Author: Nat Pernick, M.D. (see Authors page)

Revised: 1 December 2015, last major update July 2013

Copyright: (c) 2002-2015,, Inc.

Cite this page: Rb. website. Accessed May 27th, 2018.
Definition / general
  • Retinoblastoma gene / protein
  • Tumor suppressor gene at 13q14
  • Encodes a 110-114 kDa nuclear protein that plays a crucial role in cell cycle progression by regulating cell cycle arrest at G1-S
  • Active form is hypophosphorylated and binds to E2F family of transcription factors, which bind to DNA to inhibit transcription
  • Inactive form is phosphorylated via cyclin D-CDK4 / CDK6 complexes, which are inhibited by p16INK4a
  • Rb inactivity (leading to transcription) caused by (a) loss of p16INK4a causing phosphorylation of Rb, making it inactive; (b) Rb mutations; (c) Rb hyperphosphorylation; (d) overexpression of cyclin D; (e) DNA tumor virus SV40 T antigen, adenovirus E1A and HPV-E7 protein
  • Inactive Rb is reactivated by cell cycle specific phosphatase in M phase
  • Germline mutations or loss predispose to retinoblastoma and osteosarcoma
  • Somatic mutations cause various tumors
  • Point mutations inhibits Rb-1 and c-myc binding
  • For thyroid neoplasms, follicular adenomas were usually positive, follicular and papillary carcinomas were usually negative (Mod Pathol 2000;13:562)
Microscopic (histologic) images

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Soft tissue, neck: spindle cell lipoma; right two-loss of Rb protein

Images hosted on

Fig B, D and F

Prominent infiltrating lymphocytes (fig B)

Positive staining - normal
  • Fibroblasts, endothelial cells and lymphoid cells within thyroid neoplasms