TY - JOUR

T1 - Molecular markers in the surgical margin of oral carcinomas

AU - Bilde, Anders

AU - von Buchwald, Christian

AU - Dabelsteen, Erik

AU - Therkildsen, Marianne Hamilton

AU - Dabelsteen, Sally

PY - 2009/1

Y1 - 2009/1

N2 - 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.CONCLUSION: 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.

AB - 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.CONCLUSION: 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.

KW - Adult

KW - Aged

KW - Basement Membrane

KW - Carcinoma, Squamous Cell

KW - Cell Adhesion Molecules

KW - Cell Aging

KW - Cell Nucleus

KW - Cell Transformation, Neoplastic

KW - Checkpoint Kinase 2

KW - Cyclin-Dependent Kinase Inhibitor p16

KW - Cytoplasm

KW - DNA Replication

KW - Epithelium

KW - Female

KW - Fibronectins

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Middle Aged

KW - Mouth Mucosa

KW - Mouth Neoplasms

KW - Neoplasm Invasiveness

KW - Neoplasm Staging

KW - Protein-Serine-Threonine Kinases

KW - Stromal Cells

KW - Tumor Markers, Biological

KW - Tumor Suppressor Protein p14ARF

KW - Tumor Suppressor Protein p53

KW - Up-Regulation

U2 - 10.1111/j.1600-0714.2008.00715.x

DO - 10.1111/j.1600-0714.2008.00715.x

M3 - Journal article

C2 - 19192052

VL - 38

SP - 72

EP - 78

JO - Journal of Oral Pathology and Medicine

JF - Journal of Oral Pathology and Medicine

SN - 0904-2512

IS - 1

ER -