P53/MDM2 Co-Expression in Laryngeal Squamous Cell Carcinoma Based on Digital Image Analysis

Anticancer Res. 2019 Aug;39(8):4137-4142. doi: 10.21873/anticanres.13572.

Abstract

Background: P53 is a key regulator of genomic stability and function, acting as a tumor suppressor protein. Our aim was to correlate P53 expression with murine double minute 2 (MDM2), a proto-oncogene that interacts with P53 and forms an auto-regulatory pathway, in laryngeal squamous cell carcinoma (LSCC).

Materials and methods: A total of 50 LSCC cases were included in the study. Immunohistochemistry was applied by using antibodies to P53 and MDM2 in the corresponding tissue sections. Protein expression levels for both molecules were measured by implementing a digital image analysis assay (immunostaining intensity levels, densitometric evaluation).

Results: Overexpression of P53 protein was observed in 16/50 (32%) LSCC cases, while 22/50 (44%) cases strongly expressed MDM2 protein. Interestingly, in 13/50 (26%) cases, combined overexpression of P53/MDM2 was detected. Overall P53 was strongly positively correlated with MDM2 expression (p=0.001). Both P53 and MDM2 overexpression were significantly correlated with advanced stage of LSCC (p=0.032 and p=0.001, respectively). Additionally, MDM2 was found to be associated with poorer survival of patients (p=0.046).

Conclusion: Aberrant co-expression of P53 and MDM2 is associated with advanced stage in LSCC. Furthermore, MDM2 overexpression is a frequent and critical genetic event in LSCC and seems to negatively affect survival.

Keywords: Larynx; MDM2; P53; carcinoma; digital image analysis; immunohistochemistry.

MeSH terms

  • Aged
  • Animals
  • Carcinoma, Squamous Cell / diagnostic imaging*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunohistochemistry
  • Laryngeal Neoplasms / diagnostic imaging*
  • Laryngeal Neoplasms / drug therapy
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / pathology
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • MAS1 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Mas
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2