HIPK2 expression in progression of cutaneous epithelial neoplasm

Int J Dermatol. 2015 Mar;54(3):347-54. doi: 10.1111/ijd.12664.


Background: Homeodomain-interacting protein kinase 2 (HIPK2) is responsible for a DNA damage response, centrally regulating p53. The aberrant HIPK2 expression is known to be involved in carcinogenesis in several malignancies. However, the correlation of HIPK2 expression along with progression of cutaneous epithelial neoplasm has not been investigated.

Methods: Using immunohistochemistry and real-time reverse transcription-polymerase chain reaction, we examined the correlation between HIPK2 and HIPK2-related protein expressions and the progression of some cutaneous epithelial neoplasms (i.e., actinic keratosis, Bowen's disease, keratoacanthoma, squamous cell carcinoma, and basal cell carcinoma).

Results: HIPK2 expression was distinct between preinvasive and invasive lesions: the expression decreased in keratoacanthoma (none of eight) and squamous cell carcinoma (five of 35) compared to actinic keratosis (12 of 19) and Bowen's disease (10 of 23) (P < 0.001). HIPK2 expression was also negatively correlated with aggressiveness of basal cell carcinoma; high-risk subtypes showed lower HIPK2 expression than did low-risk subtypes (P < 0.001). HIPK2 mRNA expression of each tumor group was significantly higher than that of normal skin. HIPK2 mRNA expression of each tumor group was not correlated with the relevant HIPK2 protein expression, which was consistent with previous studies.

Conclusions: HIPK2 expression tends to be decreased along tumor progression and may be involved with the invasive potential, suggesting a possible tumor suppressor role for HIPK2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bowen's Disease / chemistry*
  • Bowen's Disease / genetics
  • Bowen's Disease / pathology
  • Carcinoma, Basal Cell / chemistry*
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carrier Proteins / analysis*
  • Carrier Proteins / genetics
  • Disease Progression
  • Female
  • Gene Expression
  • Humans
  • Keratoacanthoma / genetics
  • Keratoacanthoma / metabolism*
  • Keratoacanthoma / pathology
  • Keratosis, Actinic / genetics
  • Keratosis, Actinic / metabolism
  • Keratosis, Actinic / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Protein-Serine-Threonine Kinases / analysis*
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins c-mdm2 / analysis
  • RNA, Messenger / analysis*
  • Skin Neoplasms / chemistry*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Tumor Suppressor Protein p53 / analysis


  • Carrier Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • HIPK2 protein, human
  • Protein-Serine-Threonine Kinases