Immunohistochemistry for Thymidine Kinase-1 (TK1): A Potential Tool for the Prognostic Stratification of Breast Cancer Patients.

Giuseppe Nicolò Fanelli,Andrea Fontana,Cristian Scatena,Mario Miccoli,Antonio Giuseppe Naccarato,Katia De Ieso,Paola Ferrari,Paola Cinacchi,Rosa Scarpitta,Anna Szumera-Ciećkiewicz,Beatrice Fuochi

doi:10.3390/jcm10225416

Abstract

Breast cancer (BC) is the most frequent non-cutaneous malignancy in women. Histological grade, expression of estrogen and progesterone receptors (ER and PgR), overexpression/amplification of the human epidermal growth factor receptor 2 (HER2) oncogene, and proliferative activity measured with ki-67 provide important information on the biological features of BC and guide treatment choices. However, a biomarker that allows a more accurate prognostic stratification is still lacking. Thymidine kinase-1 (TK1), a ubiquitous enzyme involved in the pyrimidine nucleotide recovery pathway, is a cell-proliferation marker with potential prognostic and predictive impacts in BC. Eighty (80) cases of invasive BC with a long-term follow-up were retrospectively selected, and clinicopathological data were collected for each patient. TK1 tissue expression was evaluated immunohistochemically. Data suggested that TK1 expression levels are positively correlated with ER and PgR expression, and negatively correlated with HER2 status and the impact on patients’ distant recurrence-free survival (DRFS): in detail, among patients undergoing adjuvant chemotherapy, lower TK1 levels are correlated with better DRFS. Therefore, these results contribute to furthering the knowledge of TK1, suggesting a possible and important role of this enzyme as a biomarker in the stratification of BC patients.

Highlights

Breast cancer (BC) represents the most frequent non-cutaneous malignant tumor in women, accounting for approximately 30% of all cancer diagnoses [1]
In the last 20 years, gene expression studies have highlighted a considerable heterogeneity within BC, leading to the identification of subtypes with differences in biological characteristics and clinical course [3,4]; some of these, such as triple-negative cancers (TNBC), have a poor prognosis and limited therapeutic possibilities [5]
PgR), overexpression of the human epidermal growth factor receptor 2 (HER2) oncogene, and proliferative activity, measured by ki-67, represent crucial parameters that provide important information on the biology of BC, which guide the choice of treatment

Summary

Introduction

Breast cancer (BC) represents the most frequent non-cutaneous malignant tumor in women, accounting for approximately 30% of all cancer diagnoses [1]. BC represents the second leading cause of cancer death in females worldwide, after lung cancer [1]. In the last 20 years, gene expression studies have highlighted a considerable heterogeneity within BC, leading to the identification of subtypes with differences in biological characteristics and clinical course [3,4]; some of these, such as triple-negative cancers (TNBC), have a poor prognosis and limited therapeutic possibilities [5]. Histological grade, expression of estrogen and progesterone receptors Despite all the efforts to control the disease, a considerable number of patients experience relapse and metastasis, resulting in a very poor prognosis [6]. Studied over the past 20 years, thymidine kinase-1 (TK1) is a ubiquitous enzyme that plays a key role in the pyrimidine nucleotide recovery pathway for DNA damage synthesis and repair [7,8]

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