Abstract
In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. In this report, we analyzed the protein expression in patients with BCa and in healthy women. Links with some clinic-pathological characteristic were also assessed. Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed using χ2 or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means. We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison with healthy tissue. A significant association between protein expression with smoking, alcoholism and hormonal contraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor (PR) positive association in BCa. We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments. One therapeutic approach may thus be to block CYP3A4 function.
Highlights
In 2011, World Health Organization (WHO) estimated that the leading cause of worldwide death during 2008 was cancer with 7.6 million cases mainly lung, stomach, liver, colon and breast cancer (BCa) (World Health Organization, 2012)
Materials and Methods: Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011
We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments
Summary
In 2011, World Health Organization (WHO) estimated that the leading cause of worldwide death during 2008 was cancer with 7.6 million cases mainly lung, stomach, liver, colon and breast cancer (BCa) (World Health Organization, 2012). BCa etiology has been attributed to factors such as advanced age, reproductive, personal and family history, estrogen metabolism, geographic area and diet (Lopez-Carrillo, 2003) These observations suggest that environmental factors, diet, physical inactivity and obesity, as well as the increase in the consumption of alcohol and saturated fat and sugar diet are involved in BCa progression (Blacam et al, 2012; Canchola et al, 2012; Nelson et al, 2012; Xing et al, 2014). For automated morphometric analysis the percentage of positive cells (brown color) was determined with a computerized image analyzer KS-3003.0 (Carl Zeiss, Jena, Germany). This equipment automatically detects positive cells per field by determining their percentage.
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