Gains and losses of adhesion molecules (CD44, E-cadherin, and beta-catenin) during oral carcinogenesis and tumour progression.
The aim of this study was to define whether or not the impaired expression of CD44, E-cadherin (E-cad), and beta-catenin (beta-cat) correlates with the clinical evolution and prognosis of oral cancer. Ninety-three primary oral squamous cell carcinomas (OSCCs) with tumour-adjacent normal and/or dysplastic mucosa, 30 associated metastases, and 12 recurrences were immunostained for CD44s, -v3, -v4, -v5, -v6, -v7, -v9, E-cad, and beta-cat. In non-neoplastic epithelium, all molecules investigated were constitutively expressed in the basal layers. In the majority of dysplasias, immunoreactivity for all adhesion molecules was increased, but there was restricted loss for CD44s, E-cad, and beta-cat in a few cases. In carcinomas, a striking accumulation of CD44s, v3, v4, v9 and a loss of E-cad/beta-cat were observed at the invasive tumour front. In metastases and recurrences, besides a loss of CD44s, v4, v7, and E-cad, a significant increase of v9 was recorded, whereas CD44v5 and v6 remained unchanged. Clinically, reduced expression of CD44v3, E-cad, and changes of CD44v9 phenotype within the primary tumours correlated significantly with poor prognosis; decreased beta-cat expression was a predictive marker for nodal metastases. These findings indicate that there is some perturbed expression of adhesion molecules during the stepwise course of oral carcinogenesis and tumour progression. Distinct phenotypic alterations project poor prognosis, while others predict metastasis. Some of these restricted molecular changes may serve as potential targets for future antibody-based tumour therapy.
Bánkfalvi
Agnes
A
Domagk-Institute of Pathology, Wilhelms-University, Münster, Germany. bankfal@uni-muenster.de
Krassort
Melanie
M
Buchwalow
Igor B
IB
Végh
Andras
A
Felszeghy
Endre
E
Piffkó
Jozsef
J
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin