Los Angeles, Calif.; and Toronto, Ontario, Canada From the Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles; the Research Institute, The Hospital for Sick Children; and the Divisions of Orthopedic Surgery and Plastic Surgery, Department of Surgery, and the Department of Physiology, University of Toronto.
Plast Reconstr Surg. 2010 Feb;125(2):437-445. doi: 10.1097/PRS.0b013e3181c82d05.
Capsular contracture is the main complication in postmastectomy tissue expander and implant breast reconstruction in patients requiring radiotherapy. There is evidence that the wingless signaling pathway plays a central role in the pathogenesis of fibroproliferation in fibromatosis and hyperplastic skin wounds, involving multiple linked events leading to up-regulation of target genes and fibroproliferation. Here, the authors tested their hypothesis that the wingless signaling pathway may also regulate radiotherapy-induced fibroproliferation in capsular tissue around expanders/implants in breast reconstruction.
Biopsies of the periprosthetic capsule were obtained from patients undergoing bilateral expander breast reconstruction in which one side was radiated and the other side was not radiated. Capsular biopsies were snap-frozen and stored at -80 degrees C for Western blot assays to determine protein content of phospho-glycogen-synthase-kinase-3beta (phospho-GSK-3beta), total GSK-3beta, beta-catenin, cyclooxygenase-2 (COX-2), and collagen types I and III (n = three to five patients), normalized to beta-actin. Immunostaining for beta-catenin in radiated and nonradiated capsular tissue was also performed. Slides were scanned and analyzed using Zeiss Mirax Scan.
The following protein content levels were significantly (p < 0.01) increased in radiated capsule compared with nonradiated capsule: phospho-GSK-3beta (6.7-fold), total GSK-3beta (3.0-fold), beta-catenin (2.3-fold), COX-2 (2.8-fold), and collagen type I (1.6-fold) and type III (1.8-fold). Immunohistochemical staining demonstrated increased fibroblast cytosolic beta-catenin staining and evidence of beta-catenin nuclear translocation in radiated compared with nonradiated capsular tissue.
Results from this study highlight the importance of the wingless signaling pathway in the pathogenesis of radiation-induced fibroproliferation associated with capsular contracture in expander/implant breast reconstruction.
包膜挛缩是接受放疗的患者接受乳房切除术后组织扩张器和植入物乳房重建的主要并发症。有证据表明，无翅信号通路在纤维瘤病和增生性皮肤伤口的纤维增生发病机制中起着核心作用，涉及多个相关联的事件，导致靶基因的上调和纤维增生。在这里，作者测试了他们的假设，即无翅信号通路也可能调节乳房重建中扩张器/植入物周围包膜组织中的放疗诱导的纤维增生。
从接受双侧扩张器乳房重建的患者中获得假体周围包膜的活检，其中一侧接受放疗，另一侧未接受放疗。将包膜活检样本迅速冷冻并储存在-80°C 下，用于 Western blot 测定以确定磷酸化糖原合成酶激酶-3β（磷酸化-GSK-3β）、总 GSK-3β、β-连环蛋白、环氧化酶-2（COX-2）和胶原蛋白 I 和 III 的蛋白含量（n = 三到五名患者），并与β-肌动蛋白归一化。还对放射和非放射包膜组织中的β-连环蛋白进行了免疫染色。使用 Zeiss Mirax Scan 扫描和分析幻灯片。
与非放射包膜相比，放射包膜中的以下蛋白含量水平显著增加（p < 0.01）：磷酸化-GSK-3β（6.7 倍）、总 GSK-3β（3.0 倍）、β-连环蛋白（2.3 倍）、COX-2（2.8 倍）和胶原蛋白 I（1.6 倍）和 III 型（1.8 倍）。免疫组织化学染色显示，与非放射包膜组织相比，放射包膜组织中纤维母细胞胞质β-连环蛋白染色增加，并且存在β-连环蛋白核转位的证据。
本研究的结果强调了无翅信号通路在与扩张器/植入物乳房重建中包膜挛缩相关的放射诱导纤维增生发病机制中的重要性。
