Investigation of CCR7 Marker Expression Using Immunohistochemical Method and Its Association with Clinicopathologic Properties in Patients with Breast Cancer

Abstract

Background: Breast cancer is one of the most common cancers among women in the world, especially in Iran. There are large numbers of molecular and genomic factors causing breast cancer as well as many markers associated with tumor invasion.
Chemokines are small proteins that primarily regulate leukocyte trafficking in the homeostatic conditions and specific immune responses. Chemokine receptor 7 (CCR7) belongs a class A subtype 7-span transmembrane G-protein coupled receptor. CCR7 plays a role in the migration of tumor cells such as immune cells into lymphoid organs through binding to its only two ligands CCL19/CCL21.
High expression of this marker has been observed in breast cancer. However, there have been limited and contradictory data in studies conducted on the relationship between the increasing expression of this marker with various clinical and pathological factors.
Materials and Methods: This case-control practical study was carried out on total mastectomy samples from 70 patients with breast cancer and tumor-adjacent normal tissue using immunohistochemistry technique to assess the expression of CCR7 marker. The relationship among the marker expression with different clinical and pathological tumor factors such as age, tumor size, microscopic grade, neurovascular invasion, lymph node metastasis and tumor stage were evaluated in all patients. Since the both groups were matched for age, so McNemar test, Chi-square test and Fisher's exact test were used to compare the expression of CCR7 marker in the case and control groups. Conditional logistic regression was employed to compare the effects of other variables regarding the age harmonization.
Results: CCR7 expression was observed in 63 (91.4%) out of 70 studied patients and in tumor-adjacent normal tissue of 55 patients (78.6%), while the marker expression intensity in normal tissue was lower than tumoral tissue (P<0.032)
There was a significant relationship among the expression of CCR7 marker with disease stage (P<0.001), grade (P<0.035), lymph node metastasis (P<0.003), perineural invasion (P<0.037) and vascular invasion (P<0.01), but no significant relationship was found among CCR7 expression with other tumor clinicopathologic parameters such as age (P>0.19) and tumor size (P>0.105).
Conclusion: Increased expression of CCR7 has a significant relationship with disease stage, grade, lymph node metastasis and neurovascular invasion of breast cancer but has no relationship with age of patients and tumor size. Therefore, this biomarker can be utilized as a predictive factor for tumor metastasis and survival of patients.