Elsevier

Oral Oncology

Volume 44, Issue 1, January 2008, Pages 72-77
Oral Oncology

EpCAM expression in squamous cell carcinoma of the oral cavity: Frequency and relationship to clinicopathologic features

https://doi.org/10.1016/j.oraloncology.2007.01.008Get rights and content

Summary

This retrospective study was designed to investigate the prognostic significance of EpCAM expression in human oral squamous cell carcinoma on a long-term follow-up. EpCAM expression was examined immunohistochemically on a tissue microarray (TMA) of paraffin embedded tissue specimens from 77 consecutive patients who underwent surgical treatment for squamous cell carcinoma of the oral cavity in the period between 1980 and 1997 at the Department of Craniomaxillofacial and Oral Surgery, Innsbruck Medical University. High EpCAM expression was found in 17 (22.1%) of the tumor samples. Using Kaplan-Meier analysis no correlation of EpCAM overexpression was observed with conventional clinicopathologic features in this patient cohort. Taken together, these data suggest that EpCAM might become an attractive treatment target in a subgroup of patients with OSCC.

Introduction

Squamous cell carcinoma of the oral cavity (OSCC), a subgroup of head and neck cancers, accounts world wide for about 4% of all carcinomas in men and 2% in women, with a varying geographical frequency. This tumor entity represents more than 95% of all malignant neoplasms in the oral cavity.1 A high incidence of oral squamous cell carcinoma is present in India.2 Chronic consumption of tobacco as well as betel nut in combination with alcohol abuse have been described to be essential risk factors for pathogenesis of this entity.3 Alcohol favours higher permeability of the oral mucosa, which in turn enhances the carcinogenic effects of nitrosamines and polycyclic hydrogen contained in tobacco. Insufficient oral hygiene, chronic pressure caused by dental prostheses, infection by papilloma virus types 16 and 18, chronic exposure to sunlight (particularly ultraviolet light) and chronic diseases (such as Plummer–Vinson-syndrome or Lichen planus) have been reported to be further possible etiologic factors.4 The mortality rate from OSCC has not changed significantly during the past 30 y5 and a median overall 5 y survival rate of less then 50% remains unsatisfactory.6 This is attributed largely to the fact that most patients with OSCC present in an advanced tumor stage. Tumors spread into the adjacent regions and the therapeutic interventions may detract from the patients aesthetic appearance. At present, therapeutic decisions are based on clinical-pathological parameters, including age, TNM stage and histological grade. Although useful, these factors often fail to differentiate between more or less aggressive tumor types. The prognosis of oral squamous cell carcinoma is based on clinical stage (according to TNM classification) and tumor grading.7 Over the past years, various strategies adding chemotherapy to radiotherapy have been developed to improve treatment outcome.8 Cisplatin and 5-FU based chemotherapy regimens are effective in patients with advanced OSCC and appear to improve survival of patients who have a good response.9

EpCAM (also called GA733-2) a calcium-independent homophilic cell adhesion molecule with an apparent molecular weight of 39–42 kDa10, 11 is expressed by the majority of epithelial tissues. The EpCAM antigen does not belong to the major families of adhesion molecules such as cadherins, selectins or integrins, but is a type I transmembrane glycoprotein, consisting of an extracellular domain and a shorter cytoplasmic domain of 26 amino acids (for review see, Balzar et al.12). The gene was mapped to human chromosome 2.13, 14

EpCAM is also abundantly expressed in a subset of human carcinomas of different origins. Increasing EpCAM expression was found to be associated with a higher proliferation rate and tumor progression.15, 16 Our group found 35–42% of patients with invasive breast carcinoma to overexpress EpCAM by semiquantitative immunohistochemistry. In breast cancer EpCAM overexpression represents a strong predictor of poor disease-free and overall survival.17, 18, 19 A similar correlation was seen in patients suffering from gallbladder carcinoma.20 Notably, in vitro data suggest that EpCAM expression is not merely a prognostic marker but can directly enhance the malignant phenotype.21, 22

Based on these findings, EpCAM has attracted major interest as a target for passive and active immunotherapy. In fact, anti-tumor responses have originally been observed in metastatic colorectal cancer following treatment with the EpCAM specific monoclonal antibody edrecolomab.23, 24 New EpCAM specific humanized antibodies (such as MT201) and vaccines are currently being tested in clinical trials.

No data on EpCAM expression and its relationship to conventional clinicopathologic features in OSCC have been observed so far. We therefore retrospectively investigated the frequency and prognostic value of EpCAM expression in squamous cell carcinoma of the oral cavity.

Section snippets

Patients

This retrospective study was conducted according to the regulations of the local ethics committee and Austrian Law. Demographic data and tumor characteristics are summarized in Table 1. All patients underwent surgery at the Department of Cranio, Maxillofacial and Oral Surgery, Innsbruck Medical University. Between 1980 and 1997 a total of 77 consecutive patients for whom tissue specimens from the local pathology repository as well as clinical follow-up data were available could be included into

Discussion

The EpCAM antigen has recently attracted interest as a potential therapeutic target. Antigen specific therapeutic targeting strategies are an important and growing field of oral pathology. We have summarized the expression of different antigens in Table 3. The prognostic role of EpCAM expression has been extensively studied by our group in malignancies of epithelial origin such as breast cancer,19 gallbladder cancer,20 ovarian cancer25 and pancreatic cancer.26 However, although the expression

References (39)

  • T. Sasaki et al.

    Clinico-pathological features of squamous cell carcinoma of the oral cavity in patients <40 years of age

    J Oral Pathol Med

    (2005)
  • J.J. Sciubba

    Oral cancer. The importance of early diagnosis and treatment

    Am J Clin Dermatol

    (2001)
  • S.V. Litvinov et al.

    Evidence for a role of the epithelial glycoprotein 40 (Ep-CAM) in epithelial cell–cell adhesion

    Cell Adhes Commun

    (1994)
  • S.V. Litvinov et al.

    Ep-CAM: a human epithelial antigen is a homophilic cell–cell adhesion molecule

    J Cell Biol

    (1994)
  • M. Balzar et al.

    The biology of the 17-1A antigen (Ep-CAM)

    J Mol Med

    (1999)
  • N.K. Spurr et al.

    Characterization and chromosomal assignment of a human cell surface antigen defined by the monoclonal antibody AUAI

    Int J Cancer

    (1986)
  • G. Calabrese et al.

    Assignment of TACSTD1 (alias TROP1, M4S1) to human chromosome 2p21 and refinement of mapping of TACSTD2 (alias TROP2, M1S1) to human chromosome 1p32 by in situ hybridization

    Cytogenet Cell Genet

    (2001)
  • S.V. Litvinov et al.

    Expression of Ep-CAM in cervical squamous epithelia correlates with an increased proliferation and the disappearance of markers for terminal differentiation

    Am J Pathol

    (1996)
  • G. Spizzo et al.

    Prognostic significance of Ep-CAM AND Her-2/neu overexpression in invasive breast cancer

    Int J Cancer

    (2002)
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    • The involvement of promoter methylation and DNA methyltransferase-1 in the regulation of EpCAM expression in oral squamous cell carcinoma

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      In contrast, other studies suggested that EpCAM could have a tumor suppressor effect in some malignancies.5–7 Previously, the expression of EpCAM and its clinical significance in OSCC was studied.8–10 However, the results were not consistent.

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