Focal S100A4 Protein Expression Is an Independent Predictor of Development of Metastatic Disease in Cystectomized Bladder Cancer Patients

370 Background: Neoadjuvant chemotherapy is associated with improved overall survival benefit and the concept of systemic therapy followed by local consolidation may also lead to favorable long-term outcomes for those with lymph node (LN) metastases at presentation. Our goal was to examine the outcome of preoperative chemotherapy in patients (pts) with and without clinical evidence of LN metastases. Methods: After informed consent, patients were enrolled in a prospective database prior to radical cystectomy with lymph node dissection for bladder cancer between December 2001 to February 2014. Data were analyzed using descriptive statistics. Results: Our cohort included 63 patients receiving pre-operative chemotherapy with a median age 68 (range 38-91), 46 (72%) were male, and 17 (27%) had gross metastatic disease to lymph nodes (LNs). 13 pts received MVAC (20%), 44 gemcitabine and cisplatin (GC) (69%), 1 gemcitabine and carboplatin, 1 received ifosfamide, paclitaxel, and cisplatin and 4 pts had unknown neoadjuvant chemo outside of the institution. Most patients with LN positive (71%) disease received GC preoperative regimens. The median and the modal number of cycles were 4 (range 1-6). 44 patients underwent robotic-assisted radical cystectomy (RARC) (69%), 19 underwent open radical cystectomy (30%), and another pt. had RARC converted to an open procedure. Overall, 20 (31%) patients achieved pathologic complete response (pCR). Four pts (24%) with initial metastatic disease achieved pCR after preoperative chemotherapy. Overall pCR rates were similar between MVAC (38%) and GC (33%). All LN positive patients who achieved pCR had received gemcitabine-cisplatin preoperatively and underwent RARC. Recurrence-free and overall-survival data will be presented at the meeting. Conclusions: Preoperative chemotherapy was associated with a significant pCR rate in all bladder cancer patients including LN positive patients.

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Nuclear cIAP1 overexpression is a tumor stage- and grade-independent predictor of poor prognosis in human bladder cancer patients

Urologic Oncology Seminars and Original Investigations ◽

10.1016/j.urolonc.2010.12.016 ◽

2012 ◽

Vol 30 (4) ◽

pp. 450-456 ◽

Cited By ~ 23

Author(s):

Xiangyu Che ◽

Deyong Yang ◽

Huafeng Zong ◽

Jianbo Wang ◽

Xiancheng Li ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Patients ◽

Poor Prognosis ◽

Independent Predictor ◽

Tumor Stage ◽

Human Bladder Cancer ◽

Human Bladder

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The prognostic impact of GSTM1/GSTP1 genetic variants in bladder Cancer

BMC Cancer ◽

10.1186/s12885-019-6244-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Nada Albarakati ◽

Dareen Khayyat ◽

Asharf Dallol ◽

Jaudah Al-Maghrabi ◽

Taoufik Nedjadi

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Protein Expression ◽

Cancer Patients ◽

Genetic Variants ◽

Clinicopathological Parameters ◽

Wild Type ◽

Poor Survival ◽

Her2 Protein ◽

Kaplan Meier

Abstract Background The glutathione S-transferases (GSTs) are a superfamily of phase II detoxifying enzymes that inactivates a wide variety of potential carcinogens through glutathione conjugation. Polymorphic changes in the GST genes have been reported to be associated with increased susceptibility to cancer development and anticancer drug resistance. In this study, we investigated the association between genetic variants in GSTM1 and GSTP1 and patients’ clinicopathological parameters. The prognostic values of such associations were evaluated among bladder cancer patients. Methods Genotyping of GSTM1 and GSTP1 in bladder cancer patients was assessed using polymerase chain reaction followed by DNA sequencing. Overall survival was estimated using the Kaplan-Meier method and multiple logistic regression and correlation analysis were performed. Results The GSTM1 null genotype was significantly associated with poor overall survival compared with the wild-type GSTM1 genotype. There was a trend towards better overall survival in patients with wild-type GSTP1 allele (AA) compared with GSTP1 (AG/GG) genotype. Interestingly, Kaplan-meier survival curve for GSTM1 null patients adjusted for sub-cohort with amplified HER2 gene showed poor survival compared with the GSTM1 null/ non-amplified HER2 gene. Also the same population when adjusted with HER2 protein expression, data showed poor survival for patients harboring GSTM1 null/high HER2 protein expression compared with low protein expression. Conclusion This study focuses on the impact of GSTM1 null genotype on bladder cancer patients’ outcome. Further investigations are required to delineate the underlying mechanisms of combined GSTM−/− and HER2 status in bladder cancer.

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Relationship between S100A4 protein expression and pre-operative serum CA19.9 levels in pancreatic carcinoma and its prognostic significance

World Journal of Surgical Oncology ◽

10.1186/s12957-019-1707-4 ◽

2019 ◽

Vol 17 (1) ◽

Author(s):

Fuxin Jia ◽

Mengmeng Liu ◽

Xiao Li ◽

Fen Zhang ◽

Shuqiang Yue ◽

...

Keyword(s):

Overall Survival ◽

Protein Expression ◽

Pancreatic Carcinoma ◽

Poor Prognosis ◽

Independent Predictor ◽

False Negative ◽

Prognostic Significance ◽

Clinicopathological Parameters ◽

S100a4 Protein ◽

S100a4 Expression

Abstract Background Pancreatic carcinoma (PC) is one of the most lethal malignancies, and its poor prognosis is strongly associated with invasion and metastasis. CA19.9 is considered to be the most sensitive serum marker for PC in clinical practice; however, the detection of CA19.9 in PC has a certain false positive and false negative rate. The expression of the calcium-binding protein S100A4 has been reported to be associated with poor prognosis in various cancers. This study aimed to investigate the relationship between S100A4 and CA19.9 and its prognostic significance in PC. Methods We performed immunohistochemical staining for S100A4 in formalin-fixed, paraffin-embedded blocks of 128 PC tissues. The levels of S100A4 expression and pre-operative serum CA19.9 were correlated with clinicopathological parameters. The possible correlation between S100A4 protein expression and pre-operative serum CA19.9 levels were evaluated using the chi-square test and Spearman correlation. Survival was assessed by Kaplan–Meier analysis together with a single variable or multivariate Cox analysis. Results A significant positive correlation between S100A4 expression and pre-operative serum CA19.9 level was observed in PC tissues (ρ = 0.202, P = 0.022). The co-expression of both proteins correlated significantly with tumor differentiation (ρ = − 0.280, P = 0.001), TNM stage (ρ = − 0.389, P = 0.000), and lymph node metastasis (ρ = 0.254, P = 0.008). Upregulation of S100A4 was identified as a significant, independent predictor of poor overall survival (P = 0.000). Moreover, higher serum CA19.9 levels (≥ 35 U/mL) were also recognized as an independent predictor of inferior overall survival (P = 0.001). Additionally, upregulation of S100A4 and higher pre-operative serum CA19.9 levels (≥ 35 U/mL) in patients with PC contributed to a significant decrease in overall survival (P = 0.000). Conclusions The expression levels of S100A4 in PC tissues were positively correlated with pre-operative serum CA19.9 levels. S100A4 expression and pre-operative serum CA19.9 levels were significant, independent prognostic factors for the overall survival of patients with PC. S100A4 expression/pre-operative serum CA19.9 levels may prove useful as dual prognostic biomarkers for PC. Analysis of CA19.9 in combination with S100A4 can better predict the prognosis of PC.

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