The clinicopathological significance of neurogenesis in breast cancer

BACKGROUND: Recent reports support a novel biological phenomenon about cancer related neurogenesis. However, little is known about the clinicopathological significance of neurogenesis in breast cancer. METHODS: A total of 196 cases, including 20 of normal tissue, 14 of fibroadenoma, 18 of ductal carcinoma in situ (DCIS) and 144 of invasive ductal carcinoma (IDC) of the breast were used. The tissue slides were immunostained for protein gene product (PGP) 9.5 and S 100 to identify nerves. The correlation between the expression of PGP 9.5 and clinicopathological characteristics in IDC of the breast was assessed. RESULTS: While the PGP 9.5 positive nerve fibers are identified in all cases of normal breast tissue controls and in the tumor stroma of 61% (89/144) cases of invasive ductal carcinomas, PGP 9.5 positive nerve fibers are not seen in the tumor stroma of cases of fibroadenoma and DCIS. The percentage of tumors that exhibited neurogenesis increased from tumor grade I to tumor grade II and III (29.4% vs 71.8%, p < 0.0001). In addition, patients with less than 3 years of disease-free survival tended to have a higher positive expression of PGP 9.5 compared to patients with an equal or more than 3 years of disease-free survival (64.8% vs 46.7%, p = 0.035). Furthermore, moderate/strong expression of PGP 9.5 was found to be significantly related to microvessel density (MVD, p = 0.014). Interestingly, PGP 9.5 expression was significantly associated with higher MVD in the ER-negative (p = 0.045) and node-negative (p = 0.039) subgroups of IDC of the breast. CONCLUSIONS: This data indicates that neurogenesis is associated with some aggressive features of IDC including tumor grade and patient survival as well as angiogenesis, especially in ER-negative and node-negative subtypes of IDC of the breast. Thus, neurogenesis appears to be associated with breast cancer progression and may play a role in therapeutic guidance for patients with ER-negative and node-negative invasive breast cancer.