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PR01.01 Evaluation of Circulating Tumor Cells for Non-Invasively Discerning Lung Primary from Metastasis

      Background

      Lungs are the most common site of primary malignancy as well as metastasis from primary malignancies in other organs. Radiological imaging scans often present a diagnostic conundrum where suspicious lesions are observed in various organs including the lungs thus necessitating an invasive biopsy for histopathological diagnosis which remains the standard for diagnosis and disambiguation of primary lung malignancy and metastatic deposit. We present a non-invasive means for discerning primary lung malignancy from metastatic deposit based on Immunocytochemistry (ICC) profiling of Circulating Tumor Cells (CTCs) from peripheral blood.

      Methods

      We collected peripheral blood from 229 individuals with suspicious findings on radiological scans involving the lung and various other organs such as the liver, chest wall, colon, hepatobiliary tract or the gastroesophageal tract. Patients underwent an invasive biopsy of the lungs to obtain tumor tissue for histopathological examination (HPE) which were initially blinded. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and treated with an epigenetically activating medium which induces cell death in normal (non-malignant) hematolymphoid cells as well as epithelial cells in peripheral blood, but selectively confers survival privilege on apoptosis resistant tumor-derived Circulating Tumor Cells (CTCs). CTCs were profiled by ICC using IVD approved antibodies against organ and subtype specific (OSS) antigens to determine the tissue of origin (TOO). ICC findings were compared with the HPE results to determine concordance.

      Results

      Among the 229 individuals, 10 each were diagnosed with a primary malignancy of the breast, colon and lungs, 5 each of esophagus and stomach, 4 of liver and 3 of pancreas. ICC profiling of CTCs for OSS antigens indicated a 96.9% overall concordance with HPE findings. ICC profiling of CTCs accurately discerned primary malignancies of the lungs, colon, esophagus, pancreas and stomach with 100% accuracy, of the breast with 90% accuracy and of the liver with 75% accuracy.

      Conclusion

      The findings suggest that ICC profiling of CTCs can non-invasively discern primary malignancy of the lungs from metastatic deposits in the lungs with high accuracy. In the clinical setting, this approach will be useful for diagnostic triaging in individuals with confounding radiological findings, especially where a biopsy of the lungs (or any other organ) is not possible owing to anatomical considerations or patient’s co-morbidities.