The Interplay of Proteins Encoded by CDKN1A, CDKN1B, CDKN2A and TP53 in the Prognosis of Breast Cancer

Valentina Robila1 *, Bryce S Hatfield1 , Nitai Mukhopadhyay2 and Michael O Idowu1

Department of Pathology, VCU School of Medicine, USADepartment of Biostatistics, VCU School of Medicine, USA

^*Correspondance to: Valentina Robila 

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Abstract:

The use of palbociclib has increased the spotlight on cell cycle regulators, especially on the proteins encoded by CDKN2A (p16), CDKN1A (p21), CDKN1B (p27), cyclin D1 and TP53 (p53). Cell cycle regulators and cyclin-dependent kinases show significant promise as new breast cancer biomarkers. Expression patterns of small sets of proteins in breast carcinoma were reported, and their overall role in breast cancer progression was investigated, with mixed results. The goal of our study was to simultaneously evaluate multiple cell cycle regulators in breast carcinoma. The protein expression was assessed on Tissue Microarrays (TMA) and the intensity and percentage of positive tumor cells were quantified. Statistical analysis was performed to establish patterns of protein associations, as well as correlation with prognostic factors, including metastases/recurrence and overall survival. Non-triple negative carcinoma showed significantly increased expression of cyclin D1, marginally increased expression of p21, 27, and decreased expression of p16, p53. This is in contrast to triple negative carcinoma which expressed high levels of p16 and p53. Statistically significant dual proteins associations were demonstrated, including direct correlations of expression of cyclin D1 with p21 or 27, and indirect correlations with p16 and p53. Cyclin D1 (p=0.0001) and p21 (p=0.0049) expression imparted a favorable outcome on development of metastases and/or survival, while p16 (p=0.0048) had a negative impact, particularly on non-triple negative carcinoma. The remainder of the tested proteins showed no prognostic significance. Given these proteins expression patterns, associations and prognostic impact, the results render cyclin D1, p21 and p16 as potential biomarkers for risk stratification in breast carcinoma.

Keywords:

Invasive breast carcinoma; Cyclin dependent kinases; p21; p16; Metastases

Cite the Article:

Robila V, Hatfield BS, Mukhopadhyay N, Idowu MO. The Interplay of Proteins Encoded by CDKN1A, CDKN1B, CDKN2A and TP53 in the Prognosis of Breast Cancer. Clin Oncol. 2019; 4: 1644 .