Tumor-related markers in histologically normal margins correlate with locally recurrent oral squamous cell carcinoma: a retrospective study

J Oral Pathol Med. 2016 Feb;45(2):83-8. doi: 10.1111/jop.12334. Epub 2015 Aug 11.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is characterized by a high rate of local recurrence (LR) even when the surgical margins are considered histopathologically 'normal'. The aim of our study was to determine the relationship between early tumor-related markers detected in histologically normal margins (HNM) and LR as well as disease-free survival in OSCC.

Methods: The loss of heterozygosity (LOH) of markers on 9p21 (D9s1747, RPS6, D9s162) and 17p13 (TP53) and the immunostaining results of the corresponding mutant P53, P14, P15, and P16 proteins were assessed and correlated with LR and disease-free survival in 71 OSCC patients who had HNM.

Results: Fifteen of 71 patients with HNM developed LR. The presence of the following molecular markers in surgical margins was significantly correlated with the development of LR: LOH on chromosome 9p21 (D9s1747 + RPS6 + D9s162), any LOH, P16, and P53 (chi-square test, P < 0.05). The presence of TP53 LOH, 9p21 LOH, any LOH, P15, P16, P53, P16 + D9s1747, and P53 + TP53 had a significant effect on LR (Kaplan-Meier analysis, P < 0.05). P16 + D9s1747 was the most predictive factor using multivariate Cox analyses.

Conclusions: Detection of tumor-related markers in histologically 'normal' resection margins may be a useful method for assessing LR in OSCC patients.

Keywords: local recurrence; loss of heterozygosity; oral squamous cell carcinoma; surgical margins.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Chromosomes, Human, Pair 9
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA, Neoplasm / genetics
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / diagnosis*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / surgery
  • Humans
  • Kaplan-Meier Estimate
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / surgery
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / surgery
  • Prognosis
  • Retrospective Studies*
  • Squamous Cell Carcinoma of Head and Neck
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • TP53 protein, human
  • Tumor Suppressor Protein p53