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Molecular Oncology, Markers, Clinical Correlates |
Departments of Surgery [T. E. G., S. R., L. A. K., J. D. L.], Human Genetics [T. E. G.], Pathology [S. D. F.], and Biostatistics [W. E. G.] and the University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213
Purpose: In esophageal cancer, lymph node metastases are the strongest predictor of recurrence and poor outcome. However, many node-negative patients still recur despite a potentially curative resection. This is probably the result of microscopically occult metastases missed by histological examination. In this study, we used both standard, gel-based reverse transcription-PCR (RT-PCR) and Taqman quantitative RT-PCR (QRT-PCR) for carcinoembryonic antigen (CEA) mRNA to detect occult micrometastases in 387 lymph nodes from 30 histologically node-negative esophageal cancer patients.
Experimental Design: CEA expression was compared with clinical outcomes to determine correlation with disease recurrence. For quantitative data, an optimum CEA expression level cutoff value was defined as the value that most accurately classified patients on the basis of disease recurrence. Kaplan-Meier survival curves were generated, and multivariate analyses were performed to evaluate the prognostic value of QRT-PCR.
Results: CEA expression levels were above the optimum cutoff level in 12 tissue blocks, resulting in the identification of 11 CEA-positive patients. Of these patients, 9 suffered disease recurrence and 2 remain disease free. Of the 19 CEA-negative patients, there was 1 disease recurrence. The sensitivity and specificity for predicting disease recurrence were 90 and 90%, respectively. Kaplan-Meier analysis showed that CEA positivity resulted in significantly lower disease-free and overall survival (P <0.0001 and 0.0006 respectively). In multivariate analyses, CEA positivity measured by QRT-PCR was the strongest independent predictor of disease recurrence among other clinical and pathological factors examined.
Conclusions: QRT-PCR offers significant benefits over standard RT-PCR and identifies node-negative patients at high risk for recurrence.
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