The prognostic value of E‐cadherin, α‐, β‐ and γ‐catenin in bladder cancer patients who underwent radical cystectomy

Kashibuchi, Keishi; Tomita, K.; Schalken, Jack A.; Kume, Haruki; Takeuchi, Takumi; Kitamura, Tadaichi

doi:10.1111/j.1442-2042.2007.01830.x

Cited by 23 publications

(21 citation statements)

References 22 publications

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“…Similar results regarding the significance of Á-catenin as a potential tumor suppressor protein in oral squamous cell carcinoma (24), non-small lung cancer (25) and bladder cancer (26) have been reported.…”

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confidence: 83%

Reduced expression of catenin subtypes is a potential indicator of unfavorable prognosis in esophageal squamous cell carcinoma

et al. 2009

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Abstract. Catenins are cytoplasmic proteins that play a pivotal role in cell adhesion. Conflicting results regarding the significance of their expression in esophageal squamous cell carcinoma (ESCC) have been reported. The expression of ·-, ß-and Á-catenin was examined using immunohistochemical methods in 69 samples collected from patients with ESCC who were surgically treated without any preoperative induction therapy. Reduced ·-, ß-and Á-catenin expression was observed in 48 (69.7%), 36 (52.2%) and 44 (63.8%) ESCC samples, respectively. According to univariate analysis, ESCC patients exhibiting the reduced expression of ß-catenin (P=0.028), Á-catenin (P=0.010), ·-and Á-catenin combined (P=0.047) or ß-and Á-catenin combined (P=0.046) had a significantly more unfavorable rate of survival. Multivariate analysis demonstrated that the reduced expression of Á-catenin (P=0.015) as well as lymph node metastasis (P=0.015) could serve as independent prognostic indicators of unfavorable prognosis in ESCC patients. Reduced immunohistochemical expression of Á-catenin may thus prove to be a powerfull and useful predictor of prognosis in patients with ESCC. IntroductionThe migration of cancer cells from the cancer nest is an initial event in the formation of tumor metastasis (1). Previous investigations have demonstrated that the expression of adhesion molecules, which prevent cancer cells from detaching, is a potential indicator of favorable prognosis in patients and/or of less invasive behavior in gastrointestinal cancer types, including esophageal squamous cell carcinoma (ESCC) (2-4).Among the various adhesion molecules, the expression of E-cadherin has primarily been investigated, and a significant correlation between its expression and a favorable prognosis in cancer patients, including those with ESCC, has been reported (5-7).Catenins (·-, ß-and Á-) are cytoplasmic proteins that bind to the conserved tail of the epithelial E-cadherin molecule and play a crucial role in E-cadherin-mediated intracellular signal transduction and cell adhesion. The cytoplasmic domain of E-cadherin binds to ß-or Á-catenin, while ·-catenin binds to the E-cadherin -ß-and -Á-catenin complexes to maintain the cellular cytoskeleton (8).While the immunohistochemical expression of ·-, ß-and Á-catenin in ESCC has been examined, the results reported regarding their clinicopathological significance for patient prognosis have been inconsistent (5,6,9-13). The present study used surgically dissected samples of ESCC to investigate the immunohistochemical expression of ·-, ß-and Á-catenin in order to determine their combined effect on the prognosis of patients with ESCC. Patients and methodsPatients and samples. Sixty-nine consecutive specimens of ESCC from patients surgically treated in our department between 1992 and 2003 were obtained. The study population consisted of 63 men and 6 women with a median age of 64 years (range 42-83). Preoperative induction therapy was not performed in any of the cases. Continuous follow-up of the patients was carried ou...

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confidence: 83%

Reduced expression of catenin subtypes is a potential indicator of unfavorable prognosis in esophageal squamous cell carcinoma

et al. 2009

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“…Kashibuchi et al showed a correlation between aberrant β-catenin and γ-catenin expression with tumor stage and a correlation between γ-catenin with tumor grade in urothelial bladder carcinomas. Furthermore, they found that abnormal expression of E-cadherin was an independent predictor of disease-specific survival in this neoplasia (11). Different from them, we tried to add details to the pattern of immune expression, stratifying the intensity of staining in weak, moderate and strong patterns.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor size has also been used as a criteria to proceed with more aggressive treatment in pT1-stage bladder cancer (23,24). Negative expression of this catenin has been related to worse prognosis, tumor stage, tumor grade and UC disease recurrence in other studies (11,25). However, there were no studies of α-catenin expression in UUCs.…”

Section: Discussionmentioning

confidence: 99%

“…Dysfunctions in cell-cell adhesion molecules have been related to the initial steps of tumor invasion and the development of metastasis in urothelial bladder carcinomas. Recently, Kashibuchi et al (11) demonstrated aberrant expression of E-cadherin and α-, β-and γ-catenin in 40 to 50% of urothelial bladder carcinoma cases. They also related aberrant expression to tumor stage and cancer specific survival.…”

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Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

et al. 2012

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ARTIcLE INFO _________________________________________________________ ___________________Introduction: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and α-, β-and γ-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. Materials and Methods: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. Results: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). Conclusions: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of α-catenin expression is related to tumor size in upper tract urothelial carcinomas.

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“…A decrease or lack of E-cad expression is associated with an advanced stage of UCB with higher risk of regional lymph node metastasis and inferior survival rates [13]. …”

Section: Introductionmentioning

confidence: 99%

Outcome of Patients with Pathological Tumor Stage T3 Urothelial Carcinoma of the Bladder following Radical Cystectomy in a Single-Center Series with 116 Patients

Breyer¹,

Denzinger²,

Otto³

et al. 2014

Urol Int

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Objective: Outcome prediction of pT3 urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) remains challenging. The objective of our study was to determine high-risk patients with poor survival outcome in a heterogeneous group substaged pT3 who might profit from early adjuvant chemotherapy. Materials and Methods: We compiled clinicopathological and immunohistochemical data of E-cadherin (E-cad) expression in 116 patients with pT3 UCB after RC in our single-center series. Multivariable Cox regression models including substaged pT3 established clinicopathological features, and the expression of the predictive immunohistochemical feature E-cad was used to identify independent predictors on progression-free (PFS), cancer-specific (CSS) and overall survival (OS), respectively. Results: No significant differences were found addressing clinicopathological data and substaged pT3. In multivariable Cox regression models, lymph node involvement was an independent predictor for PFS (p < 0.001), CSS (p < 0.001) and OS (p = 0.002), respectively. Lymphovascular invasion (LVI) significantly influenced PFS (p = 0.016). ASA score 3/4 independently predicted CSS (p = 0.049) and OS (p = 0.032). Neither pT3 substages nor E-cad expression were significant prognosticators for survival. Conclusions: In pT3 UCB patients with ASA 3/4, positive lymph node status and/or presence of LVI, administration of chemotherapy should be considered due to the high risk of poor oncological outcome. The immunohistochemical marker E-cad was not an independent predictor.

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The prognostic value of E‐cadherin, α‐, β‐ and γ‐catenin in bladder cancer patients who underwent radical cystectomy

Cited by 23 publications

References 22 publications

Reduced expression of catenin subtypes is a potential indicator of unfavorable prognosis in esophageal squamous cell carcinoma

Reduced expression of catenin subtypes is a potential indicator of unfavorable prognosis in esophageal squamous cell carcinoma

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

Outcome of Patients with Pathological Tumor Stage T3 Urothelial Carcinoma of the Bladder following Radical Cystectomy in a Single-Center Series with 116 Patients

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