Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer

Silvana Papagerakis, Al Hassan Shabana, Bradley H Pollock, Petros Papagerakis, Joël Depondt, Ariane Berdal

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Down-regulation of desmosomal proteins is associated with the invasive and metastatic ability of tumor cells. We examined 37 cases of human primary oropharyngeal squamous cell carcinomas lacking overt distant metastases to gain further insights on the potential role of desmoplakin in oral cancer. Desmoplakin expression was evaluated using reverse transcriptase-polymerase chain reaction and immunohistochemistry on frozen unfixed sections. Western blotting was performed to characterize the relative expression levels for each of the 2 desmoplakin protein isoforms, I and II. Desmoplakin expression was compared with histopathological grade, clinical stage, and patient outcome. Desmoplakin expression was prominent in highly differentiated tumors and reduced or absent in poorly differentiated tumors that developed distant metastases within the 3 years of follow-up period. Desmoplakin mRNA levels tracked with protein levels, suggesting that lack of desmoplakin protein expression is due to down-regulation of mRNA expression at the transcription level. Western blot analysis demonstrated that the 2 desmoplakin isoforms displayed different patterns of subcellular distribution in tumors, with the desmoplakin II detected only in patients in which desmoplakin immunoreactivity displayed an abnormal cytoplasmic localization. Our findings suggest that down-regulation of desmoplakin expression may represent a useful marker for evaluating the risk of distant metastasis formation in oropharyngeal squamous cell carcinomas. Interestingly, desmoplakin II was detected only in tumors associated with a poor clinical outcome, suggesting a potential specific function for this isoform in oral carcinogenesis. Characterizing DSP expression may improve evaluation risk of distant metastasis formation in oral cancer patients.

Original languageEnglish (US)
Pages (from-to)1320-1329
Number of pages10
JournalHuman Pathology
Volume40
Issue number9
DOIs
StatePublished - Sep 2009
Externally publishedYes

Fingerprint

Desmoplakins
Oropharyngeal Neoplasms
Proteins
Neoplasm Metastasis
Protein Isoforms
Down-Regulation
Mouth Neoplasms
Neoplasms
Squamous Cell Carcinoma
Western Blotting
Messenger RNA
Frozen Sections
Reverse Transcriptase Polymerase Chain Reaction

Keywords

  • Adhesion
  • Desmoplakin
  • Metastasis
  • Oropharynx
  • Squamous cell carcinomas

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer. / Papagerakis, Silvana; Shabana, Al Hassan; Pollock, Bradley H; Papagerakis, Petros; Depondt, Joël; Berdal, Ariane.

In: Human Pathology, Vol. 40, No. 9, 09.2009, p. 1320-1329.

Research output: Contribution to journalArticle

Papagerakis, Silvana ; Shabana, Al Hassan ; Pollock, Bradley H ; Papagerakis, Petros ; Depondt, Joël ; Berdal, Ariane. / Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer. In: Human Pathology. 2009 ; Vol. 40, No. 9. pp. 1320-1329.
@article{35970acc3b7b470ea2b5f32be363cf28,
title = "Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer",
abstract = "Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Down-regulation of desmosomal proteins is associated with the invasive and metastatic ability of tumor cells. We examined 37 cases of human primary oropharyngeal squamous cell carcinomas lacking overt distant metastases to gain further insights on the potential role of desmoplakin in oral cancer. Desmoplakin expression was evaluated using reverse transcriptase-polymerase chain reaction and immunohistochemistry on frozen unfixed sections. Western blotting was performed to characterize the relative expression levels for each of the 2 desmoplakin protein isoforms, I and II. Desmoplakin expression was compared with histopathological grade, clinical stage, and patient outcome. Desmoplakin expression was prominent in highly differentiated tumors and reduced or absent in poorly differentiated tumors that developed distant metastases within the 3 years of follow-up period. Desmoplakin mRNA levels tracked with protein levels, suggesting that lack of desmoplakin protein expression is due to down-regulation of mRNA expression at the transcription level. Western blot analysis demonstrated that the 2 desmoplakin isoforms displayed different patterns of subcellular distribution in tumors, with the desmoplakin II detected only in patients in which desmoplakin immunoreactivity displayed an abnormal cytoplasmic localization. Our findings suggest that down-regulation of desmoplakin expression may represent a useful marker for evaluating the risk of distant metastasis formation in oropharyngeal squamous cell carcinomas. Interestingly, desmoplakin II was detected only in tumors associated with a poor clinical outcome, suggesting a potential specific function for this isoform in oral carcinogenesis. Characterizing DSP expression may improve evaluation risk of distant metastasis formation in oral cancer patients.",
keywords = "Adhesion, Desmoplakin, Metastasis, Oropharynx, Squamous cell carcinomas",
author = "Silvana Papagerakis and Shabana, {Al Hassan} and Pollock, {Bradley H} and Petros Papagerakis and Jo{\"e}l Depondt and Ariane Berdal",
year = "2009",
month = "9",
doi = "10.1016/j.humpath.2009.02.002",
language = "English (US)",
volume = "40",
pages = "1320--1329",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "9",

}

TY - JOUR

T1 - Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer

AU - Papagerakis, Silvana

AU - Shabana, Al Hassan

AU - Pollock, Bradley H

AU - Papagerakis, Petros

AU - Depondt, Joël

AU - Berdal, Ariane

PY - 2009/9

Y1 - 2009/9

N2 - Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Down-regulation of desmosomal proteins is associated with the invasive and metastatic ability of tumor cells. We examined 37 cases of human primary oropharyngeal squamous cell carcinomas lacking overt distant metastases to gain further insights on the potential role of desmoplakin in oral cancer. Desmoplakin expression was evaluated using reverse transcriptase-polymerase chain reaction and immunohistochemistry on frozen unfixed sections. Western blotting was performed to characterize the relative expression levels for each of the 2 desmoplakin protein isoforms, I and II. Desmoplakin expression was compared with histopathological grade, clinical stage, and patient outcome. Desmoplakin expression was prominent in highly differentiated tumors and reduced or absent in poorly differentiated tumors that developed distant metastases within the 3 years of follow-up period. Desmoplakin mRNA levels tracked with protein levels, suggesting that lack of desmoplakin protein expression is due to down-regulation of mRNA expression at the transcription level. Western blot analysis demonstrated that the 2 desmoplakin isoforms displayed different patterns of subcellular distribution in tumors, with the desmoplakin II detected only in patients in which desmoplakin immunoreactivity displayed an abnormal cytoplasmic localization. Our findings suggest that down-regulation of desmoplakin expression may represent a useful marker for evaluating the risk of distant metastasis formation in oropharyngeal squamous cell carcinomas. Interestingly, desmoplakin II was detected only in tumors associated with a poor clinical outcome, suggesting a potential specific function for this isoform in oral carcinogenesis. Characterizing DSP expression may improve evaluation risk of distant metastasis formation in oral cancer patients.

AB - Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Down-regulation of desmosomal proteins is associated with the invasive and metastatic ability of tumor cells. We examined 37 cases of human primary oropharyngeal squamous cell carcinomas lacking overt distant metastases to gain further insights on the potential role of desmoplakin in oral cancer. Desmoplakin expression was evaluated using reverse transcriptase-polymerase chain reaction and immunohistochemistry on frozen unfixed sections. Western blotting was performed to characterize the relative expression levels for each of the 2 desmoplakin protein isoforms, I and II. Desmoplakin expression was compared with histopathological grade, clinical stage, and patient outcome. Desmoplakin expression was prominent in highly differentiated tumors and reduced or absent in poorly differentiated tumors that developed distant metastases within the 3 years of follow-up period. Desmoplakin mRNA levels tracked with protein levels, suggesting that lack of desmoplakin protein expression is due to down-regulation of mRNA expression at the transcription level. Western blot analysis demonstrated that the 2 desmoplakin isoforms displayed different patterns of subcellular distribution in tumors, with the desmoplakin II detected only in patients in which desmoplakin immunoreactivity displayed an abnormal cytoplasmic localization. Our findings suggest that down-regulation of desmoplakin expression may represent a useful marker for evaluating the risk of distant metastasis formation in oropharyngeal squamous cell carcinomas. Interestingly, desmoplakin II was detected only in tumors associated with a poor clinical outcome, suggesting a potential specific function for this isoform in oral carcinogenesis. Characterizing DSP expression may improve evaluation risk of distant metastasis formation in oral cancer patients.

KW - Adhesion

KW - Desmoplakin

KW - Metastasis

KW - Oropharynx

KW - Squamous cell carcinomas

UR - http://www.scopus.com/inward/record.url?scp=68349145959&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68349145959&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2009.02.002

DO - 10.1016/j.humpath.2009.02.002

M3 - Article

C2 - 19386346

AN - SCOPUS:68349145959

VL - 40

SP - 1320

EP - 1329

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 9

ER -