Association of Fascin and matrix metalloproteinase-9 expression with poor prognostic parameters in breast carcinoma of Egyptian women

Abstract

Background: The effects of fascin on cell invasiveness involve changes in cell motility and matrix metalloproteinase-9 (MMP-9) activity. Previous studies on the prognostic value of fascin and MMP-9 in breast carcinoma revealed conflicting results. To date, no immunohistochemical studies have been performed to assess the possible association between them in breast carcinoma. This study is designed to correlate their expression with prognostic parameters in breast carcinoma and assess the relationship between them.

Methods: Immunohistochemical expression of fascin and MMP-9 was evaluated semi quantitatively in 67 cases of breast carcinoma regarding the percentage of positive cells. Chi square test and Fisher's exact test were used to examine the relationship between categorical variables. Kappa statistics was used to compute the measure of agreement between two investigational methods.

Results: Fascin and MMP-9 expressions were detected in 43.28% and 50.75% of breast carcinomas (respectively). Regarding the normal breast tissue, fascin expression was observed in myoepithelial cells and luminal cells of few ducts and acini. However, normal tissue showed negative MMP-9 expression. A significant relationship was observed between fascin and MMP-9 expression and lymph node metastases (p = 0.001 and 0.002 respectively), advanced tumor stage (p = 0.004 and 0.005 respectively), estrogen receptor negative (p = 0.002 and 0.005 respectively), progesterone receptor negative (p = 0.001 and 0.003 respectively) hormonal status and molecular subtypes (p = 0.0007 and 0.014 respectively). A significant strong agreement was detected between fascin and MMP-9 expression (p = 0.0001). More intense immunostaining of fascin and MMP-9 was observed at the invasive fronts compared with other areas of the tumor. Moreover, a significant moderate agreement between fascin and MMP-9 was found regarding the site of predominant intensity.

Conclusion: Fascin and MMP-9 proteins are associated with parameters of poor prognosis in breast cancer. The significant strong agreement between the two markers supports the role of fascin in cell invasiveness by activating matrix proteases besides increasing cell motility. Both proteins may represent potential therapeutic targets for patients with breast cancer especially those with hormone receptor-negative status.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1421167695121127.

Figure 1

Fascin and MMP-9 expressions in normal breast tissue and invasive ductal carcinomas. a: Moderate fascin expression in the myoepithelial cells and luminal cells of few normal acini (IHC × 400). b: Positive cytoplasmic fascin expression in malignant cells (IHC × 400). c: Negative MMP-9 expression in normal breast tissue (IHC × 400). d: Positive cytoplasmic MMP-9 expression of malignant cells with weak expression of stromal cells (IHC × 400).

Figure 2

Fascin and MMP-9 expression in invasive ductal carcinomas with adjacent in situ component. (a): Positive cytoplasmic fascin expression in the myoepithelial cells of the in situ component (IHC × 200). (b): Positive cytoplasmic fascin expression in the in situ carcinoma lesions as well as the adjacent invasive carcinoma (IHC × 200). (c): Positive cytoplasmic MMP-9 expression in the in situ carcinoma lesions (IHC × 200). (d): Positive cytoplasmic MMP-9 expression in invasive carcinoma and negative expression in the in situ carcinoma lesions (IHC × 200).

Figure 3

Relationship between fascin expression and poor prognostic parameters in breast carcinoma.

Figure 4

Relationship between MMP-9 expression and poor prognostic parameters in breast carcinoma.

Figure 5

Invasive ductal breast carcinomas. a: Enhanced fascin expression at the leading edge of the tumor (IHC × 100). b: The same field with higher magnification power showing positive cytoplasmic fascin expression of malignant cells and endothelial cells (IHC × 200). c: Enhanced MMP-9 expression at the tumor–host border (IHC × 100). d: The same field with higher magnification power showing positive cytoplasmic MMP-9 expression of malignant cells (IHC × 200).