β-Catenin Stability, Cyclin D1 and Frizzled Proteins Expression in Human Breast Cancer and Their Relation with the Prognosis

Abstract

A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Aberrant Wnt signaling pathway activation and stabilization of β-catenin protein is associated with tumorigenesis and human breast tumors. We have examined β-catenin, cyclin D1, sFRP1 and sFRP2 expressions in the breast cancer and effects of these factors on prognostic parameters in patients with breast cancer. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : One hundred and seventeen consecutive female malignant breast tumor patients were enrolled into the study. The mean age was 50.0 (±18.0) years. Immunohistochemical staining method was used to investigate the stability and location of β-catenin, expressions of sFRP1 and sFRP2 and cyclin D1 proteins. R Re es su ul lt ts s: : Percentage expression of β-catenin, siklin D1, sFRP1 and sFRP2 were 60.0 ± 55.0, 40.0 ± 64.0, 15.0±48.0 and 25.0 ± 53.0, respectively. Menopausal status, progesterone receptor positivity, lymph node involvement and TNM staging did not show any statistically significant relation with the expression of β-catenin, cyclin D1, sFRP1 or sFRP2. However, significantly higher percentages of expression of cyclin D1 were determined in patients showing estrogen receptor positivity and cerbB-2 over-expression (p= 0.008). Additionally β-catenin expression was significantly higher only in the p53-positive group (p= 0.03). None of the parameters used in this study showed a significant effect on clinicopathological prognostic parameters. C Co on nc cl lu us si io on n: : These findings suggested that expression levels and staining results of β-catenin, cyclinD1, sFRP1 and sFRP2 in tumor cells were independent from histological grade, lymph node involvement, and TNM stage. We concluded that β-catenin accumulation, cyclin D1, sFRP1 and sFRP2 expressions were not affected by the Wnt signaling pathway. K Ke ey y W Wo or rd ds s: : Breast neoplasm; β-catenin; cyclin D1; secreted frizzled related proteins Ö ÖZ ZE ET T A Am ma aç ç: : Wnt sinyal yolağının aberan aktivasyonu ve β-katenin proteininin stabilizasyonu tümör gelişimi ve insan meme tümörleri ile ilişkilidir. Bu çalışmada, meme kanserinde β-katenin, siklin D1, sFRP1 ve sFRP2 ekspresyonlarını ve bu faktörlerin hastaların prognostik parametreleri üzerine etkilerini incelemeyi amaçladık. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Ortalama yaşı 50 ± 18 olan ardışık 117 meme kanserli kadın olgu çalışmaya alındı. İmmünositokimyasal yöntemle β-katenin stabilitesi, sFRP1, sFRP2 ve siklin D1 proteinlerinin ekspresyonları değerlendirildi. B Bu ul lg gu ul la ar r: : β-katenin, siklin D1, sFRP1 ve sFRP2'nin ekspresyonları sırasıyla %60.0 (±55.0), %40.0 (±64.0), %15.0 (±48.0) ve %25.0 (±53.0) idi. Menopozal durum, progesteron reseptörü, lenf nodu tutulumu, TNM evresi ile β-katenin, siklin D1, sFRP1 veya sFRP2 ekspresyonu arasında istatistiksel olarak anlamlı bir ilişki bulunmadı. Bununla birlikte olgularda östrojen pozitifliği ve cerbB-2 pozitifliği ile siklin D1 arasında istatistiksel olarak anlamlı ilişki varlığı izlendi (p= 0.008). β-...

The Wnt Pathway Components are Upregulated in Different Molecular Subtypes of Invasive Ductal Carcinoma Patients of Breast

“…On the other hand, contradictory to our results, He et al reported significant correlation of β-catenin and cyclin D1 over expression with the differentiation grade, clinical stage and lymph node status of breast cancer patients [19]. Apart from this, Zengel, et al failed to find any correlation of clinic pathological parameters with β-catenin or cyclin D1 in breast cancer patients [20].…”

“…Cyclin D1 expression was not of prognostic value in early stage breast cancer patients [30]. Contradictorily, higher expression of cyclin D1 was associated with better prognosis in breast cancer patients with Her2 over expression [20,31]. In conclusion, the over-expression of the Wnt pathway components is likely to have a role in early stages of breast cancer development leading to the cancer progression.…”

“…Moreover, β-catenin gene has been identified to correlate with the ER expression in breast cancer cell lines and patient derived metastatic breast cancer samples [23]. On the other hand, Zengel, et al did not observe any correlation between β-catenin and ER/PR or Her2 expression [20].…”

“…The present study too observed significant association of Fzd7, β-catenin and cyclin D1 with ER + and PR + status indicating that ER pathway activates Fzd7 and β-catenin resulting in activation of cyclin D1 and thereby Wnt signaling pathway. Contradictorily, some studies reported higher cyclin D1 expressions to be associated with ER -, PRand Her2 -breast tumours [20,23]. Moreover, β-catenin gene has been identified to correlate with the ER expression in breast cancer cell lines and patient derived metastatic breast cancer samples [23].…”