Molecular markers in the surgical margin of oral carcinomas.
BACKGROUND
Local or regional lymph node recurrence is the most common pattern of treatment failure in oral squamous cell carcinoma (SCC). The local recurrence rate is 30% even when the surgical resection margin is diagnosed as tumour free. Accumulation of genetic changes in histologically normal epithelium in the surgical resection margin may explain the local recurrence rate. The purpose of this study is to investigate the presence of senescence markers, which may represent early malignant changes in the margin that in routine pathological evaluations are classified as histologically normal.


METHODS
Formalin-fixed, paraffin-embedded surgical specimens from 16 consecutive patients with oral SCC and a clear surgical margin were obtained. The margin was analysed by immunohistochemistry for p53, p16, Chk2, Laminin-5 and glycosylated oncofetal fibronectin.


RESULTS
Two patterns of p53 expression were found in the histologically normal epithelium in the surgical resection margin. One was characterized by no protein expression in the majority of cells, except for small clusters of basal and parabasal cells with nuclear staining. The other was characterized by p53 expression in the nuclei of most basal cells. The expression of p16 was confined to small groups of cells in the basal cell layer whereas Chk2 was only seen in one case. Upregulation of the stromal proteins, Laminin-5 or glycosylated oncofetal fibronectin, was only seen at regions of invasion.


CONCLUSIONS
Small groups of cells expressing p53 and p16 were found in the surgical resection margin that appeared to be histologically normal and may represent early malignant changes.
Bilde
Anders
A
Department of Otolaryngology-Head & Neck Surgery, Copenhagen University Hospital, Copenhagen, Denmark. bilde@rh.dk
von Buchwald
Christian
C
Dabelsteen
Erik
E
Therkildsen
Marianne Hamilton
MH
Dabelsteen
Sally
S
D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000601:surgery; D015815:Cell Adhesion Molecules / Q000032:analysis; D002467:Cell Nucleus / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D016922:Cellular Senescence; D064447:Checkpoint Kinase 2; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D003593:Cytoplasm / Q000473:pathology; D004261:DNA Replication; D004848:Epithelium / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology* / Q000601:surgery; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D017154:Stromal Cells / Q000473:pathology; D025803:Tumor Suppressor Protein p14ARF / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015854:Up-Regulation; D000097794:Kalinin
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D064447:Checkpoint Kinase 2; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005353:Fibronectins; D017346:Protein Serine-Threonine Kinases; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D000097794:Kalinin; C121542:oncofetal fibronectin; C578634:CHEK2 protein, human