Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer

Head Neck. 2017 Feb;39(2):326-333. doi: 10.1002/hed.24584. Epub 2016 Sep 21.

Abstract

Background: Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited.

Methods: In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases.

Results: CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers.

Conclusion: Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017.

Keywords: CCND1; biomarker; cyclin D1; early oral cancer; occult nodal metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy, Needle
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cortactin / genetics
  • Cyclin D1 / genetics*
  • Databases, Factual
  • Early Diagnosis
  • Fas-Associated Death Domain Protein / genetics
  • Female
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Mouth Floor / pathology
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology*
  • Netherlands
  • Observer Variation
  • Predictive Value of Tests
  • Prognosis
  • ROC Curve
  • Reproducibility of Results
  • Retrospective Studies
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / pathology

Substances

  • CCND1 protein, human
  • Cortactin
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Cyclin D1