The Association Between the Expression of ER, PR Receptors, HER2/neu, P53 Markers and AgNORs in Breast Tumors Among Yemeni Women

Abstract

This is a prospective descriptive immunohistochemical (IHC) study carried out at National Oncology Center- Al-Jumhory Teaching Hospital, Sana'a, Yemen, during the period from August 2007 to August 2009. The study aimed to identify the incidence of ER, PR, HER-2/neu and P53 in Yemeni women with breast lesions and to assess the association between these markers and mean count of Argyrophylic Nuclear Organiser Regions (AgNORs) in benign and malignant breast lesions, as well as, to identify the association between these tumor markers and clinicopathological factors. One hundred and fifty seven consecutive mastectomy or lumpectomy biopsies were obtained from female patients with breast lesions. Demographical and clinicopathological factors were obtained from patients' reports. For all patients, representative formalin-fixed paraffin embedded (FFPE) tissues were selected, from mastectomy or lumpectomy biopsies, for ER, PR, HER2, p53 IHC study and AgNORs counting. Of the157 patients, 137 were found with malignant changes and considered as cases; among whom 124(90.5%) were identified with invasive ductal cacrinomas (IDC) and 13(9.5%) were with non-invasive ductal carcinomas (Non IDC). The remaining 20 specimens were benign tumors and ascertained as controls, among which 5 were diagnosed as mastitis, 5 were fibrocystic changes and 10 were fibroadenomas. Most cases in our study were between 30 and 50 years old (54.7%) while those >50 years old were 33.6%. ER, PR, HER2 and p53 were positive expressed in 53.3%, 40.1%, 25.5% and 48.2% of the cases respectively. In control group the positive expression was 70% for ER and PR while HER2 and p53 didn't show any expression. The mean of AgNORs counts in cases and controls were 2.57±0.78 and 1.26±0.17 respectively with significant differences (p<0.0001). While PR expression offered significant differences between cases and controls (p= 0.010), the ER expression didn't show any significant differences (p=0.160). Furthermore, when the immunostaining intensity was considered (according to the +1 to +3 scoring), the mean expression of PR was more in controls than in cases (controls= 2.60 v.s malignant= 1.81) with significant difference (p=0.005), while ER expressed more in cases than controls but without significant difference (controls= 2.55 v.s malignant= 2.27; p= 0.370). There is a tendency of decrease in HER2 and p53 expression with increase expression of ER and PR receptors with significant inverse association (ER vs HER2 p <0.0001; ER vs p53 p= 0.010; PR vs HER2 p= 0.003; PR vs p53 p=0.023). No statistically significant association between the HER2 over-expression and p53 expression (p= 0.402). The positive or negative expression of ER, PR, HER and p53 didn't show association with clinicopathological factors, except the positive significant association between ER and PR expression with lymph node involvement ( p= 0.004, p= 0.022 respectively) while p53 was negatively associated with lymph nodes involvement (p= 0.034). P53 also associated positively to tumor size with borderline significant (p= 0.066). Like tumor markers; AgNORs mean counts didn't show any significant differences with clinicopathological factors except with tumor grade, where the mean of AgNORs counts increase with tumor grade (grade I=2.66 v.s grade III= 3.41; p= 0.001). With the tumor markers, the mean of AgNORs counts were high in hormonal receptors negative (ER+ve = 2.45 v.s ER-ve= 2.71 and PR+ve= 2.36 v.s PR-ve= 2.71) and p53 positive cases (p53+ve =2.81 v.s p53-ve=2.36), while with HER2 did not show any significant differences (HER2+ve =2.58 v.s HER2-ve = 2.57; p =0.997). According to this study, hormonal receptors in our population may be helpful in the treatment protocol for less than 50% of the patients and especially for those with lymph node involvement. On the other hand, p53 may play an important role as prognostic marker especially in those patients with negative lymph nodes. Silver staining for AgNORs estimation can be used as additive technique to histopathology for benign and malignant differentiation, as well as, in the prognosis. Although, the HER2 didn't revealed any association with clinicopathological factors, its analysis is important because it provides valuable prognostic and therapeutic information especially in patients with negative hormone receptors. Follow up and Genetic studies are recommended to achieve a definite conclusion.