Carcinosarcoma (CS), also known as metaplastic breast carcinoma with mesenchymal differentiation, is one of the five distinct subtypes of metaplastic breast cancer. It is considered as a mixed, biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition zone. Although cellular origin of this neoplasm remains controversial, most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic differentiation. Despite recent research on the therapeutic strategies against CS neoplastic disorders, surgical resection appears the only potentially curative approach. Since CS metastasize by the lymphatic route, axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always implemented. Nevertheless, the tumor also presents a hematogenous metastatic pattern including pleural, pulmonary, liver, brain and less commonly bone metastases. Thus, surgical removal of breast CS does not necessarily ensure patient's long-term recovery. Moreover, alternative therapies, such as radio- and chemotherapy proved insufficient and 5-year survival rate is limited. Nevertheless, there is evidence that following surgery, the combination of radio and chemotherapy is associated with a better prognosis than either treatment alone. The aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological spread. Clinical features, histogenesis, morphological and immunochemical findings are discussed, while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

BACKGROUND TBC1 domain family member 24 (TBC1D24) pathogenic mutations affect its binding to ARF6 and then result in severe impairment of neuronal development. However, there are no reports about the expression and function of TBC1D24 in cancer. The aim of the present study was to evaluate the effect of proliferation, migration, and invasion after silencing TBC1D24 expression in breast cancer MCF-7 cells, and to elucidate the potential mechanism of TBC1D24 in breast cancer. MATERIAL AND METHODS The expression of TBC1D24 in breast cancer tissues and the adjacent non-tumor tissues was determined by S-P immunohistochemistry. The malignant behavior, including proliferation, migration, and invasion ability, was determined after silencing TBC1D24 in breast cancer MCF-7 cells. The expression of IGF1R was determined after silencing TBC1D24. The expression of TBC1D24 and IGF1R was detected after transfecting miR-30a mimics or inhibitors. The effect of TBC1D24 on MCF-7 cells growth in vivo was evaluated by a tumor xenograft study. RESULTS TBC1D24 expression was elevated and was associated with poor outcome in breast carcinoma. TBC1D24 high expression was significantly correlated with unfavorable OS and RFS for breast cancer patients (p<0.05). Silencing TBC1D24 inhibited the proliferation, migration, and invasion ability of MCF-7 cells. TBC1D24 and IGF1R expression were decreased when transfected with miR-30a mimics. However, TBC1D24 and IGF1R expression were increased when transfected with miR-30a inhibitors (p<0.05). Knockdown of TBC1D24 inhibited the expression of IGF1R, PI3K, and p-AKT (p<0.05). Knockdown of TBC1D24 abolished tumorigenicity of MCF-7 cells. The average volume and weight of tumors was lower after silencing TBC1D24 expression (P<0.05). CONCLUSIONS Silencing TBC1D24 inhibited MCF-7 cells growth in vitro and in vivo. TBC1D24 promoted breast carcinoma growth through the IGF1R/PI3K/AKT pathway. TBC1D24 is a potential therapeutic target for breast cancer.