Inhibin/activin subunits (inhibin-α, -βA and -βB) are differentially expressed in human breast cancer and their metastasis

Abstract

Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH-alpha) and one of two possible beta-subunits (INH-betaA or -betaB). Aims of this study were to determine the frequency and tissue distribution of INH-alpha, -betaA and -betaB in breast cancer tissue. Paraffin-fixed ductal carcinoma in situ (DCIS; n=7), invasive ductal carcinomas without lymph node metastases (IDC; n=8), infiltrating ductal carcinomas with their lymph node metastases (IDC/LN; n=8), primary ductal carcinomas with their subsequent recurrence (n=7) were analyzed by immunohistochemical means with monoclonal antibodies against inhibin-alpha, -betaA and -betaB subunits. INH-alpha was observed in DCIS (5/7), while its expression was significantly higher in DCIS than IDC (1/7; p<0.05) and IDC/LN (0/8; p<0.005) and recurrent breast cancer tissue (0/7; p<0.005). The INH-betaA subunit was also demonstrated in all DCIS cases with a significantly higher intensity compared to IDC (p<0.05), IDC/LN (p<0.01) and primary carcinoma with subsequent recurrence (p<0.05). INH-betaA expression was significant higher in primary tumors with subsequent recurrence compared to IDC/LN (p<0.05). The metastatic lymph nodes expressed the lowest inhibin-betaA compared to all other groups (p<0.01). INH-betaB was also demonstrated in all mammary carcinoma tissues, but without any statistical differences. The differential expression of INH-alpha in DCIS might suggest a function as a tumor suppressor in breast tissue, suggesting a useful marker for recognizing patients with subsequent risk of developing invasive ductal cancer. The higher INH-betaA expression in DCIS than invasive cancer suggests an important role in mammary carcinogenesis. Interestingly, primary breast tumor with a subsequent recurrence expressed a higher intensity of the inhibin-betaA subunit, suggesting an important role in metastatic pathogenesis, and utilization as a tumor marker. The immunoreactivity of inhibin-betaA was significantly higher in DCIS than invasive ductal carcinomas, suggesting an important role in mammary carcinogenesis. The metastatic lymph nodes expressed lower INH-betaA and -betaB than the primary tumor, which might be the cause of less differentiated and aggressive tumor cells within the primary tumor. Therefore, inhibin/activin subunits might be useful prognostic markers for breast cancer.