Expression of G1/S-cyclins and cyclin-dependent kinase inhibitors in actinic keratosis and squamous cell carcinoma

J Cutan Pathol. 2016 Mar;43(3):200-10. doi: 10.1111/cup.12623. Epub 2015 Oct 19.

Abstract

Background: Actinic keratosis (AK) and Bowen's disease (squamous cell carcinoma in situ, SCCIS) are pre-invasive stages in the development of squamous cell carcinoma (SCC).

Methods: Immunohistochemical study of cyclin D1, cyclin E, p16(INK4a) and p21(Cip1) (/Waf1) in AK (53 cases), SCCIS (16 cases) and SCC (40 cases), in relation to the type of the lesion and SCC prognostic parameters (grade, diameter and thickness).

Results: Diffuse cyclin D1 distribution was more frequent in SCCIS and SCC than in AK (p = 0.03) and similar pattern was observed for p16(INK4a) . For cyclin E, central distribution dominated in SCC compared with the AK (p = 0.001) and SCCIS (p = 0.03). p21(Cip1) (/Waf1) displayed suprabasal distribution more frequently in AK than in SCCIS (p = 0.001) and SCC (p = 0.0004). Semiquantitative assessment showed more positive cells in AK (p = 0.04) and SCCIS (p = 0.04) than in SCC for cyclin E. SCC with diameter over 20 mm and those thicker than 6 mm revealed higher labeling index with p16(INK4a) and p21(Cip1) (/Waf1) , respectively.

Conclusions: Our results suggest different alterations for p16(INK4a) and p21(Cip1) (/Waf1) in AK, SCCIS and SCC. Immunostaining distribution showed closer correlation with the type of the lesion, whereas percentage of positive cells displayed better association with the SCC prognostic parameters.

Keywords: cyclin D1; cyclin E; p16; p21; squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell* / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Cyclin-Dependent Kinase Inhibitor Proteins / biosynthesis*
  • Cyclins / biosynthesis*
  • Female
  • G1 Phase*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Keratosis, Actinic* / metabolism
  • Keratosis, Actinic* / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • S Phase*
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology

Substances

  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclins
  • Neoplasm Proteins