Impact of divergent differentiation in urothelial carcinoma on oncological outcome in patients with T1 high-grade bladder cancer

Fujii, Nakanori; Hoshii, Yoshinobu; Hirata, Hiroshi; Mori, Junichi; Shimizu, Kosuke; Kobayashi, Keita; Kawai, Yosuke; Inoue, Ryo; Yamamoto, Yoshiaki; Matsumoto, Hiroaki; Nagao, Kazuhiro; Matsuyama, Hideyasu

doi:10.1093/jjco/hyx030

Cited by 9 publications

(11 citation statements)

References 31 publications

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“…The study has concluded that presence of diverse differentiation of UC at TURBT was an independent predictor of metastasis (P = 0.007) without remarkable association with survival prediction (Wasco et al, 2007). These study results agree with another study result that found a significant difference between divergent differentiation with squamous differentiation and pure UC in PFS, Recurrence-Free Survival (RFS), and Cancer-Specific Survival (CSS) (Fujii et al, 2017). Another study revealed the predominance of variant TCC with 51%.…”

Section: Discussionsupporting

confidence: 92%

Detection of Epithelial-Mesenchymal Transition Markers in High Grade Bladder Cancer and Special Variants of Urothelial Carcinoma

Khalil

Hammam

Kamel

2022

Asian Pac J Cancer Prev

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Transitional cell carcinoma is considered the most predominant type of bladder cancer. Bladder can cer can also be found as squamous cell carcinoma that accounts for 5% of the total bladder cancer due to its etiology. The biomarkers associated with grade, prognosis, and stage of the disease are not well proved and known however, many studies have pointed to the association between SNAL/SLUG and Twist2 to the overall survival in patients with bladder cancer. These biomarkers were found to have a crucial role in inhibiting cadherin mediators specifically E-cadherin which are found normally in high level to integrate cell adhesion and normal function of the bladder. This research aims to detect SNAL/SLUG and Twist2 biomarkers in specimens of patients with bladder cancer and to detect their impact on E-cadherin, a tumor suppressor mediator responsible for improving survival and prevent metastasis. Materials and Methods: Using 150 archival tissue blocks from human bladder cancer cases to detect expression of SNAIL/SLUG and Twist2 in relation to loss of E-cadherin by immunohistochemical method. Results: Our results have revealed that in squamous cell carcinoma 40 specimens showed marked Twist 2 expression, and 30 specimens showed marked snail/slug biomarkers expression while poorly differentiated cancer cases showed marked expression of Twist 2 in 60 specimens and marked expression of Snail/slug marked expression in 50 specimens. Both were associated with E-cadherin loss. Among the 100 specimens with transitional cell carcinoma, 70 specimens showed divergent differentiation with 7 subtypes each showed different medium to high expression of Snail/Slug and Twist 2 biomarkers with the loss of E-cadherin. E-cadherin was strongly associated with the inverse increase in SNAL/SLUG and Twist2 biomarkers in urothelial carcinoma. Conclusion: Detection of SNAIL/SLUG and Twist 2 biomarkers in urothelial cancer is an important predictor for the loss of E-cadherin, a cornerstone in urinary bladder cell adhesion and its loss in urothelial carcinoma may contribute to cancer invasion and poor prognosis.

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Section: Discussionsupporting

confidence: 92%

Detection of Epithelial-Mesenchymal Transition Markers in High Grade Bladder Cancer and Special Variants of Urothelial Carcinoma

Khalil

Hammam

Kamel

2022

Asian Pac J Cancer Prev

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“…Accordingly, a scarce response to BCG therapy has been reported by Gofrit et al [54], with lower 5-year survival rates compared to patients with pure HG UC (79.1 vs. 89.5%, respectively). In keeping with this, the presence of a squamous component was associated with a poorer prognosis than GD in T1-HG NMIBC conservatively treated with intravesical chemotherapy (mitomycin C, Adriamycin, pirarubicin) and BCG [76], and was a prognostic factor for recurrence and progression in a large series of 213 T1 NMIBC managed cases with intravesical chemotherapy (epirubicin or hydroxycamptothecin) [96].…”

Section: Squamous Differentiationsupporting

confidence: 53%

“…In two further studies on 41 VH-NMIBC cases (14 MV, 13 SD, 9 GD, 7 NV) and 62 SD/GD-NMIBC cases, respectively, treated with BCG, versus pure UC, the 5-year outcome rates (RFS, PFS, CSS, and OS) were poorer overall [54,75], reflecting decreased response rates to BCG as well as a lower chance for efficient salvage therapy after progression [54]. Accordingly, Fujii et al [76] reported on VH as the only independent predictor of both RFS and PFS in a cohort (59% GD, 29% GD, 12% SD + GD) of patients with T1-HG UC conservatively treated (intravesical chemotherapy, BCG). Recently, higher 2-year RFS after treatment with BCG was described in VH patients compared to pure UC at both univariate (62.1 vs. 38.0%, p < 0.05) and multivariate analysis (HR 0.43, 95% CI 0.25-0.73) [77].…”

Section: Nmibc With Vh: Critical Issuesmentioning

confidence: 98%

Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications

et al. 2021

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Background: The most common bladder cancer (BC) histotype is pure urothelial carcinoma (UC), which may undergo divergent differentiation in some cases. Variant histology (VH) presents along variable morphologies, either single or combined between them or with pure UC. From a clinical standpoint, the vast majority of BC is diagnosed at non-invasive or minimally invasive stages, namely as non-muscle invasive BC (NMIBC). There is a wide range of therapeutic options for patients with NMIBC, according to their clinical and pathological features. However, current risk stratification models do not show optimal effectiveness. Evidence from the literature suggests that VH has peculiar biological features, and may be associated with poorer survival outcomes compared to pure UC. Summary: In order to describe the biological features and prognostic/predictive role of VH in NMIBC, and to discuss current treatment options, we performed a systematic literature search through multiple databases (PubMed/Medline, Google Scholar) for relevant articles according to the following terms, single and/or in combination: “non-muscle invasive bladder cancer,” “variant histology,” “micropapillary variant,” “glandular differentiation,” “squamous differentiation,” “nested variant,” “plasmacytoid variant,” and “sarcomatoid variant.” We extracted 99 studies including original articles, reviews, and systematic reviews, and subsequently analyzed data from 16 studies reporting on the outcome of NMIBC with VH. We found that the relative rarity of these forms as well as the heterogeneity in study populations and therapeutic protocols results in conflicting findings overall. Key Messages: The presence of VH should be taken into account when counseling a patient with NMIBC, since it may upgrade the disease to high-risk tumor and thus warrant a more aggressive treatment.

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“…The present study indicated that a larger tumor size (>3.5 cm) was an independent prognostic factor in patients with T1HG BC. A previous study indicated that recurrence, progression and poorer survival rates were more common in patients with larger tumors (26). In the present study, the marital status had a significant prognostic value.…”

Section: Discussionmentioning

confidence: 97%

Application of nomograms in the prediction of overall survival and cancer‑specific survival in patients with T1 high‑grade bladder cancer

Tang

et al. 2019

Exp Ther Med

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To predict survival outcomes for individual patients with clinical T1 high-grade (T1HG) bladder cancer (BC), data from the Surveillance Epidemiology and End Results (SEER) database were analyzed in the present study. The data of 6,980 cases of T1HG BC between 2004 and 2014 were obtained from the SEER database. Uni- and multivariate Cox analyses were performed to identify significant prognostic factors. Subsequently, prognostic nomograms for predicting 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were constructed based on the SEER database. Clinical information from the SEER database was divided into internal and external groups and used to validate the nomograms. In addition, calibration plot diagrams and concordance indices (C-indices) were used to verify the predictive performance of the nomogram. A total of 6,980 patients were randomly allocated to the training cohort (n=4,886) or the validation cohort (n=2094). Univariate and multivariate Cox analyses indicated that age, ethnicity, tumor size, marital status, radiation and surgical status were independent prognostic factors. These characteristics were used to establish nomograms. The C-indices for OS and CSS rate predictions for the training cohort were 0.707 (95% CI, 0.693–0.721) and 0.700 (95% CI, 0.679–0.721), respectively. Internal and external calibration plot diagrams exhibited an excellent consistency between actual survival rates and nomogram predictions, particularly for 3- and 5-year OS and CSS. The significant prognostic factors in patients with T1HG BC were age, ethnicity, marital status, tumor size, status of surgery and use of radiation. In the present study, a nomogram was developed that may serve as an effective and convenient evaluation tool to help surgeons perform individualized survival evaluations and mortality risk determination for patients with T1HG BC.

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Impact of divergent differentiation in urothelial carcinoma on oncological outcome in patients with T1 high-grade bladder cancer

Cited by 9 publications

References 31 publications

Detection of Epithelial-Mesenchymal Transition Markers in High Grade Bladder Cancer and Special Variants of Urothelial Carcinoma

Detection of Epithelial-Mesenchymal Transition Markers in High Grade Bladder Cancer and Special Variants of Urothelial Carcinoma

Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications

Application of nomograms in the prediction of overall survival and cancer‑specific survival in patients with T1 high‑grade bladder cancer

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