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The expression of Ep-CAM (17-1A) in squamous cell cancers of the lung
C J Piyathilake1, A R Frost, H Weiss
1Department of Nutrition Sciences, Comprehensive Cancer Center of the University of Alabama at Birmingham, 35294, USA.
Abstract:
Immunotherapy trials using monoclonal antibodies 323/A3 and 17-1A that recognize Ep-CAM, including trials focused on cancer of the lung, currently are underway. Nevertheless, there have been few comprehensive evaluations of the expression of Ep-CAM in specific types of neoplastic processes, including cancer of the lung. The current study of 60 human subjects with squamous cell cancer (SCC) of the lung, selected at random, was undertaken (1) to examine the expression of Ep-CAM in SCC and associated uninvolved bronchial mucosa, bronchial epithelial hyperplasia, and dysplasia, and (2) to correlate the results with established prognostic indicators and survival of patients. In both the uninvolved bronchial mucosa and epithelial hyperplasia, the expression of Ep-CAM in luminal cells was significantly higher compared with its expression in the matched basal cells (P = .003, P < .0001, respectively). When Ep-CAM scores of basal and luminal cells present in uninvolved bronchial mucosa and epithelial hyperplasia were combined, we observed a statistically significant stepwise increase in Ep-CAM expression from uninvolved bronchial mucosa to epithelial hyperplasia to SCC, suggesting its involvement in malignant transformation of SCC. The expression of Ep-CAM was significantly higher in poorly to moderately differentiated SCC compared with well-differentiated SCC (P = .04). An increase in the expression of Ep-CAM with increasing size or local extent of the primary tumor approached statistical significance (P = .09). The expression of Ep-CAM increased significantly with increasing involvement of regional lymph nodes (P = .02). Similarly, the expression of Ep-CAM increased with the increasing TNM stages (P = .04). Kaplan-Meier Survival analysis using the same categorizations showed that increasing tumor size, nodal status, and stage were significantly associated with poor patient survival (P = .04, .01, .01, respectively). There was, however, no statistically significant association between patient survival and staining intensity of carcinomas for Ep-CAM. We conclude that expression of Ep-CAM increased during the progression of SCC of the lung and, therefore, may play a role in the carcinogenesis of this disease.
Insights
EpCAM expression increases during lung squamous cell cancer progression. This biomarker
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Immunotherapy targeting EpCAM (Epithelial Cell Adhesion Molecule) is under investigation for lung cancer.
- Comprehensive evaluations of EpCAM expression in lung cancer subtypes are limited.
- Understanding EpCAM's role in lung squamous cell carcinoma (SCC) progression is crucial.
Purpose of the Study:
- To evaluate EpCAM expression in lung SCC, adjacent normal tissues, hyperplasia, and dysplasia.
- To correlate EpCAM expression with prognostic indicators and patient survival in lung SCC.
Main Methods:
- Analysis of EpCAM expression in 60 randomly selected lung SCC patients.
- Comparison of EpCAM levels in tumor cells, uninvolved bronchial mucosa, and pre-neoplastic lesions.
- Correlation with tumor size, lymph node involvement, TNM stage, and patient survival.
Main Results:
- EpCAM expression significantly increased from uninvolved mucosa to hyperplasia to SCC.
- Higher EpCAM levels were observed in poorly to moderately differentiated SCC compared to well-differentiated SCC.
- Increased EpCAM expression correlated significantly with lymph node involvement and advanced TNM stage.
Conclusions:
- EpCAM expression rises during the progression of lung squamous cell carcinoma.
- EpCAM may play a role in the carcinogenesis of lung SCC.
- While EpCAM expression correlates with disease progression, it did not directly predict patient survival in this study.