Immunocytochemical detection of circulating esophageal carcinoma cells by immunomagnetic separation

Background: Recent developments in detection of micrometastasis have reveal ed a considerable incidence of systemic disease in patients who would previ ously have been diagnosed as having solid rumours only. The purpose of this study was to investigate the prevalence and clinical significance of circu lating carcinoma cells in patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: Peripheral blood samples from 47 primary ESC C patients were enriched by immunomagnetic separation (IMS) using Ber-EP4-c onjugated beads (Dynabeads anti-epithelial cell) and immunostained with an anti-cytokeratin (anti-CK) antibody. We assayed samples from 12 patients to compare the detection of CK-reactive cells using IMS with the detection of CK 19 mRNA using a reverse transcriptase-polymerase chain reaction (RT-PCR ) method Results: CK-reactive cells were observed in 18 out of 47 patients (38%). The detection rate was closely correlated with the stage of disease (TNM stage) (p = 0.0017). In 33 patients who underwent esophagectomy, 4 out of 7 patients (57%) positive for CK cells and only 2 out of 26 patients (7 .7%) negative suffered from recurrence in the distant lymph nodes or lungs (p = 0.0108). When IMS and RT-PCR were compared, am 3 samples that were CK- positive by IMS had CK 19 mRNA detected by RT-PCR. However, the other 4 sam ples with CK 19 mRNA by RT-PCR were negative for CK cells by IMS. Of 7 pati ents positive for CK-reactive cells before chemotherapy or chemoradiotherap y, 4 patients negative after treatment survived bur 3 patients who remained positive died within 6 months. Conclusion: Immunocytochemical detection of circulating carcinoma cells by IMS may be a specific method for the diagno sis of systemic disease and for monitoring treatment response.