In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor-negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer-induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells.
Twenty cases of metastatic neoplasms in the breast were identified in a series of 1,034 fine-needle aspirations (FNAs) of the breast, of which 389 were malignant. Patients with breast carcinomas in whom metastasis to the contralateral breast developed were excluded from this study. This series consisted of 17 women and 3 men, ranging in age from 28 to 63 years (mean, 49 years). The tumors included oat cell carcinoma (three), melanoma (three), ovarian serous carcinoma (one), bronchogenic adenocarcinoma and squamous carcinoma (four and two, respectively), lymphoma (two), carcinoid (two), transitional cell carcinoma (one), plasma cell myeloma (one), and rhabdomyosarcoma (one). In two patients, the breast mass was the first manifestation of an extramammary cancer (two adenocarcinoma of the lung). Eleven patients died of disseminated cancer shortly after the breast metastasis was diagnosed. In most cases, the aspirates displayed the cytologic features characteristic of the primary tumors, thereby establishing the metastatic nature of the neoplasm. In four cases (two carcinoids, one myeloma, and one rhabdomyosarcoma), the cytologic features were difficult to differentiate from a primary breast carcinoma; however, the final diagnosis was established by electron microscopic examination and immunocytochemical studies on the aspirates. One case (adenocarcinoma of the lung) was misdiagnosed as primary breast carcinoma on both FNA and mastectomy specimen. Because metastatic neoplasms in the breast may mimic primary breast tumors, the authors recommend the following: (1) Evaluation of FNA of breast should be done with complete knowledge of the patient's clinical history. (2) The possibility of metastasis should be suspected in lesions with unusual cytologic patterns. (3) Ancillary studies on FNA can be helpful in interpreting selected cases.
Background: Hematopoietic stem cell transplantation is being increasingly used in cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell transplant, results from bacterial, viral and fungal infections, coagulopathy, and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage associated with Strongyloides stercoralis hyperinfection in stem cell transplant patients has been rarely reported.
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