Retroperitoneal liposarcomas: Follow‐up analysis of dedifferentiation after clinicopathologic reexamination of 86 liposarcomas and malignant fibrous histiocytomas

Abstract

Differentiation of prevalvular mesenchyme into valve fibroblasts is an integral step towards the development of functionally mature cardiac valves. Although clinically relevant, little is known regarding the molecular and cellular mechanisms by which this process proceeds. Genes that are regulated in a spatio‐temporal pattern during valve remodeling are candidates for affecting this differentiation process. Based on its expression pattern, we have focused our studies on the role of the matricellular gene, periostin, in regulating the differentiation of cushion mesenchymal cells into valve fibroblasts. Herein, we demonstrate that periostin expression is coincident with and regulates type I collagen protein production, a major component of mature valve tissue. Adenoviral‐mediated knock‐down of periostin in atrioventricular mesenchyme resulted in a decrease in collagen I protein expression and aberrant induction of myocyte markers indicating an alteration in AV mesenchyme differentiation. In vitro analyses using a novel “cardiotube” assay further demonstrated that expression of periostin regulates lineage commitment of valve precursor cells. In these cells, expression of periostin and collagen I are regulated, in part, by TGFβ‐3. We further demonstrate that TGFβ‐3, through a periostin/collagen pathway, enhances the viscoelastic properties of AV cushion tissue surface tension and plays a crucial role in regulating valve remodeling. Thus, data presented here demonstrate that periostin, a TGFβ‐3 responsive gene, functions as a crucial mediator of chick AV valve maturation via promoting mesenchymal‐to‐fibroblast differentiation while blocking differentiation of alternative cell types (myocytes). Developmental Dynamics 238:1052–1063, 2009. © 2009 Wiley‐Liss, Inc.

Liposarcomas of the posterior mediastinum: clinicopathologic study of 18 cases

“…19 In the recent literature, cases of dedifferentiated liposarcoma have been reported in all mediastinal compartments and have shared similar clinicopathologic features with those arising in the retroperitoneum. 22,27 Only four cases of de-differentiated liposarcoma of the posterior mediastinum have been reported before this study; 14,18,22 the present study contributes three additional cases. Leiomyosarcomatous differentiation is a rare phenomenon that can be found in liposarcomas 28,29 and is characterized by focal areas of smooth muscle differentiation.…”

Second Primary Malignancies in Patients with Well-differentiated/Dedifferentiated Liposarcoma

“…Liposarcomas are usually very large at the time of detection, with a typical size of 20-30 cm. In fact, these are probably the largest tumors in the human body (see Figure 1) (28). The growth rate and progression of liposarcoma prior to detection is poorly defined, and therefore it is possible that these tumors may have been present in a smaller, clinically occult form while the other cancer was detected (and even treated) or vice versa.…”

Management of retroperitoneal liposarcoma: A case report and review of the literature

“…Even with complete removal of the liposarcoma, prognosis remains poor. The 5-year survival rate of well-differentiated retroperitoneal liposarcoma is 83%, while it is 20% for the dedifferentiated tumor subtype (4). Successful complete resection of retroperitoneal liposarcoma may increase the 5-year survival rate.…”