compared with that in normal urothelial bladder epithelial tissues. PinX1 levels were inversely correlated with tumor multiplicity, advanced N classification, high proliferation index (Ki-67), and poor survival (Pu2009<u20090.05). Moreover, overexpression of PinX1 in UCB cells significantly inhibited cell proliferation in vitro and in vivo, whereas silencing PinX1 dramatically enhanced cell proliferation. Overexpression of PinX1 resulted in G1/S phase arrest and cell growth/proliferation inhibition, while silencing PinX1 led to acceleration of G1/S transition, and cell growth/proliferation promotion by inhibiting/enhancing telomerase activity and via the p16/cyclin D1 pathway.ConclusionsThese findings suggest that down-regulation of PinX1 play an important role in the tumorigenesis and development of UCB and that the expression of PinX1 as detected by IHC is an independent molecular marker in patients with UCB.

Benign pathological findings in 303 Chinese patients undergoing surgery for presumed localized renal cell carcinoma

Objective:u2003 To analyze the incidence of benign lesions in Chinese patients undergoing nephrectomies for renal masses identified as localized renal cell carcinoma (RCC) in preoperative imaging.

Disease-specific survival after radical lymphadenectomy for penile cancer: Prediction by lymph node count and density

OBJECTIVEnTo investigate the value of removed lymph node (LN) count and LN density (LND) for predicting disease-specific survival (DSS) rate following radical lymphadenectomy in patients with penile cancer.nnnMETHODSnWe retrieved data from 146 patients who were surgically treated between 2002 and 2012. receiver-operating characteristic curve analysis was used to calculate the optimal cutoff value of LN count and LND for predicting DSS rate. LND was analyzed as a categorical variable by grouping patients with pN+tumors into 2 categories. Multivariate Cox regression analysis was used to test the effect of various variables on DSS rate based on collinearity in various models.nnnRESULTSnMedian follow-up was 42 months. Overall, 75 patients (51.4%) had pN0 disease, and 71 patients (48.6%) had pN+disease. The optimal cutoff value of LN count and LND were 16% and 16%, respectively. Among patients with pN0 tumors, the number of LNs removed (≥16 LNs) was an independent significant predictor of DSS rate in univariate and multivariate analyses (all P<0.05). Stratifying pN+ patients as above versus below the LND threshold demonstrated significant differences in 5-year DSS: 81.2% versus 24.4% (P < 0.001). In multivariate models including known prognostic factors, LND was a statistically significant independent predictor of DSS rate (hazard ratio = 4.31 and 3.96 for above vs. below the LND threshold, respectively).nnnCONCLUSIONSnThe removal of at least 16 LNs was associated with a significantly longer DSS rate in patients with pN0 penile cancer. Additionally, an LND above 16% is an independent predictor of DSS rate in patients with pN+tumors. Further independent validation is required to determine the clinical usefulness of LN count and LND in this patient population.

Fascia Lata Preservation During Inguinal Lymphadenectomy for Penile Cancer: Rationale and Outcome

OBJECTIVEnTo investigate local groin recurrence and morbidity associated with fascia lata preservation during inguinal lymphadenectomy (LAD) for penile carcinoma.nnnMETHODSnBetween January 2002 and December 2011, 201 inguinal dissections with preservation of the fascia lata were performed in 104 patients with clinical disease staged at ≤N2. The dissection boundaries were the same as those for radical inguinal LAD. All superficial inguinal nodes were removed en bloc. The cribriform fascia near the femoral canal was divided, and the deep inguinal lymph nodes were dissected. The fascia lata was completely preserved and sutured to the subcutaneous tissue. Sartorius muscle transposition was eliminated. Survival and morbidity data were retrospectively analyzed, and survival probabilities were calculated.nnnRESULTSnThe median operative time for unilateral inguinal LAD was 45 minutes (range, 40-60 minutes). Median follow-up was 36 months (range, 10-130 months). A mean number of 12.5 nodes were removed per groin. One patient (1%) had a recurrence outside the borders of the fascia lata after 7 months of follow-up. The 3-year disease-free survival rate was 92.1% (100% for pN0, 91.3% for pN1, 80% for pN2, and 33.3% for pN3 disease). A total of 59 complications (29.3%) occurred, including wound infection (2.5%), skin necrosis (5.5%), lymphedema (11.8%), seroma formation (1.5%), lymphocele (5%), paresthesia (3.5%), and deep venous thrombosis (0.5%).nnnCONCLUSIONnInguinal dissections with preservation of the fascia lata for penile carcinoma patients without extranodal extension is as effective as the classic dissection technique but decreases complications related to groin dissection.

Renal plasmacytoma: Report of a rare case and review of the literature

Renal plasmacytoma is extremely rare, presenting diagnostic challenges due to its unusual location and non-specific or absent symptoms. To the best of our knowledge, only 24 cases of renal plasmacytoma have been reported in the literature. The present study reports a case of primary renal plasmacytoma in a 46-year-old female patient. Computed tomography (CT) revealed that the mass was located in the lower pole of the left kidney and metastasis was detected in an enlarged para-aortic lymph node. Following careful preparation, a partial nephrectomy was performed and the retroperitoneal lymph node was resected. A pathological examination revealed a renal parenchyma with lymph node involvement; this was confirmed by immunohistochemistry and nested polymerase chain reaction (PCR). Consequently, a diagnosis of a renal extramedullary plasmacytoma (EMP) was proposed. Following this unexpected diagnosis, various examinations were performed, but there was no evidence of systemic plasma cell disease. The patient refused further therapy, including external beam radiotherapy and chemotherapy. Abdominal CT was performed three months post-surgery and did not reveal any relapse. The patient remains disease-free at nine months post-surgery. The current study also presents a review of the literature. Although the general prognosis and outcome of EMP is good, a follow-up examination is recommended due to the possibility of relapse or progression to plasma cell neoplasm (PCN).