Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma

BACKGROUND: Diagnosis of ductal carcinoma in situ (DCIS) in breast cancer cases is challenging for pathologist due to a variety of in situ patterns and artefacts, which could be misinterpreted as stromal invasion. Microinvasion is detected by the presence of cytologically malignant cells outside the confines of the basement membrane and myoepithelium. When malignant cells invade the stroma, there is tissue remodeling induced by perturbed stromal-epithelial interactions. Carcinoma-associated fibroblasts (CAFs) are main cells in the microenvironment of the remodeled tumor-host interface. They are characterized by the expression of the specific fibroblast activation protein-alpha (FAP-α), and differ from that of normal fibroblasts exhibiting an immunophenotype of CD34. We hypothesized that staining for FAP-α may be helpful in determining whether DCIS has microinvasion. METHODS: 349 excised breast specimens were immunostained for smooth muscle actin SMA, CD34, FAP-α, and Calponin. Study material was divided into 5 groups: group 1: normal mammary tissues of healthy women after plastic surgery; group 2: usual ductal hyperplasia (UDH); group 3: DCIS without microinvasion on H & E stain; group 4: DCIS with microinvasion on H & E stain (DCIS-MI), and group 5: invasive ductal carcinoma (IDC). A comparative evaluation of the four immunostains was conducted. RESULTS: Our results demonstrated that using FAP-α and Calponin adjunctively improved the sensitivity of pathological diagnosis of DCIS-MI by 11.29%, whereas the adjunctive use of FAP-α and Calponin improved the sensitivity of pathological diagnosis of DCIS by 13.6%. CONCLUSIONS: This study provides the first evidence that immunostaining with FAP-α and Calponin can serve as a novel marker for pathologically diagnosing whether DCIS has microinvasion.