Immunohistochemical identification and localization of endogenous endostatin and its related peptides in murine tumors.

Endostatin, a fragment of the C-terminal domain of mouse collagen XVIII, is a recently demonstrated endogenous inhibitor of tumor angiogenesis. Although endostatin can be detected in blood and urine of tumor-bearing as well as normal mice, the exact localization of the endogenous protein and its related peptides in tumor tissues is unknown. We used immunohistochemistry and immunoblotting to identify endostatin tissue location and staining patterns in tumor, as well as to determine the differences in the levels of endostatin expression between tumor cells (in vitro) and tumor tissues (in vivo). Using a specific polyclonal antibody against murine endostatin, we quantitatively determined the levels of endostatin in five murine mammary tumors and the KHT sarcoma by Western blotting. The staining patterns for this protein in tumor sections were examined histologically by immunohistochemistry. Our results show that: (1) Endogenous endostatin and its related peptides are widely distributed in all in vivo tumor types tested, but not in most of the cultured tumor cell lines. (2) Endogenous endostatin stained most tumor stromal components, including vessel walls, basement membranes, extracellular spaces, and tumor cells. (3) Staining patterns and localization of endostatin and thrombospondin-1 were similar in these tumor sections.

Is there a favorable subset of patients with prostate cancer who develop oligometastases?

OBJECTIVE: To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions. METHODS AND MATERIALS: The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival. RESULTS: The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with < or =5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with < or =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively). CONCLUSIONS: Patients with < or =5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.