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Correlation of clinicopathological features with immunohistochemical expression of cell cycle regulatory proteins p16 and retinoblastoma: distinct association with keratinisation and differentiation in oral cavity squamous cell carcinoma
  1. D M Muirhead1,
  2. H T Hoffman2,
  3. R A Robinson1
  1. 1Departments of Pathology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa, USA
  2. 2Departments of Otolaryngology—Head and Neck Surgery, Roy J and Lucille A Carver College of Medicine
  1. Correspondence to:
 R A Robinson
 Department of Pathology, Roy J and Lucille A Carver College of Medicine, 5232 RCP, 200 Hawkins Drive, University of Iowa, Iowa City, Iowa, 52242, USA; robert-a-robinson{at}


Background: The p16 and retinoblastoma (Rb) gene products are part of the retinoblastoma pathway controlling the G1–S transition of the cell cycle. Few studies on the expression of p16 and retinoblastoma proteins in oral cavity squamous carcinomas have been conducted.

Aim: To correlate the expression of p16 and retinoblastoma proteins to clinicopathological characteristics in these tumours.

Methods: 45 patients with resected oral cavity squamous carcinoma were selected, for whom this was the initial treatment and who were followed up for 5 years or until death. Immunohistochemical stains with antibodies to the Rb and p16 gene products were carried out on paraffin wax-embedded tissue. Data on clinicopathological features such as tumour differentiation, nodal status, stage and survival outcome were collected.

Results: Retinoblastoma expression was seen in 39 of 45 (87%) patients and p16 expression in 6 of 45 (13%) patients. A significant inverse correlation was observed between retinoblastoma and p16 expression as nearly all retinoblastoma negative cases were p16 positive, and vice versa. When examined for clinicopathological correlates, it was found that all 39 tumours that expressed retinoblastoma displayed marked keratinisation and were of low–moderate histological grade. Conversely, five of the six tumours that expressed p16 were found to be poorly differentiated, with minimal keratin expression.

Conclusions: Salient relationships were seen between expression of retinoblastoma and p16 and keratinisation. A marked loss of keratin production was evident in the tumours that expressed p16. Tumours expressing retinoblastoma were seen to exhibit more widespread keratinisation. In addition, an inverse staining pattern was found for retinoblastoma and p16 as retinoblastoma-expressing tumours were nearly universally p16 negative and vice versa. No correlation of expression of either p16 or retinoblastoma was found with survival or stage. A link between the histologically observable morphology and expression of cell cycle regulatory protein with the expression of p16 and retinoblastoma has been suggested with keratinisation and differentiation of status.

  • CDKs, cyclin-dependent kinases
  • Rb, retinoblastoma gene

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  • Published Online First 6 February 2006

  • Competing interests: None.

  • Ethical approval: The University of Iowa institutional review board approved this work.