P-cadherin expression and basal-like subtype in breast cancers

Abstract

Breast cancer is considered as one of the multifactorial diseases. The aim of the current study is to investigate the association between P-cadherin and molecular subtypes of breast cancer, especially the basal-like subtype. Two hundred and thirteen breast-invasive ductal carcinomas were involved in this study. The expressions of P-cadherin were detected via immunohistochemistry. The 213 cases were divided into luminal A, luminal B, HER2 overexpression subtype, and normal breast-like and basal-like subtypes according to the standard of molecular breast cancer subtypes. In addition, the expressions of CK5/6 and CK14 were detected to distinguish between the normal breast-like and the basal-like subtypes. P-cadherin expression was found in 91 cases of 213 breast-invasive ductal carcinomas, with a positive rate of 42.7%. P-cadherin correlated negatively with estrogen receptor (ER) (p=0.001) and progesterone receptor (p=0.001), whereas it positively correlated with histologic grade (p=0.003), NPI (p=0.005), p53 (p=0.038), and Ki67 (p=0.022). P-cadherin expression showed a strong correlation with recurrence and distant metastasis (p=0.009), and invasion of the vascular and soft tissues (p=0.004). Moreover, P-cadherin expression existed in the basal-like and non-basal-like subtypes. During prognosis, P-cadherin expression was associated with decreased disease-free survival in patients (p=0.009) and overall survival (OS) (p=0.005). In addition, multivariate analysis showed that tumor grade (p=0.021), ER (p=0.015), clinical stage (p=0.001), and P-cadherin (p=0.033) were significant predictors of OS. The current data suggest that P-cadherin may be used to distinguish the basal-like subtype and to predict the outcome in view of the relationship with DFS and OS. Furthermore, P-cadherin expression may be useful in making treatment decisions.

Induction of entosis by epithelial cadherin expression

“…Many human breast tumors express the epithelial cadherin proteins E-cadherin [19] or P-cadherin [20]. However, we found that many human breast tumor cell lines lacked epithelial cadherin expression ( Figure 1B and Supplementary information, Figure S1A) and were deficient in entosis ( Figure 1A).…”

“…However, many breast tumors including the most invasive ductal carcinomas and metastatic tumors retain E-cadherin expression, and E-cadherin may promote tumor progression by supporting cell survival, collective modes of invasion, or the outgrowth of metastatic tumors that may be promoted by an epithelial rather than mesenchymal phenotype [19,[33][34][35][36][37][38][39]. Like E-cadherin, P-cadherin is also expressed in some breast cancers and is a poor prognostic indicator [20]. We have shown that in addition to causing cell death that limits transformed growth, entosis can also (1) induce aneuploidy by disrupting cytokinesis [7], (2) support cell survival under nutrient-limiting conditions [10], and (3) promote cell competition that could contribute to clonal progression (see the companion paper by Sun et al [12]), suggesting that this cannibalistic cell behavior could conceivably promote tumor progression in the long term, and could potentially contribute to some of the tumor-promoting activities of epithelial cadherins.…”

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review)

“…The current molecular classifications of breast cancer molecular subtypes are generally based on the gene expression profiles according to i) luminal cell-related markers, such as cytokeratins (CKs); ii) hormone receptors, such as estrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR); iii) growth factor receptors, such as human epidermal growth factor receptor (HER); iv) anti-apoptosis markers, such as Bcl-2 and p53; v) cell proliferation indicators, such as Ki-67 and survivin; vi) cell invasion-related factors, such as matrix metalloproteinases (MMPs) and integrins; vii) signal transduction pathway members, such as the PI3K̸AKT pathway members phosphatidylinositol-3-kinase (PI3K) and AKT; viii) cell cycle control members, such as cyclins and cyclin-dependent kinases (CDKs); ix) epithelial-to-mesenchymal transition-indicating factors and regulating factors, such as cadherins and zinc-finger transcription factors Snail, Slug, Zeb1 and Twist; x) metastatic control factors; and xi) blood vessel-forming control factors (8)(9)(10). This spectrum also includes stem cell markers, tumor cell and microenvironment interacting factors and other small regulatory molecules, such as microRNAs or other non-coding RNAs.…”

Aberrant P-cadherin expression is associated to aggressive feline mammary carcinomas

“…However, this result must be regarded with caution, since the wide confidence interval (CI) reveals a low precision of the estimate. Although in human breast cancer P-cadherin overexpression has been associated with decreased survival and relapse-free intervals [ 36 , 64 ], other studies failed to find a significant association between P-cadherin and lymph node metastases at the time of diagnosis [ 11 , 21 , 27 ]; however, Gamallo et al . [ 26 ] found an association between P-cadherin expression and lymph node-positive breast tumours.…”