Context.-The ability of intermediate trophoblasts to invade maternal tissue during placentation depends on how well they can degrade the extracellular matrix. Invasion into the extracellular matrix requires many complex proteases. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a novel family of secreted metalloproteinases. The ADAMTS-1, -4, -5, and -14 subtypes are known to be expressed in human placenta, but little is understood about their expression patterns.Objective.-To examine the expression patterns of ADAMTS-1, -4, -5, and -14 in specific human placenta cell types during gestation and in gestational trophoblastic diseases.Design.-Placental tissues were obtained from 25 pregnant women and 21 cases of gestational trophoblastic diseases (10 early complete moles, 3 placental site trophoblastic tumors, 4 invasive moles, and 4 choriocarcinomas). The expression of the 4 ADAMTS was analyzed by immunohistochemistry.Results.-ADAMTS-1, -4, -5, and -14 were differentially expressed by the human placenta throughout gestation in a time-specific and cell type-specific manner, as well as in gestational trophoblastic diseases. ADAMTS-1 showed gradually strong staining intensity in gestational trophoblastic diseases according to the invasive potential but showed consistent strong intensity throughout normal placenta. ADAMTS-4 and ADAMTS-5 exhibited higher and restricted expression in first-trimester intermediate trophoblasts. They also exhibited comparably strong expression in gestational trophoblastic diseases. However, ADAMTS-14 expression remained unchanged throughout gestation.Conclusions.-The restricted expression pattern of ADAMTS-4 and ADAMTS-5 and their increased expression in gestational trophoblastic diseases suggest that these 2 ADAMTS subtypes are associated with a biological phenotype of trophoblasts involved in human placentation and the development of gestational trophoblastic diseases.
Background/Aims: Autophagy is crucial for the survival and function of plasma cells including protection from toxic misfolded immunoglobulin and proper energy metabolism. Multiple myeloma (MM) is an indolent but eventually fatal neoplasm of plasma cells. Autophagy may play a critical role in the survival of MM cells and their response to chemotherapeutic agents. In this study, we correlated the expression of autophagy-related proteins with the prognosis of MM. Methods: In this retrospective cohort study, we examined the expression of the autophagic markers BECLIN 1 and microtubule-associated protein light chain 3 (LC3) in 89 cases of MM biopsied from 2001 to 2004 at the Asan Medical Center. The association of the expression scores of these markers with clinical outcomes was assessed. Results: Patients with strong immunoreactivity to BECLIN 1 or LC3 had a significantly better overall survival (OS) than patients with negative to moderate immunoreactivity (p = 0.036 and 0.018, respectively). This was also true for disease-specific survival (DSS; p = 0.051 and 0.043, respectively). In addition, LC3 immunostaining remained an independent factor impacting OS (p = 0.028) and DSS (p = 0.020) after multivariate analysis. Conclusions: The results of this study suggest that higher immunoreactivity for autophagic markers in MM is associated with superior patient survival.
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