Targets for molecular therapy in esophageal squamous cell carcinoma: an immunohistochemical analysis

Neoadjuvant chemotherapy may improve the outcome of esophageal cancer after esophagectomy, but is accompanied by considerable toxicity by collateral destruction of normal cells. Such side effects may be avoided by developing therapies that specifically target molecular characteristics of tumors. The aim of the present study was to determine the proportion of esophageal squamous cell carcinoma (ESCC) patients that could possibly benefit from (a combination of) currently available targeted therapies, by assessing the frequency of immunohistochemical expression of their target molecular markers in ESCC tissues. Sections from a validated tissue microarray comprising 108 ESCCs were immunohistochemically stained for Bcl-2, c-KIT, cyclo-oxygenase-2 (COX-2), cyclin D1, estrogen receptor (ER), epidermal growth factor receptor (EGFR), Her-2/neu, progesterone receptor (PR), and vascular endothelial growth factor (VEGF). VEGF, cyclin D1, EGFR, and COX-2 could be detected in 55, 42, 40, and 40%, respectively. Her-2/neu, Bcl-2, and c-KIT were detected in 12, 11, and 10% of the tumors, respectively. No nuclear expression of ER or PR was noticed. Concurrent expression of two markers was noticed in 28% of ESCCs, whereas 25% of ESCCs showed concurrent expression of three markers. The concurrent expression of two of the most frequently expressed markers (VEGF, cyclin D1, EGFR, and COX-2) ranged from 11 (COX-2 and EGFR) to 26% (cyclin D1 and VEGF). The expression of all of these four markers was seen in 5% of ESCCs. Promising targets for molecular therapy in ESCC appear to be COX-2, VEGF, EGFR, and cyclin D1, as they are frequently overexpressed. Phase II clinical studies on these molecular markers may therefore be warranted. The role for targeted therapy against ER, PR, Her-2/neu, c-KIT, or Bcl-2 in ESCC seems limited.