Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

BACKGROUND: To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies. METHODS: The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up. RESULTS: Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor. CONCLUSION: Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Direct Genetic Analysis of Single Disseminated Cancer Cells for Prediction of Outcome and Therapy Selection in Esophageal Cancer

SummaryThe increasing use of primary tumors as surrogate markers for prognosis and therapeutic decisions neglects evolutionary aspects of cancer progression. To address this problem, we studied the precursor cells of metastases directly for the identification of prognostic and therapeutic markers and prospectively analyzed single disseminated cancer cells from lymph nodes and bone marrow of 107 consecutive esophageal cancer patients. Whole-genome screening revealed that primary tumors and lymphatically and hematogenously disseminated cancer cells diverged for most genetic aberrations. However, we identified chromosome 17q12–21, the region comprising HER2, as the most frequent gain in disseminated tumor cells that were isolated from both ectopic sites. Survival analysis demonstrated that HER2 gain in a single disseminated tumor cell but not in primary tumors conferred high risk for early death