Metallothionein gene expression is altered in oral cancer and may predict metastasis and patient outcomes

Histopathology. 2015 Sep;67(3):358-67. doi: 10.1111/his.12660. Epub 2015 Mar 8.

Abstract

Aims: Metallothioneins (MTs) are proteins associated with the carcinogenesis and prognosis of various tumours. Previous studies have shown their potential as biomarkers in oral squamous cell carcinoma (OSCC). Aiming to understand more clearly the function of MTs in OSCC we evaluated, for the first time, the gene expression profile of MTs in this neoplasm.

Materials and results: Tissue samples from 35 cases of tongue and/or floor of mouth OSCC, paired with their corresponding non-neoplastic oral mucosa (NNOM), were retrieved (2007-09). All tissues were analysed for the following genes using TaqMan(®) reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays: MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1X, MT2A, MT3 and MT4. The expression of MT1B and MT1H was seldom detected in both OSCC and NNOM. A significant loss of MT1A, MT1X, MT3 and MT4 expression and gain of MT1F expression was observed in OSCC, compared to NNOM. Cases with MT1G down-regulation exhibited the worst prognoses. The up-regulation of MT1X was restricted to non-metastatic cases, whereas up-regulation of MT3 was related to cases with lymph node metastasis.

Conclusions: Metallothionein mRNA expression is altered significantly in oral squamous cell carcinomas. The expression of MT1G, MT1X and MT3 may aid in the prognostic discrimination of OSCC cases.

Keywords: RT-qPCR; metallothionein; metastasis; oral squamous cell carcinoma; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / secondary
  • Down-Regulation
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 16 / genetics
  • Metallothionein / genetics*
  • Middle Aged
  • Mouth Mucosa / enzymology
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / pathology
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MMP16 protein, human
  • MT1G protein, human
  • RNA, Messenger
  • RNA, Neoplasm
  • metallothionein1X , human
  • Metallothionein
  • Matrix Metalloproteinase 16