Análisis de la expresión de HER2/GRB7 y su asociación con variables clinicopatológicas en un grupo de mujeres con diagnóstico de cáncer de mama invasivo

Abstract

Breast cancer is a heterogeneous disease at the clinical and molecular level (Turashili & Brogi, 2017), characterized by the development of neoplasms in the mammary glandular tissue (Feng et al., 2018, Sharma et al., 2010). It can be caused by various genetic factors, hereditary, environmental and lifestyle (Shin et al., 2010; Chen et al., 2011, Morch et al. al., 2017). This disease ranks first in incidence and mortality in women a world level and in Colombia. According to Globocan data, in 2018, 3702 were reported deaths and 13,380 new cases in the country, which has been considered a health problem public (Globocan, 2018; Pardo et al., 2017). Within this disease are recognized different molecular subtypes, luminal (luminal A and luminal B), HER2-enriched, type baseline and normal-like, each with different prognostic characteristics and clinicopathological behavior (Perou et al., 2000; Sorlie et al., 2001; Sorlie et al., 2003). In practice routine clinic, immunohistochemical marker evaluation is used where assesses the expression of hormone receptors (estrogen receptor and receptor progesterone), HER2 and Ki67 (Goldhirsch et al., 2011) for the allocation of cases in subtypes of breast cancer. The frequency of these subtypes varies between different populations (DeSantis et al., 2016; Troester et al., 2018). For the population Colombiana has reported a high prevalence of luminal subtype B (Gómez et al., 2015; Serrano et al., 2016; Ossa et al., 2015). At the molecular level, our population has described a differential expression of the ERBB2 and GRB7 genes in luminal B tumors specifically in patients with a higher fraction of American indigenous ancestry (Serrano et al., 2017), These genes code for the HER2 and GRB7 proteins, which are related to proliferation, survival and cell migration processes (Loibl & Gianni, 2017; Turke et al., 2012; Luoh et al., 2019, Fernández et al., 2008), and in turn its co-expression has been reported associated with a worse disease prognosis (McCann & Slamon, 2018, Sareyeldin et al., 2019; Chu et al., 2019). In Colombia, the prognostic value of the HER2 and GRB7 coexpression is unknown, so the present work aimed to analyze the presentation of clinicopathological variables according to the expression of these proteins in Colombian women with invasive breast cancer diagnosed in the National Cancer Institute between 2013 and 2015. Our results include found that the GRB7 protein was mainly expressed in the HER2 subtypes positive (p = <0.05). Additionally, and contrary to what is reported in the literature, our Results suggest that HER2 + / GRB7 + tumors had a smaller tumor size, lower recurrence rate and longer relapse-free survival time, suggesting that the co-expression of HER2 and GRB7 does not confer worse characteristics prognosis compared to when only HER2 is expressed.