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VEGF-C AND CXCR4 EXPRESSION IN ESOPHAGEAL CANCER : CASE SERIES AND META-REVIEW OF THE LITERATURE
JK Law, L Zypchen, BI Dalal, DA Owen, IT Tai
Esophageal cancer is a highly aggressive tumour with poor prognosis. Few patients are felt to be surgical candidates at the time of diagnosis because of the presence of distant metastases and/or locally unresectable tumour growth. Identification of patients with potentially curable disease relies upon staging modalities such as computed tomography (CT), endoscopic ultrasound (EUS) and position emission tomography (PET).
Metastases is the result of several sequential steps and is a preprogrammed phenomenon. The expression of vascular endothelial growth factor (VEGF) has been implicated in nodal metastases through its tumour lymphoangiogenic effect. VEGF expression in esophagectomy specimens has been shown to correlate with lymph node metastases, TMN stage and depth of invasion in squamous cell esophageal cancer but not consistently in adenocarcinoma. Serum VEGF has also been found to be increased in patients with N1 squamous cell esophageal cancer. Another marker of metastatic disease is the chemokines, chemotactic factors involved in the regulation of the development and migration of various cell types. CXCR4 expression has had inconsistent expression in esophagectomy specimens for both histologic types of esophageal cancer but when present, is associated with poorer clinical outcomes. Presence of tumour cells in patients with micrometastases can also be detected on bone marrow biopsy by flow cytometry and immunohistochemistry for cytokeratin positive tumour cells.
We present 2 cases of highly aggressive esophageal adenocarcinoma in which both patients underwent bone marrow biopsies for other indications. In both cases, patients underwent endoscopic evaluation of the esophagus and biopsies of nodules in the distal esophagus confirmed the diagnosis of esophageal adenocarcrinoma. In both esophageal specimens, stains for CXCR4 were positive but negative for VEGF. In the bone marrow biopsies, both patients were highly positive for cytokeratin and CXCR4 but negative for VEGF. CT scan evaluation of each patient did not reveal any evidence of metastatic or infiltrative disease.
While currently not standard, patients with a diagnosis for esophageal cancer should be considered for bone marrow biopsy as part of routine staging and also for consideration for directed chemotherapy.