Early evaluation of the apoptotic index ratio is useful in predicting the efficacy of chemoradiotherapy in esophageal squamous cell carcinoma

Abstract

Abstract. Chemoradiotherapy for advanced esophageal cancer is a standard treatment alongside surgical treatment. Although numerous investigators have attempted to identify the predictive markers for chemoradiosensitivity, there appear to be few candidates that can be applied in clinical use. Using biopsy specimens, we investigated the apoptotic index (AI) prior to treatment and following a radiation dose of 10 Gy to detect the early response to chemoradiotherapy in 28 patients with esophageal squamous cell carcinoma. Molecular markers, including p53, p21, bax, bcl-2, HSP27, HSP70, HSP90, Ku70, Ku86 and HIF-1α, were also examined by immunohistochemical staining. The patients were divided into two groups depending on the response to chemoradiotherapy: a responder group (RG) (n=19) that included the patients with complete or partial response, and a non-responder group (NRG) (n=9), that included patients with stable or progressive disease. In the RG and NRG, the AI of pretreatment was 4.7±5.3 (mean ± SD, cells/1,000 cells) and 5.9±3.7, respectively. The apoptotic index ratio (AIR), which was determined by dividing the AI following 10 Gy radiation by the pretreatment AI, was higher in the RG compared to the NRG (4.7±4.5 versus 1.9±1.4, p=0.03). When the cut-off value of AIR was set at 2.4, the sensitivity, specificity and accuracy were 74, 78 and 76%, respectively. Among the molecular markers we examined immunohistochemically, a positive p53 expression in the pretreatment evaluation was associated with the efficacy of chemoradiotherapy (p=0.08). Regarding the expression of other molecular markers, no significant correlations were found in RG and NRG. In the present study, the results indicated that AIR is useful for the prediction of chemoradiosensitivity in esophageal squamous cell carcinoma.

Radio-responsive tumors exhibit greater intratumoral immune activity than nonresponsive tumors

“…As a result, much emphasis has been devoted to understanding the responder/non-responder phenomena in the hope of skewing the ratio in favor of responders. The majority of the work addressing this issue focuses on predictive factors present in tumors before treatment 2, 4-6 . Consequently, a list of genes that may discriminate responders versus non-responders has been identified and includes genes associated with cell cycle, apoptosis, DNA repair, and survival 2, 3, 5-7 .…”

“…2,[4][5][6] Consequently, a list of genes that may discriminate responders versus nonresponders has been identified and includes genes associated with cell cycle, apoptosis, DNA repair and survival. 2,3,[5][6][7] However, little work has addressed whether changes occur directly within responder or nonresponder tumors shortly after RT, and if these modifications correlate with outcome. In other words, what is lacking is a thorough understanding of the mechanism that governs either a positive or negative outcome in response to radiotherapy.…”