Faculty Bibliography

BACKGROUND: Androgen receptor (AR) expression in breast cancers may serve as a prognostic and predictive marker. We examined the expression pattern of AR and its phosphorylated forms, Ser-213 (AR-Ser[P]-213) and Ser-650 (AR-Ser[P]-650), in breast cancer and evaluated their association with clinicopathological parameters. METHODS: Immunohistochemistry was performed on primary and distant metastatic breast cancers and benign breast tissue using antibodies against AR, AR-Ser(P)-213, and AR-Ser(P)-650. The levels of cytoplasmic and nuclear expression were scored semiquantitatively using a histoscore. RESULTS: Nuclear staining of AR was observed in all benign breast tissue and 67% of cancer cases. Nuclear and cytoplasmic AR-Ser(P)-213 was increased in breast cancers 2-fold (P = .0014) and 1.7-fold (P = .05), respectively, compared with benign controls, whereas nuclear and cytoplasmic AR-Ser(P)-650 expression was decreased in tumors by 1.9-fold and 1.7-fold (both P < .0001), respectively. Increased expression of nuclear or cytoplasmic AR-Ser(P)-213 was observed in metastatic breast cancers (1.3-fold, P = .05), ER-negative (2.6-fold, P = .001), and invasive ductal carcinoma (6.8-fold, P = .04). AR-Ser(P)-650 expression was downregulated in lymph node-positive breast cancers (1.4-fold, P = .02) but was upregulated in invasive ductal carcinomas (3.2-fold, P < .0001) and metastases (1.5-fold, P = .003). Moreover, in ER-negative breast cancers, nuclear AR-Ser(P)-650 was decreased (1.4-fold, P = .005), and cytoplasmic AR-Ser(P)-650 was increased (1.4-fold, P = .003). CONCLUSIONS: AR and its phosphorylation at serines 213 and 650 are differentially expressed in breast cancer tumorigenesis and progression. Phosphorylation of AR at serines 213 and 650 is increased in ER-negative breast cancers, ductal carcinomas, and metastases and may have predictive value in breast cancer prognosis. Cancer 2013;000:000-000. (c) 2013 American Cancer Society.

Primary cardiac synovial sarcoma is a rare malignancy, comprising approximately 5% of cardiac sarcomas and fewer than 0.1% of all primary cardiac tumors. Synovial sarcoma is typically characterized by a t(X;18)(p11.2;q11.2) translocation resulting in fusion of the SS18 (aka SYT) gene on chromosome 18 with the SSX1, 2, or 4 genes on the X chromosome.We report a case of primary pericardial synovial sarcoma in a 42-year-old man with dyspnea. Imaging studies showed an 8.0 x 4.8 cm enhancing pericardial mass compressing the left atrium and a large pericardial effusion with compression effect consistent with tamponade. The patient underwent partial surgical resection of the mass. Histologic examination revealed an invasive malignant neoplasm with fascicles and sheets of uniform spindle cells with pleomorphic nuclei and many mitoses (7 per 10 HPF). This monophasic pattern raises a differential diagnosis including synovial sarcoma, fibrosarcoma, epithelial sarcoma, and leiomyosarcoma. The diagnosis of synovial sarcoma was confirmed by interphase FISH on FFPE tissue with an SS18 break-apart probe that was positive for an SS18 rearrangement. The patient underwent adjuvant chemotherapy and radiotherapy. He survives at 9 months after diagnosis with residual tumor growing rapidly. A review of the literature reveals 40 case reports of primary synovial sarcoma of the heart. The mean age is 36 years with a M/F ratio of 2.25. The most common locations are pericardium (13 cases) and right atria (12). Seventeen cases are monophasic type, of which 11 have confirmed t(X;18) translocations by cytogenetics, FISH, and/or RT-PCR. The prognosis is poor; 11 patients died during the first year after diagnosis. FISH provides a valuable tool for the diagnosis of synovial sarcoma, especially for challenging cases in uncommon locations (eg, heart). Identification of patients with the SS18 translocation is important for future targeted therapies