Radiation-induced changes in skin type I and III collagen synthesis during and after conventionally fractionated radiotherapy.
OBJECTIVE
To measure local changes of collagen metabolism in irradiated breast skin and systemic changes in serum during and after radiotherapy and correlate these changes with skin thickness, erythema and palpable subcutaneous induration.


METHODS
Aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP, respectively) were measured from skin suction blister fluid (SBF) in 21 breast cancer patients with breast conserving surgery and conventionally fractionated radiotherapy (RT) to a total dose of 50Gy. Suction blisters were induced in the operated and contralateral breast skin before RT, at 2.5 weeks, at the end of RT, and at 1, 4, 7, 12 and 24 months post-treatment. Blood samples for serum were taken simultaneously with SBF induction. Skin thickness of the suction blister sites was measured with a high-frequency ultrasound device. The investigated sites were scored for erythema at the end of RT and palpable subcutaneous induration at 1 and 2 years post-treatment.


RESULTS
In SBF the mean levels of PINP and PIIINP of the operated breast before RT were about 3-4 times higher than those in the contralateral breast due to the operation-related wound healing. The synthesis of PINP in irradiated breast after RT increased 7.7-fold (P < 0.001) 4 months post-irradiation. The PIIINP synthesis was at maximum at 1 month post-irradiation (P < 0.001). Both synthesis stayed elevated until 2 years. The level of PINP correlated significantly with the palpable skin induration at 1 and 2 years (P = 0.038 and P = 0.003, respectively). The skin thickness of the irradiated breast was highest at 4 months post-treatment and significantly elevated until 1 year. The skin thickness correlated with the PINP level until 7 months and with PIIINP between 4 and 18 months. The PINP/PIIINP ratio reached the maximum at 4 months and stayed elevated until 2 years. No change in mean serum level of PINP was found during or after RT.


CONCLUSIONS
We demonstrated a maximum and elevated levels for PINP and PIIINP skin collagen metabolism determined from SBF during the 2 years' follow-up. Elevated levels of PINP and PIIINP correlated with the thickening of the skin and subcutaneous induration but not with erythema.
Keskikuru
Riitta
R
Department of Oncology, Kuopio University Hospital, FIN-70210 Kuopio, Finland.
Jukkola
Arja
A
Nuutinen
Jouni
J
Kataja
Vesa
V
Risteli
Juha
J
Autio
Pekka
P
Lahtinen
Tapani
T
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000532:radiotherapy*; D024042:Collagen Type I / Q000096:biosynthesis*; D024061:Collagen Type III / Q000096:biosynthesis*; D019583:Dose Fractionation, Radiation; D004890:Erythema / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D010446:Peptide Fragments / Q000096:biosynthesis; D011347:Procollagen / Q000096:biosynthesis; D012867:Skin / Q000033:anatomy & histology / Q000378:metabolism / Q000528:radiation effects*
D024042:Collagen Type I; D024061:Collagen Type III; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide