Tumor endothelial marker 8 overexpression in breast cancer cells enhances tumor growth and metastasis.

Tumor vasculature is known to express high levels of the longest splice variant of tumor endothelial marker 8 (TEM8). Little is known about its expression by tumor cells. Five of eight cell breast cancer cell lines tested expressed significant levels of the longest TEM8 splice variant (TEM8.1), and to a lesser extent, the shortest splice variant (TEM8.3). Breast cancer cell lines expressing high levels of TEM8 are known to be more invasive and typify a more aggressive basal-like phenotype. In vivo studies in the 4T1 murine model showed enhanced tumor growth associated with increased tumor vascularity and metastasis to lymph nodes and lungs. These data suggest that TEM8.1 expression in breast cancer cells confers a more aggressive, proangiogenic phenotype.

Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis.

BACKGROUND: Differentiated thyroid cancer has a good prognosis and only rarely presents with distant metastasis at diagnosis. The clinical outcome of this presentation was assessed with respect to survival and factors that may determine prognosis. METHODS: A retrospective review was undertaken of patients with stage M1 differentiated thyroid cancer at presentation (n = 49), referred from 1980-2000 at a single institution. RESULTS: The median age was 68 (range, 17-90), with 69% females. The initial site(s) of metastasis were lung only, 45%, bone only, 39%, other single site, 4%, and multiple sites, 12%. HISTOLOGY: papillary, 51%, follicular, 49%. Initial treatment(s) included: thyroidectomy, 82%, radioactive iodine (RAI), 88%, excision of metastasis, 29%, radiotherapy, 47%, and chemotherapy, 6%. With a median follow-up time of 3.5 years, 25 patients are alive (51%) and 24 died (49%), with 3-year and 5-year actuarial survivals of 69% and 50%, respectively. Only a minority of patients (4/25, 16%) had no clinical evidence of disease at last follow-up. Most deaths (17/24, 71%) were due to progressive cancer. Prognosis was associated with age, site of metastasis, histology, and iodine avidity of the metastasis. Patients aged 45 years (P = .001). The 3-year survival for lung only versus bone only metastasis was 77% versus 56% (P = .02); for papillary versus follicular carcinoma, 75% versus 62% (P = .006); for iodine-avid disease (n = 29) versus not avid (n = 14), 82% versus 57% (P = .02), respectively. In multivariate analysis after adjusting for age, only histology and iodine avidity remained significant for survival. The hazard ratio for follicular histology was 3.7 (95% confidence interval [CI], 1.1-12.1, P = .03), and for tumors not avid for iodine, 3.4 (95% CI, 1.2-9.2, P = .02). CONCLUSIONS: The data support the aggressive management of patients presenting with stage M1 thyroid cancer, with thyroidectomy and RAI. Complete clinical eradication of disease was rarely seen, and 50% of patients survived for more than 5 years. Young patients with papillary tumors and/or iodine-avid disease have an even better prognosis.