P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer

Abstract

P-cadherin is a calcium-dependent cell-cell adhesion glycoprotein. P-cadherin expression is restricted to the myoepithelial cells in normal breast tissue, and aberrant staining has also been described in invasive tumors. Several small studies have reported P-cadherin as a marker of poor outcome in breast cancer patients but its prognostic significance in relation to other variables has not been established in a large series of breast cancers. A tissue microarray was constructed from 3992 cases of invasive breast carcinoma, and P-cadherin expression was evaluated using immunohistochemistry. Median follow-up was 12.5 years. The immunohistochemistry-based definitions of cancer subtypes were luminal, and basal (ERÀ/PRÀ/HER2À/CK5/6 þ or EGFR þ ). Clinical covariate and biomarker associations were assessed using contingency tables, and Pearson's v 2 or Fisher's exact test. Survival associations were assessed using Kaplan-Meier plots, logrank and Breslow tests, and Cox proportional hazards regression analysis. P-cadherin was expressed in 34.8% (1290/3710, 50% cut point) of cases. P-cadherin staining was strongly associated with HER2 þ and basal carcinoma subtypes (Po0.0005). P-cadherin-positive patients showed significantly poorer short-term (0-10 years) overall survival, disease-specific survival, distant relapse-free interval, and locoregional relapse-free interval in univariable models (Po0.05). In multivariable Cox models containing standard clinical covariates and cancer subtypes, P-cadherin did not show independent prognostic value. P-cadherin expression was positively associated with histological grade, chemotherapy, EGFR, CK5/6, p53, and HER2 expression (Po0.002), and negatively associated with age at diagnosis, ER, PR, and Bcl-2 expression (Po0.0005). This study shows the value of P-cadherin as a marker of poor prognosis. The large sample size of this series clarifies contradictory findings of many smaller studies. P-cadherin positivity is associated with high-grade tumor subtypes and well-established markers of poor prognosis, and may represent a promising antibody therapeutic target.

A Clinical Database of Breast Cancer Patients Reveals Distinctive Clinico-pathological Characteristics: a Study From Central China

“…MRM is decreasing and have been a non-mainstream operation pattern in developed countries (Ko et al, 2012;Piscitelli et al, 2012). While, our study showed MRM was still the major surgical treatment accounting for 71.8%, similar to another study from China (79.7%), which is much higher than developed counties/areas (Ko et al, 2012;Turashvili et al, 2011;Wei et al, 2010). As a safe treatment procedure, BCS has been expanded for more than 20 years since the National Institutes of Health Consensus Development Conference Statement was released advising breast conservation (Abrams et al, 1995).…”

“…One notable fact is the relatively younger age of BC for Chinese females. The median age was 50 years in this study, which was similar to Shanghai (50 years) (Fan et al, 2009), Korean (49 years) (Ko et al, 2012), lower than Western developed countries (the United States: 62 years (Anderson et al, 2006); Canada: 60 years (Turashvili et al, 2011); German: 59 years (Fritz et al, 2010); Belgium: 58 years (Brouckaert et al, 2013) ). Percentage of BC < 50 years in America was 27.0% (Desantis et al, 2013), much lower than this study (47.0%).…”

“…RM, MRM, BCS, and SM were the 4 common types of BC surgery in China, (Yu et al, 2007;Zhang et al, 2013) accounting for 18.0% (454/2,525), 71.8% (1,812/2,525), 5.2% (131/2,525) and 2.6% (66/2,525) of the cases, respectively, in our study. Because BCS could maintain the shape and function of breast, it has been popular for several decades and become the most common surgical procedure in developed areas such as Korea (60.6%), (Ko et al, 2012) Hong Kong (43.5%) (Kwong et al, 2011) and Canada (44.8%) (Turashvili et al, 2011). However, this treatment is not well-received in China.…”

P-cadherin role in normal breast development and cancer

“…However, P-cadherin was described as being overexpressed in 20% to 40% of invasive breast carcinomas, as well as in 25% of ductal carcinomas in situ (DCIS) (Paredes et al, 2007a, Paredes et al, 2007b, Paredes et al, 2002. Most important, several studies have reported P-cadherin as a marker of poor prognosis in breast cancer, since P-cadherin-positive carcinomas were significantly associated with short-term overall and disease-specific survival, as well as with distant and loco-regional relapse-free interval (Gamallo et al, 2001, Peralta Soler et al, 1999, Turashvili et al, 2011. P-cadherin expression has also been positively associated with high histological grade tumours, as well as with well-established markers of poor prognosis, like Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5 (CK5), vimentin, p53, and HER2 expression and negatively associated with age at diagnosis, hormonal receptors (ER and PgR), and Bcl-2 expression.…”

Application of Immunohistochemistry in Breast Pathology: A Review and Update

“…Other MEC markers, such as SMA, p-cadherin, Wilms tumor 1 (WT1), S100, and high-molecular-weight cytokeratin (HMWCK) or basal-type cytokeratin (CK) (CK5/6, CK14, CK17, CK903) are less commonly used because of marked cross-reactivity with myofibroblasts and vascular SMA, [4][5][6][7][8][9]19,20 frequent reactivity in tumor cells (HMWCK or basal-type CK, S100, p-cadherin), [4][5][6][7][8]19,[32][33][34] or low sensitivity (WT1 and S100). 33 Podoplanin (D2-40), a marker labeling lymphatic endothelium, was observed to be variably expressed in breast MECs surrounding benign ducts and lobules as well as in CISs.…”