Elebro Jacob, Heby Margareta, Gaber Alexander, Nodin Björn, Jonsson Liv, Fristedt Richard, Uhlén Mathias, Jirström Karin, Eberhard Jakob
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden.
Science for Life Laboratory, Royal Institute of Technology, 171 21, Stockholm, Sweden.
J Transl Med. 2014 Oct 17;12:289. doi: 10.1186/s12967-014-0289-8.
Pancreatic cancer and other pancreaticobiliary type periampullary adenocarcinomas have a dismal prognosis even after resection and neoadjuvant chemotherapy. Intestinal type periampullary adenocarcinomas generally have a better prognosis, but little is known on optimal neoadjuvant and adjuvant treatment. New prognostic and treatment predictive biomarkers are needed for improved treatment stratification of patients with both types of periampullary adenocarcinoma. Expression of the Special AT-rich sequence-binding protein 1 (SATB1) has been demonstrated to confer a worse prognosis in several tumour types, whereas its close homologue SATB2 is a proposed diagnostic and favourable prognostic marker for colorectal cancer. The prognostic value of SATB1 and SATB2 expression in periampullary adenocarcinoma has not yet been described.
Immunohistochemical expression of SATB1 and SATB2 was analysed in tissue microarrays with primary tumours and a subset of paired lymph node metastases from 175 patients operated with pancreaticoduodenectomy for periampullary adenocarcinoma. Kaplan-Meier and Cox regression analysis were applied to explore the impact of SATB1 and SATB2 expression on recurrence free survival (RFS) and overall survival (OS).
Positive expression of SATB1 was denoted in 16/106 primary pancreatobiliary type tumours and 11/65 metastases, and in 15/63 primary intestinal type tumours and 4/26 metastases, respectively. Expression of SATB1 was an independent predictor of a significantly shorter RFS and OS in pancreatobiliary type, but not in intestinal type adenocarcinomas. Moreover, SATB1 expression predicted an improved response to adjuvant chemotherapy in both tumour types. SATB2-expression was seen in 3/107 pancreatobiliary type primary tumours, and in 8/61 intestinal type primary tumours. The small number of cases with positive SATB2 expression did not allow for any firm conclusions on its prognostic value.
These findings demonstrate the potential utility of SATB1 as a prognostic and predictive biomarker for chemotherapy response in both intestinal type and pancreatobiliary type periampullary adenocarcinomas, including pancreatic cancer.
胰腺癌及其他胰胆管型壶腹周围腺癌即便在切除及新辅助化疗后预后仍较差。肠型壶腹周围腺癌总体预后较好，但关于最佳新辅助及辅助治疗知之甚少。需要新的预后及治疗预测生物标志物以改善这两种类型壶腹周围腺癌患者的治疗分层。特殊富含AT序列结合蛋白1（SATB1）的表达已被证明在几种肿瘤类型中预示预后较差，而其紧密同源物SATB2被认为是结直肠癌的诊断及良好预后标志物。SATB1和SATB2表达在壶腹周围腺癌中的预后价值尚未见报道。
在组织芯片中分析了175例行胰十二指肠切除术治疗壶腹周围腺癌患者的原发性肿瘤及配对淋巴结转移灶亚组中SATB1和SATB2的免疫组化表达。应用Kaplan-Meier和Cox回归分析探讨SATB1和SATB2表达对无复发生存期（RFS）和总生存期（OS）的影响。
SATB1在106例原发性胰胆管型肿瘤中的16例及转移灶中的11例呈阳性表达，在63例原发性肠型肿瘤中的15例及转移灶中的4例呈阳性表达。SATB1表达是胰胆管型腺癌RFS和OS显著缩短的独立预测因素，但在肠型腺癌中不是。此外，SATB1表达预示两种肿瘤类型对辅助化疗的反应均有所改善。SATB2在107例胰胆管型原发性肿瘤中的3例及61例肠型原发性肿瘤中的8例有表达。SATB2阳性表达病例数较少，无法就其预后价值得出任何确切结论。
这些发现表明SATB1作为肠型和胰胆管型壶腹周围腺癌（包括胰腺癌）化疗反应的预后及预测生物标志物具有潜在应用价值。
