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Eur J Oral Sci. 2018 Aug;126(4):251-262. doi: 10.1111/eos.12426. Epub 2018 Jun 15.

Alterations in desmosomal adhesion at protein and ultrastructure levels during the sequential progressive grades of human oral tumorigenesis.

Author information

1
Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, India.
2
Department of Clinical Medicine and Centre for Cancer Biomarkers, Haukeland University Hospital, University of Bergen, Bergen, Norway.
3
Oral Surgery, Head and Neck Unit, Tata Memorial Hospital, Mumbai, Maharashtra, India.
4
Epidemiology and Clinical Trials Unit, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, India.
5
Department of Neurological Surgery, Northwestern University, Chicago, IL, USA.
6
Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
7
Department of Medical Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Hospital, Kharghar, Navi Mumbai, Maharashtra, India.
8
Department of Biophysics, University of Mumbai, Mumbai, Maharashtra, India.

Abstract

With the aim of developing early diagnostic/prognostic markers for oral cancer, desmosomal adhesion in sequentially progressive grades of tissues from oral normal/disorders (normal, hyperplastic, dysplastic, non-metastatic/metastatic tumours, and metastatic nodes) was investigated at protein and ultrastructural levels using immunohistochemistry and transmission electron microscopy, respectively. The expression of desmosomal proteins was higher in hyperplastic tissues than in normal tissues but was significantly decreased in subsequent progressive stages of the disease. Altered expression of desmosomal proteins was significantly correlated with local recurrence and disease-free survival. Ultrastructural analysis in the corresponding tissues revealed cytoplasmic clustering of desmosomes in hyperplasia; in more advanced disease stages, a significantly lower number of desmosomes and widened intercellular spaces were observed. Altered protein expression resulting in structural changes was confirmed by knocking down desmoplakin expression in non-transformed cells, which failed to form normal desmosome structures and induced a cell-transformation phenotype. Our data suggest that alterations in desmosomal assembly initiate at an early hyperplastic grade and, with more advanced disease stages, the severity of the alterations gradually becomes higher. Alterations in desmosomal adhesion can be useful for early detection of high-risk premalignant lesions, as well as for identification of invasive characteristics of primary non-metastatic tumours. Early detection will help to control further progression of disease by timely intervention.

KEYWORDS:

desmosomes; immunohistochemistry; oral leukoplakia; oral squamous cell carcinoma; transmission electron microscopy

PMID:
29905981
DOI:
10.1111/eos.12426
[Indexed for MEDLINE]

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