scholarly journals Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0259272
Author(s):  
Esmail M. Al-ezzi ◽  
Zachary W. Veitch ◽  
Samer H. Salah ◽  
Theodorus H. Van der Kwast ◽  
Tracy L. Stockley ◽  
...  

Background Non-schistosomiasis related-squamous cell carcinoma of urinary bladder (NSR-SCCUB) is a rare tumor subtype distinct from urothelial carcinoma (UC). Studies assessing molecular biomarkers in bladder cancer have generally focused on UC, and genomic data of NSR-SCCUB is limited. We aim to provide additional insight into the molecular underpinnings of this rare entity. Methods NSR-SCCUB patients were identified retrospectively at Princess Margaret Cancer Centre between 2002 and 2017. Demographics, disease characteristics, therapeutic approaches, and outcomes were collected. Tissue samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Kaplan-Meier method was used to estimate the disease-free survival and overall survival (OS). Results Overall, 11 patients with NSR-SCCUB were identified between 2002 and 2017 with adequate tissue samples. Median age was 71 years (45–86), predominantly male (63.6%). At time of diagnosis, 9 patients (81.8%) had muscle-invasive disease, 1 (9.1%) had non-muscle invasive, and 1 (9.1%) had advanced disease. Nine (81.8%) patients had radical cystectomy and pelvic lymph nodes dissection. Eight (72.7%) patients had pT3 or pT4 with N0, and 5 (45.5%) were grade 3. Median OS was 12.5 months (95% CI 7.7–17.2 months). Single nucleotide variants or insertion/deletions were identified in TP53, TERT, PIK3CA, PTEN, CREBBP, FBXW7, and FGFR3. Amplifications were found in CCND1, and EGFR. Conclusions NSR-SCCUB has potentially actionable genomic alterations with anticancer agents and many of these aberrations are also seen in UC. The recruitment of NSR-SCCUB patients harboring such mutations should be considered in biomarker driven urinary bladder cancer studies.

Author(s):  
Sunil Vitthalrao Jagtap ◽  
Swati S Jagtap ◽  
Parneet Kaur ◽  
Snigdha Vartak

Urinary bladder cancer is one of the most prevalent cancers worldwide.Squamous Cell Carcinoma (SCC) is an uncommon subtype of urinary bladder carcinoma.It is a malignant epithelial neoplasm arising in the urinary bladder demonstrating a pure squamous cell phenotype. On histopathology it is considered when tumor is showing pure squamous morphology without any component of conventional urothelial carcinoma. The SCC is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of cells showing particular cytological or tissue architectural characteristics of squamous cell differentiation, such as the presence of keratin, tonofilament bundles or desmosomes. Majority of bladder SCC are high grade, high stage tumors with most cancers having muscle invasion at the time of diagnosis while overall about 80% of bladder cancers are non-muscle invasive bladder cancer at diagnosis.COX-2 is markedly expressed in all SCCs. An increased COX-2 level induces the development of SCC of the bladder affecting many biological features of this tissue including apoptosis, cell adhesion, angiogenesis and invasiveness.TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorgenesis and potential utility as a molecular urine-based-screening assay.This review summarizes the current features related to clinical , pathological, and molecular features of SCC of urinary bladder.


2003 ◽  
Vol 18 (4) ◽  
pp. 284-289 ◽  
Author(s):  
A. El-Meghawry El-Kenawy ◽  
A.F. El-Kott ◽  
A.M. Khalil

The aim of this study was to elucidate the associations between immunostaining for MDM2 and p53, their respective expression in squamous cell carcinoma of the urinary bladder, and the value of these variables for predicting treatment outcome after cystectomy. Inactivation of TP53 might play a role in the development and progression of bladder cancer. Complex formation with the MDM2 product is one mechanism that inactivates the p53 protein. Therefore, the MDM2 and the p53 protein were investigated to study potential interactions in bladder cancer. Fifty archival bladder tissue specimens were immunohistochemically stained using monoclonal antibodies against p53 and MDM2. Staining for p53 was observed in 48% of the specimens and staining for MDM2 in 20%. Univariate analysis demonstrated a significant correlation between p53 accumulation and survival (p=0.0101), while the correlation between MDM2 and survival was not significant (p=0.7183). The combined expression of MDM2 and p53 doest not add to the prognostic information provided by p53 alone.


Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 90
Author(s):  
Guglielmo Mantica ◽  
Francesco Chierigo ◽  
Rafaela Malinaric ◽  
Salvatore Smelzo ◽  
Francesca Ambrosini ◽  
...  

Background and Objectives: To evaluate the oncological impact of squamous cell carcinoma (SCC) variant in patients submitted to intravesical therapy for non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: Between January 2015 and January 2020, patients with conventional urothelial NMIBC (TCC) or urothelial NMIBC with SCC variant (TCC + SCC) and submitted to adjuvant intravesical therapies were collected. Kaplan–Meier analyses targeted disease recurrence and progression. Uni- and multivariable Cox regression analyses were used to test the role of SCC on disease recurrence and/or progression. Results: A total of 32 patients out of 353 had SCC at diagnosis. Recurrence was observed in 42% of TCC and 44% of TCC + SCC patients (p = 0.88), while progression was observed in 12% of both TCC and TCC + SCC patients (p = 0.78). At multivariable Cox regression analyses, the presence of SCC variant was not associated with higher rates of neither recurrence (p = 0.663) nor progression (p = 0.582). Conclusions: We presented data from the largest series on patients with TCC and concomitant SCC histological variant managed with intravesical therapy (BCG or MMC). No significant differences were found in term of recurrence and progression between TCC and TCC + SCC. Despite the limited sample size, this study paves the way for a possible implementation of the use of intravesical BCG and MMC in NMIBC with histological variants.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6057-6057
Author(s):  
Zhuo Georgia Chen ◽  
Sreevinas Nannapaneni ◽  
Christopher C Griffith ◽  
Dongsheng Wang ◽  
Chao Zhang ◽  
...  

6057 Background: Fibroblast growth factor receptor 3 (FGFR3) is expressed in squamous cell carcinoma of the head and neck (SCCHN) including oropharyngeal squamous cell carcinoma (OPSCC) and is a potential therapeutic target. Information on its prognostic value and its correlation with other relevant cancer related proteins is limited. Methods: We performed immunohistochemistry (IHC) analyses of p16, mutant p53 (mp53), and FGFR3 on 221 retrospectively collected OPSCC tissue samples. mp53, and FGFR3 were semi-quantified as weighted index [WI = % positive x intensity (0. 1+, 2+, and 3+)]. Correlations of FGFR3 WI with p16 status, and mp53 WI were analyzed. Association of FGFR3 with disease-free survival (DFS) or overall survival (OS) was assessed. Results: A total of 144/221 (65%) were p16 +, 93/172 (54%) had mp53, and 140/221 (63%) expressed FGFR3. FGFR3 was highly correlated with mp53 (p < 0.001), which was true in both p16 + and – OPSCC (p < 0.0001 and p = 0.0006, respectively).mp53 level was significantly lower in p16 positive versus p16 negative group (p < 0.0001). Univariate analysis revealed an association of p16 negative and high mp53 with worse OS (p < 0.001 and p < 0.001, respectively) and DFS (p < 0.001 and p = 0.004, respectively). FGFR3 was associated with worse OS and DFS (p = 0.014 and p = 0.047, respectively). On multivariable analysis FGFR3 was associated with worse DFS (p = 0.005), but not OS. Kaplan-Meier plot using medians of both FGFR3 and mp53 as the cut-off values showed that higher FGFR3 and mp53 correlated to worst DFS (p = 0.025) and OS (p = 0.009). Conclusions: Our results suggest that FGFR3 is associated with mp53 and p16 – OPSCC and correlates with worse clinical outcome. The biologic relation of FGFR3 and mp53 in OPSCC deserves further investigation. (This research was supported by a grant NCI R21 CA182661-01A1to NFS and GZC).


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