Kyriazanos Ioannis D, Tachibana Mitsuo, Dhar Dipok K, Shibakita Muneaki, Ono Takashi, Kohno Hitoshi, Nagasue Naofumi
Shimane Medical University, Second Department of Surgery, Izumo, Shimane 693-8501, Japan.
Oncol Rep. 2002 May-Jun;9(3):503-10.
The purpose of this study was to evaluate the expression of S100A2 Ca2+-binding protein and its prognostic significance in the management of squamous cell carcinoma of the esophagus. Changes in cytosolic Ca2+ concentration control a wide range of cellular responses including cellular apoptosis. Intracellular S100 Ca2+-binding proteins are key molecules in transducing Ca2+ signaling. Among these, S100A2 has recently attracted major interest due to its stable expression in normal epithelia and down-regulation in some tumors. As a candidate tumor suppressor, expression of S100A2 has been proposed as a valuable prognostic marker in different tumors. We examined the clinical significance of S100A2 expression in 116 resected specimens of esophageal squamous cell carcinomas (ESCC) using immunohistochemistry. S100A2 was positive in 49 cases (42.2%) and its expression was significantly higher in large (p=0.01) and well differentiated tumors (p=0.013). Lymph node-positive tumors had a lower expression of S100A2 protein in comparison to the corresponding lymph node negative equivalents in each of the T stages, but the difference was statistically significant (p=0.041) only for the T1b tumors. S100A2 status became an independent predictor of patient survival (p=0.026) in lymph node-negative cases but not in node-positive cases. Evaluation of S100A2 protein expression may play an important role in the management of ESCC. The node-negative ESCC patients without S100A2 expression might be a high-risk group with poor survival and will need further attention to design appropriate adjuvant therapy.
本研究旨在评估S100A2钙结合蛋白在食管鳞状细胞癌治疗中的表达及其预后意义。胞质钙浓度的变化控制着包括细胞凋亡在内的广泛细胞反应。细胞内S100钙结合蛋白是转导钙信号的关键分子。其中,S100A2因其在正常上皮中的稳定表达以及在某些肿瘤中的下调,最近引起了人们的极大关注。作为一种候选肿瘤抑制因子,S100A2的表达已被提议作为不同肿瘤中有价值的预后标志物。我们采用免疫组织化学方法检测了116例食管鳞状细胞癌(ESCC)切除标本中S100A2表达的临床意义。49例(42.2%)S100A2呈阳性,其在大肿瘤(p=0.01)和高分化肿瘤(p=0.013)中的表达明显更高。与各T分期中相应的淋巴结阴性肿瘤相比,淋巴结阳性肿瘤中S100A2蛋白表达较低,但仅在T1b肿瘤中差异具有统计学意义(p=0.041)。在淋巴结阴性病例中,S100A2状态成为患者生存的独立预测因素(p=0.026),而在淋巴结阳性病例中则不然。评估S100A2蛋白表达可能在ESCC的治疗中发挥重要作用。无S100A2表达的淋巴结阴性ESCC患者可能是生存较差的高危人群,需要进一步关注以设计合适的辅助治疗。