β-catenin expression as a prognostic indicator in cervical adenocarcinoma

Imura, Johji; Ichikawa, Kazuhito; Takeda, Jinryo; Fujimori, Takahiro

doi:10.3892/ijmm.8.4.353

Cited by 24 publications

(22 citation statements)

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“…b-catenin is an important member of both the WNT-signaling pathway and the cell-cell adhesion pathway. However, immunohistochemical analysis revealed no relation between b-catenin and lymph node metastases, which is in agreement with other studies (31,40) and indicates that the canonical Wnt/ b-catenin pathway (containing b-catenin, Wnt1, APC) is not involved in mediating the invasive potential in cervical cancer. In normal cervical epithelium, b-catenin is involved in E-cadherin mediated cell-cell adhesion, by binding to the cytoplasmic domain of E-cadherin.…”

Section: Discussionsupporting

confidence: 81%

Involvement of the TGF-β and β-Catenin Pathways in Pelvic Lymph Node Metastasis in Early-Stage Cervical Cancer

Noordhuis

Fehrmann²,

Wisman

et al. 2011

Clinical Cancer Research

114

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Purpose: Presence of pelvic lymph node metastases is the main prognostic factor in early-stage cervical cancer patients, primarily treated with surgery. Aim of this study was to identify cellular tumor pathways associated with pelvic lymph node metastasis in early-stage cervical cancer.Experimental Design: Gene expression profiles (Affymetrix U133 plus 2.0) of 20 patients with negative (N 0 ) and 19 with positive lymph nodes (N þ ), were compared with gene sets that represent all 285 presently available pathway signatures. Validation immunostaining of tumors of 274 consecutive early-stage cervical cancer patients was performed for representatives of the identified pathways.Results: Analysis of 285 pathways resulted in identification of five pathways (TGF-b, NFAT, ALK, BAD, and PAR1) that were dysregulated in the N 0 , and two pathways (b-catenin and Glycosphingolipid Biosynthesis Neo Lactoseries) in the N þ group. Class comparison analysis revealed that five of 149 genes that were most significantly differentially expressed between N 0 and N þ tumors (P < 0.001) were involved in b-catenin signaling (TCF4, CTNNAL1, CTNND1/p120, DKK3, and WNT5a). Immunohistochemical validation of two well-known cellular tumor pathways (TGF-b and b-catenin) confirmed that the TGF-b pathway (positivity of Smad4) was related to N 0 (OR: 0.20, 95% CI: 0.06-0.66) and the b-catenin pathway (p120 positivity) to N þ (OR: 1.79, 95%CI: 1.05-3.05).Conclusions: Our study provides new, validated insights in the molecular mechanism of lymph node metastasis in cervical cancer. Pathway analysis of the microarray expression profile suggested that the TGF-b and p120-associated noncanonical b-catenin pathways are important in pelvic lymph node metastasis in early-stage cervical cancer.

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Section: Discussionsupporting

confidence: 81%

Involvement of the TGF-β and β-Catenin Pathways in Pelvic Lymph Node Metastasis in Early-Stage Cervical Cancer

Noordhuis

Fehrmann²,

Wisman

et al. 2011

Clinical Cancer Research

114

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“…The diffuse expression of p16INK4a in this group of lesions most probably links endocervical adenocarcinoma to HR-HPV infection, possibly through inactivation of the pRB protein by E7 HPV protein [26,27].…”

Section: Discussionmentioning

confidence: 96%

“…Fewer studies have recently focused also on the E-cadherin-catenin complex expression in endocervical adenocarcinomas [26][27][28], and all have showed decreased expression of the E-cadherin-catenin complex with atypical patterns of α-and β-catenin expression.…”

Section: Introductionmentioning

confidence: 99%

Adhesion molecules and p16 expression in endocervical adenocarcinoma

et al. 2009

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An immunohistochemical (IHC) study has been conducted on 34 cases of untreated endocervical adenocarcinomas collected among three institutions (Ospedale S. Andrea, Rome; Istituto Nazionale Tumori "Fondazione G. Pascale", Naples; and Clinica Malzoni, Avellino). The E-cadherin and alpha- and beta-catenin complex status has been investigated along with p16INK4a in all studied cases with the aim to study whether the pattern of expression of the cadherin-catenin complex could be causally related to the expression of P16INK4a protein. Results were evaluated for statistical significance by a non-parametric test (Kruskal-Wallis). Endocervical adenocarcinomas as a group were uniformly expressing p16INK4a except for two cases, and all lesions displayed downregulation of the cadherin-catenin complex, without demonstrating statistically significant differences among the different histotypes. The lack of nuclear accumulation of beta-catenin found in this group of lesions probably implies that no alteration of the beta-catenin/Wnt metabolic pathway is present in endocervical adenocarcinoma, as opposed to what is found in the literature for squamous carcinoma of the cervix. The diffuse expression of p16INK4a protein in this group of neoplasms stresses the important role of high-risk human papillomavirus infection in neoplastic causation possibly via the viral E7-mediated inactivation of pRB tumor-suppressor protein and also underlines the useful role of p16INK4a immunostaining in the diagnostic algorithm of endocervical adenocarcinomas. In consideration of these findings, investigation of downstream beta-catenin genes c-myc and cyclin D1 is sought as possibly contributive in the molecular pathogenesis of endocervical adenocarcinoma.

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“…and functions as an adhesion molecule. Reduced expression of membranous h-catenin has been found to be associated with worse outcome in a variety of malignancies including ovarian (19), non -small cell lung cancer (20,21), melanoma (22), gastric (22), cervical (23), breast (24), bladder (25), and nasopharyngeal carcinoma (26). To the contrary, nuclear (signaling) h-catenin has been correlated to poor outcome in colorectal (11), hepatocellular (27), esophageal (28), hepatoblastoma (29), thyroid (30), and breast (31) carcinomas.…”

Section: Discussionmentioning

confidence: 99%

β-Catenin Functions Mainly as an Adhesion Molecule in Patients with Squamous Cell Cancer of the Head and Neck

Yang

Weinberger

Provost³

et al. 2005

Clinical Cancer Research

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Background: h-catenin, depending on subcellular localization, plays a dual role in carcinogenesis: as a signaling factor (in the nucleus) and as an adhesion molecule (in cell membrane). In this study, we sought to determine the role of h-catenin in head and neck carcinogenesis. Methods: First, we studied the incidence of mutations of h-catenin in a cohort of 60 head and neck squamous cell cancers (HNSCC).We subsequently evaluated the protein expression levels of h-catenin in a cohort of oropharyngeal squamous cell cancer tissue microarray using a novel in situ method of quantitative protein analysis and correlated those with cyclin D1levels and clinical and pathologic data. Results: The mean follow-up time for survivors was 45 months and for all patients was 35 months.We found no mutations in the cohort of 60 HNSCC. h-catenin displayed primarily membranous expression pattern. Patients with high tumor-node-metastasis stage were more likely to have high expression of h-catenin (P = 0.040). Patients with low h-catenin expression had a local recurrence rate of 79% compared with 29% for patients with high h-catenin tumors (P = 0.0021). Univariate Cox regression revealed a hazard ratio for low h-catenin tumors of 3.6 (P = 0.004). Kaplan-Meier analysis showed that patients with low h-catenin expressing tumors trended toward worse 5-year disease-free survival (P = 0.06). In multivariate analysis, only h-catenin expression status was an independent prognostic factor (P = 0.044) for local recurrence. Tumors with high h-catenin had low cyclin D1and vice versa (P = 0.007). Conclusions: The absence of activating h-catenin mutations combined with the inverse correlation between h-catenin levels with cyclin D1 levels and outcome suggest that h-catenin mainly functions as an adhesion and not signaling molecule in HNSCC.

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β-catenin expression as a prognostic indicator in cervical adenocarcinoma

Cited by 24 publications

References 0 publications

Involvement of the TGF-β and β-Catenin Pathways in Pelvic Lymph Node Metastasis in Early-Stage Cervical Cancer

Involvement of the TGF-β and β-Catenin Pathways in Pelvic Lymph Node Metastasis in Early-Stage Cervical Cancer

Adhesion molecules and p16 expression in endocervical adenocarcinoma

β-Catenin Functions Mainly as an Adhesion Molecule in Patients with Squamous Cell Cancer of the Head and Neck

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