Pro-inflammatory cytokine, matrix metalloproteinases and TIMP-1 are involved in wound healing after mastectomy in invasive breast cancer patients.
BACKGROUND
Mastectomy provides a good model to study the wound healing process after surgery. The involved factors include selectins, pro-inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinases (MMPs), and their natural inhibitors (TIMPs). In the present study, we observed the kinetic changes of these factors in the process of wound healing after a mastectomy, and analyzed the relationship between these factors and the clinical outcomes.


METHODS
Twenty-nine patients, who received a modified radical mastectomy, were recruited to this study. The wound was inspected daily for the presence of flap necrosis, infection and seroma. Drain fluid was collected on days 1, 2 and 5. IL-6, P-selectin, MMP-2, 3, 9 and TIMP-1 were screened by ELISA kits for their impacts on wound healing after mastectomy.


RESULTS
IL-6 demonstrated the highest level on Day 1 after operation and was negatively correlated with MMP-2, which in turn showed a consistently negative correlation with MMP-9 for days 1, 2 and 5. Incidences of seroma formation and skin flap necrosis were 27.6% and 20.7%, respectively. Seroma formation was associated with low MMP-2 levels on Day 5. While skin flap necrosis seemed to correlate with high MMP-2 levels and low levels of MMP-9 and TIMP-1.


CONCLUSIONS
IL-6, P-selectin, MMP-2, MMP-3, MMP-9 and TIMP-1 are important in the process of wound healing after mastectomy. A low MMP-2 level correlates with the formation of seroma, while MMP-2, MMP-9 and TIMP-1 are associated with skin flap necrosis.
Loo
Wings T Y
WT
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Sasano
H
H
Chow
Louis W C
LW
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D016207:Cytokines / Q000032:analysis / Q000502:physiology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000502:physiology; D007700:Kinetics; D008408:Mastectomy / Q000009:adverse effects*; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D009336:Necrosis; D009361:Neoplasm Invasiveness / Q000473:pathology; D019007:P-Selectin / Q000032:analysis / Q000502:physiology; D049291:Seroma / Q000473:pathology; D013524:Surgical Flaps / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000502:physiology*; D016896:Treatment Outcome; D014945:Wound Healing / Q000502:physiology*
D016207:Cytokines; D015850:Interleukin-6; D019007:P-Selectin; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases