Expression of Ki-67 and p53 in cutaneous free flaps used to reconstruct soft tissue defects following resection of oral squamous cell carcinoma

Abstract

Radial forearm free flaps are used routinely to reconstruct oro-facial tissues following resection of oral squamous cell carcinoma. Surprisingly, there is little information regarding their behaviour following engraftment. The present report is a clinico-pathological study of 10 patients who had incisional biopsies of cutaneous free flaps after the presence of a white patch or erythema raised clinical suspicion. Tissues were stained with haematoxylin and eosin, diastase-periodic acid-Schiff reagent and labelled immunohistochemically for Ki-67 and p53. Four of 10 specimens showed severe epithelial dysplasia within the graft, which was contiguous with dysplasia in the adjacent oral mucosa; the remaining grafts had features typical of candidosis (n=4) or hyperkeratosis (n=2). Grafts with dysplasia had a significantly higher Ki-67 labelling index than lesions in the 'non-dysplastic' group. There were no significant differences in the Ki-67 labelling index between areas of dysplasia in the graft and areas of dysplasia in the adjacent oral epithelium. p53 staining was present in all strata of the epithelium in the dysplastic grafts and adjacent dysplastic mucosa, but was absent or weakly expressed in the stratum basale of grafts showing reactive changes only. None of the dysplastic lesions progressed to carcinoma despite a mean follow-up period of 32 months; one patient developed a recurrent mucosal tumour at the resection margin. These observations indicate that cutaneous free flaps grafted to a site of field cancerisation can develop severe epithelial dysplasia with concomitant deregulation of proliferation and increased p53 expression. Such changes raise the possibility that these lesions have the potential for malignant transformation.