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Transforming growth factor ß1 and ß2 (TGFβ 2 / TGFβ 2 ) profile changes in previously irradiated free flap beds
Author(s) -
SchultzeMosgau Stefan,
Wehrhan Falk,
Grabenbauer Gerhard,
Amann Kerstin,
RadespielTröger Martin,
Neukam Friedrich Wilhelm,
Rodel Franz
Publication year - 2002
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.10011
Subject(s) - transforming growth factor , irradiation , immunohistochemistry , medicine , wound healing , fibrosis , radiation therapy , transplantation , growth factor , pathology , urology , surgery , receptor , physics , nuclear physics
Background Following preoperative radiotherapy prior to ablative surgery of squamous epithelial carcinomas of the head and neck region, inflammatory changes and the expression of cytokines involved in wound healing could be observed. These processes lead to a delayed healing of free flaps in the graft bed. The aim of the present experimental study was to analyze the expression profiles of transforming growth factor (activated TGFβ 1 , TGFβ 2 ) and latency‐associated peptide (LAP) in the irradiated graft beds and the transition area between grafts and irradiated graft beds. Methods In Wistar rats (male, weight 300–500 g) undergoing preoperative irradiation of the neck region with 30 Gy (30 animals) and non‐irradiated rats (42 animals), a free myocutaneous gracilis flap taken from the groin was transplanted to the irradiated region of the neck. The interval between irradiation and transplantation was 4 weeks. In each group on postoperative days 3, 7, 14, and 28, cytoplasmatic expression of activated TGFβ 1 , LAP, and TGFβ 2 was analyzed by immunohistochemistry to determine labeling indices (positive stained cells/total cells). Results The success rate in graft beds irradiated with 30 Gy was 76% and in non‐irradiated graft beds was 86% ( p = .02). In the graft beds irradiated with 30 Gy, there was an increased expression of activated TGFβ 1 (range, 19.0–33.0), LAP (14.0–21.0), and TGFβ 2 (3.0–19.5) together with obvious fibrosis. The expression was located in perivascular fibroblasts and endothelial cells. In contrast, a lower expression of activated TGFβ 1 (11.0–21.0), LAP (1.0–8.0), and TGFβ 2 (0.0–0.9) ( p = .006) was observed in non‐irradiated graft beds. In the transition area between graft and irradiated graft bed, high expression of activated TGFβ 1 (37.0), LAP (19.0), and TGFβ 2 (16.7–33.4) was observed on the 3rd postoperative day in contrast to the transition area in non‐irradiated graft beds (activated TGFβ 1 26.0, LAP 7.0, and TGFβ 2 0.l). Conclusion The radiation induced, increased de novo synthesis of LAP, activation of TGFβ 1 , and increased expression of TGFβ 2 may represent at least one mechanism for the increased fibrosis and wound healing disorders seen in irradiated tissues and in the transition area to graft tissue. The expression of TGFβ 1, LAP, and TGFβ 2 might possess prognostic value with regard to wound healing and fibrosis in previously irradiated graft beds. © 2002 John Wiley & Sons, Inc. Head Neck 24: 33–41, 2002.