Breast Cancer and p16: Role in Proliferation, Malignant Transformation and Progression.

Dalibor V Jovanovic,Vladica M Nedeljkovic,Vesna D Stankovic,Milena B Ilic,Danijela B Milosev,Goran L Azanjac,Dragce Radovanovic,Milos Z Milosavljevic,Milena S Vuletic,Milica N Dimitrijevic Stojanovic,Slobodanka L Mitrovic

doi:10.3390/healthcare9091240

Dalibor V Jovanovic, Vladica M Nedeljkovic + Show 9 more

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https://doi.org/10.3390/healthcare9091240

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Abstract

The definition of new molecular biomarkers could provide a more reliable approach in predicting the prognosis of invasive breast cancers (IBC). The aim of this study is to analyze the expression of p16 protein in IBC, as well as its participation in malignant transformation. The study included 147 patients diagnosed with IBC. The presence of non-invasive lesions (NIL) was noted in each IBC and surrounding tissue. p16 expression was determined by reading the percentage of nuclear and/or cytoplasmic expression in epithelial cells of IBC and NIL, but also in stromal fibroblasts. Results showed that expression of p16 increases with the progression of cytological changes in the epithelium; it is significantly higher in IBC compared to NIL (p < 0.0005). Cytoplasmic p16 expression is more prevalent in IBC (76.6%), as opposed to nuclear staining, which is characteristic of most NIL (21.1%). There is a difference in p16 expression between different molecular subtypes of IBC (p = 0.025). In the group of p16 positive tumors, pronounced mononuclear infiltrates (p = 0.047) and increased expression of p16 in stromal fibroblasts (p = 0.044) were noted. In conclusion, p16 protein plays an important role in proliferation, malignant transformation, as well as in progression from NIL to IBC.

Highlights

Invasive breast cancer (IBC) is a heterogeneous group of tumors that show different biological behavior, prognosis, and response to treatment [1]
We examined the expression of p16 protein in the tissue of 147 patients with IBC in whose environment the fields of in situ lobular and ductal carcinoma (ISC), atypical hyperplasia (AH), and normal ductoacinar structures of the breast parenchyma are present
We indicate that increased p16 expression is accompanied by an increased proliferation index determined by Ki67 nuclear expression, as reported by other authors [56,57]. These results indirectly show that high p16 expression assumes a poorer prognosis of the disease [56,57]

Summary

Introduction

Invasive breast cancer (IBC) is a heterogeneous group of tumors that show different biological behavior, prognosis, and response to treatment [1]. Numerous studies have investigated the association of individual biomarkers with clinicopathological characteristics and/or treatment outcomes [2,3,4]. Despite the significance of prognostic factors, their accuracy in assessing disease outcomes and determining therapeutic strategies is limited. The definition and validation of new molecular biomarkers could provide a more reliable approach in predicting the prognosis of this disease, which would indicate the possibility of application for therapeutic purposes

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