Background: Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates.

The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.

During the last few years, there has been a gradual increase in treatment options for patients with esophageal malignancies. Several clinical studies have been performed, covering not only radiation and chemotherapy, but also the introduction of novel biological agents into the treatment arsenal. Patients with esophageal carcinoma are now offered second-line and sometimes even third-line treatments, and the number of research protocols is increasing. Despite the newly awakened interest in this malignancy, the overall 5-year survival rate has remained at approximately 10% since the 1980s. This review contains a compilation of available studies of esophageal malignancies and discusses current treatment options as well as newly developed therapies targeted at growth factor receptors.

Angiogenesis is the formation of new blood vessels out of the existing vascular bed. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are potent circulating angiogenic factors, whereas cystatin C is one of the most important extracellular inhibitors of several cysteine proteinases. Because proteases degrade interstitial connective tissue and basement membranes during tumor growth and metastasis, an association between cystatin C and the angiogenic factors seems plausible. The primary aim of the present study was to investigate if such a correlation exists between these serum markers. The secondary aim was to determine the prognostic value of these circulating cytokines and cystatin C, collected prior to therapy, in patients with esophageal carcinoma.A total of 42 patients with esophageal carcinoma donated serum samples prior to therapy. VEGF and bFGF were correlated to platelet and leukocyte counts and VEGF was correlated to tumor volume (p = 0.04), whereas bFGF was not (p = 0.08). VEGF was significantly correlated with cystatin C (p = 0.027). Survival analysis showed that VEGF regarded as a continuous variable was associated with a significantly poorer survival in the univariate analysis (p = 0.023); however, this was not found for bFGF (p = 0.46). Neither of the angiogenic factors were associated with survival in the multivariate analysis. In the univariate analysis, cystatin c was correlated with survival (p = 0.01), but this was not found in the multivariate analysis (p = 0.28). In conclusion, VEGF was correlated with cystatin C, possible explanations being discussed in the present article. Results of the present study indicate that use of the angiogenic factors as prognostic factors, prior to therapy in patients with esophageal carcinoma, appears limited.

Esophageal carcinoma is the seventh most common cause of cancer-related death in the Western world. In Sweden, approximately 400 new esophageal carcinomas are diagnosed yearly. Cytokeratins (CK) are specific for epithelial cells and the expression profile usually remains unchanged even when the epithelium undergoes malignant transformation. In the present study, MonoTotal, a newly developed RIA-assay detecting circulating CK 8, 18 and 19 fragments, was investigated in sera from patients with esophageal carcinoma. Serum samples from 40 patients with esophageal carcinoma were collected. The median value of circulating CK 8, 18 and 19 measured with MonoTotal was 378 U/L (range 53-6843) and with regard to the defined cut-off (< 75 U/L), 39/40 (98%) patients were shown to have elevated levels of circulating CK 8, 18 and 19. Patients with localized disease had a median value of circulating CK 8, 18 and 19 of 305 U/L (mean: 500 U/L), whereas the corresponding value for metastatic disease was 771 U/L (mean: 1506 U/L). This difference was statistically significant (P = 0.016). Circulating CK 8, 18 and 19, according to cut-off, were not associated with survival in univariate analysis (P = 0.34). However, continuous values of circulating levels of CK 8, 18 and 19 were associated with survival (P = 0.000083) in univariate as well as in the multivariate analysis (P = 0.03). In conclusion, circulating CK 8, 18 and 19 correlates with increased tumor burden and might, in conjunction with other clinical parameters, aid the clinician in estimating the prognosis of the individual patient.