RESUMO
This study was performed to investigate possible relationships between the manifestation of stromal cells [fibroblasts and/or myofibroblasts] by focusing on expression of their matrix metalloproteinase 9 [MMP9] and possible angiogenesis based on CD31 and CD34 antigen expression during the various steps of hyperplastic changes to precancerous state and invasive breast cancer. Our study included 50 females with invasive ductal carcinoma. Samples were obtained by mastectomy or biopsy and were immunohistochemically stained for the MMP9, CD31, and CD34 antibody. microvessel count [MVC] was also carried out on samples. Statistical analysis of the data was performed using ANOVA and Student's t-test [P < 0.05]. Findings were compared with our "Breast Cancer Data Bank" for reevaluation of their clinical staging. Positive significant correlations were observed between expression of MMP9 and invasive ductal carcinoma in situ [DCIS] and fibrocystic disease +/- ductal intraepithelial neoplasia [FCD +/- DIN] areas [P=0.001]. MMP9 expression in invasive areas was more strongly positive than precancerous areas. Statistically significant correlations were observed between MMP9 expression and CD31 in grade II in invasive areas. MVC was evaluated by CD31 antibody. It was found to be inversely related to increased MVC from invasive areas, DCIS, DIN, and normal areas [P < 0.001]. No significant difference was observed in MVC based on age, tumor size or steroid receptors in stroma of an invasive cancer, DCIS, and FCD +/- DIN. MMP9 expression in invasive areas was more strongly positive than precancerous areas, and negative in normal areas. Angiogenesis can be observed before any significant changes in preinvasive breast lesions. The elevated content of microvessel count of the tumor may be an indicator for worse prognostic factor. The progression from epithelial hyperplasia toward DCIS, and then, invasive carcinoma seems too complex to be assumed a linear progression
RESUMO
This study seeks to determine the relationships between manifestation of myofibroblast in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. Handred cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin [SMA], ER/PR, HER2, anti-CD34 antibody and microvessel count [MVC]. Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease +/- ductal intraepithelial neoplasia [FCD +/- DIN], and normal tissue. There was a significant difference in stromal myofibroblast between all areas except for the stroma of DCIS and FCD +/- DIN [P < 0.001]. We observed positive significant correlations between stromal myofibroblast, HER2 expression, and the numbers of involved lymph nodes in invasive cancer, DCIS, and FCD +/- DIN [P < 0.001]. More myofibroblast were present in grade III cases, with the least frequent observed among grade I cases in the stroma of those with invasive disease, DCIS, and FCD +/- DIN [P < 0.001]. MVC was inversely related to stromal myofibroblast in invasive cancer [P < 0.001] and DCIS [P < 0.001], whereas there was a positive correlation in the stroma of FCD +/- DIN [P = 0.002] and normal areas [P = 0.054]. There was a significant difference in MVC observed in all areas except for DCIS and FCD +/- DIN [P < 0.001]. We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS [P < 0.001]. Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD +/- DIN [P < 0.001]. Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblast in stroma of tumor; probably may be a worse prognostic factor and the steps from atypical epithelial hyperplasia to DCIS and then to the invasive carcinoma do not appear to be always part of a linear progression