HER-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival

The original publication is available at the Annals website at www.springerlink.com/content/1534-4681.Background: HER-2/neu (c-erbB-2, HER2) gene amplification and protein overexpression have been associated with poor prognosis in several solid tumors, including breast and gastric cancer. Its incidence and significance in esophageal adenocarcinoma is unknown. Materials and Methods: Tissue microarrays were successfully constructed from 89 paraffin-embedded archival specimens of esophageal adenocarcinomas for HER2 gene amplification by silver-enhanced in situ hybridization (SISH). No patients had undergone neoadjuvant therapy. Protein overexpression was tested with immunohistochemistry (IHC) using automated immunostaining (Ventana Benchmark). Incidence of HER2 positivity, correlation to clinicopathological variables in esophageal cancer patients, and concordance between SISH and IHC were determined. Results: True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression. No significant associations were found among gene amplification and clinicopathological factors. The 5-year survival rates were 57% for esophageal cancer patients with HER2 amplification compared with 32% without, but the difference in overall survival was not significant (P = .37). The correlation between SISH and IHC was statistically significant (P < .0001). Conclusion: While molecular targeting may be possible for approximately 16% of esophageal adenocarcinoma patients, HER2 oncogene amplification did not influence survival in this study.Sarah K. Thompson, Thomas R. Sullivan, Ruth Davies and Andrew R. Ruszkiewic

Sentinel lymph node biopsy in esophageal cancer: Should it be standard of care?

IntroductionSentinel node mapping is established in some superficial cancers but remains controversial in harder-to-access solid tumors. There are an increasing number of recent studies suggesting that isolated tumor cells have prognostic significance in predicting poor survival, in breast cancer, esophageal cancer, and others. It is for this reason that we have persevered with the sentinel lymph node concept in our esophagectomy cancer patients, and we report our results since 2008.MethodsThirty-one of 32 consecutive patients underwent resection for invasive esophageal cancer along with sentinel lymph node retrieval (resection rate, 97%). Peritumoral injection of (99m)Tc antimony colloid was performed by upper endoscopy prior to the operation. A two-surgeon synchronous approach via a right thoracotomy and laparotomy was performed with a conservative lymphadenectomy. Sentinel lymph nodes were identified with a gamma probe both in and ex vivo, and sent off separately for three serial sections and immunohistochemistry with AE1/AE3.ResultsThe median patient age was 63.4 years (range, 45-75 years). Most patients (81%) had an adenocarcinoma, and 61% had received neoadjuvant therapy. At least one sentinel lymph node (median, 3) was identified in 29 of 31 patients (success rate, 94%). Sentinel nodes were present in more than one nodal station in 16 patients (55%). One false negative case led to a sensitivity of 90%. In 28 of 29 patients, the sentinel lymph node accurately predicted findings in non-sentinel nodes (accuracy, 96%).ConclusionsSentinel lymph node biopsy is both feasible and accurate in esophageal resections with conservative lymphadenectomy. It allows targeted serial sectioning and immunohistochemical studies of those nodes and should become standard of care in patients undergoing esophagectomy for esophageal cancer.Sarah K. Thompson, Dylan Bartholomeusz, Glyn G. Jamieso

Feasibility study of sentinel lymph node biopsy in esophageal cancer with conservative lymphadenectomy

IntroductionLymphoscintigraphy and sentinel node mapping is established in breast cancer and melanoma but not in esophageal cancer, even though many centers have shown that occult tumor deposits in lymph nodes influence prognosis. We report our initial experience with lymphoscintigraphy and sentinel lymph node biopsy in patients undergoing resection for esophageal cancer.MethodsSixteen of 17 consecutive patients underwent resection for invasive esophageal cancer along with sentinel lymph node retrieval (resection rate, 94%). Peritumoral injection of (99m)Tc antimony colloid was performed by upper endoscopy prior to the operation. A two-surgeon synchronous approach via right thoracotomy and laparotomy was performed with conservative lymphadenectomy. Sentinel lymph nodes were identified using a gamma probe both in vivo and ex vivo. Sentinel lymph nodes were sent off separately for serial sections and immunohistochemistry.ResultsMedian patient age was 60.4 years (range, 45-75 years). Fifteen were male, and thirteen had adenocarcinoma. At least one sentinel lymph node (median, 2) was identified in 14 of 16 patients (success rate, 88%). Sentinel nodes were present in more than one nodal station in five patients (31%). In all 14 patients, the sentinel lymph node accurately predicted findings in non-sentinel nodes (accuracy, 100%). Three patients with positive sentinel lymph nodes had metastases identified in non-sentinel nodes (sensitivity, 100%).ConclusionsSentinel lymph node biopsy is feasible in esophageal resection with conservative lymphadenectomy, and initial results suggest it is accurate in predicting overall nodal status. Further study is needed to assess impact on patient management and prognosis.Sarah K. Thompson, Dylan Bartholomeusz, Peter G. Devitt, Peter J. Lamb, Andrew R. Ruszkiewicz, Glyn G. Jamieso