期刊论文详细信息
Journal of Translational Medicine
Prognostic and treatment predictive significance of SATB1 and SATB2 expression in pancreatic and periampullary adenocarcinoma
Jakob Eberhard1  Karin Jirström1  Mathias Uhlén2  Richard Fristedt1  Liv Jonsson1  Björn Nodin1  Alexander Gaber1  Margareta Heby1  Jacob Elebro1 
[1] Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skåne University Hospital, Lund, 221 85, Sweden;School of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm, 106 91, Sweden
关键词: Treatment prediction;    Prognosis;    Biomarkers;    Immunohistochemistry;    Pancreatic cancer;    Periampullary adenocarcinoma;   
Others  :  1147527
DOI  :  10.1186/s12967-014-0289-8
 received in 2014-08-04, accepted in 2014-10-05,  发布年份 2014
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【 摘 要 】

Background

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.

Methods

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).

Results

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.

Conclusions

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.

【 授权许可】

   
2014 Elebro et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Romiti A, Barucca V, Zullo A, Sarcina I, Di Rocco R, D'Antonio C, Latorre M, Marchetti P: Tumors of ampulla of Vater: A case series and review of chemotherapy options. World J Gastrointest Oncol 2012, 4:60-67.
  • [2]Westgaard A, Pomianowska E, Clausen OP, Gladhaug IP: Intestinal-type and pancreatobiliary-type adenocarcinomas: how does ampullary carcinoma differ from other periampullary malignancies? Ann Surg Oncol 2013, 20:430-439.
  • [3]Han HJ, Russo J, Kohwi Y, Kohwi-Shigematsu T: SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 2008, 452:187-193.
  • [4]Dobreva G, Dambacher J, Grosschedl R: SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression. Genes Dev 2003, 17:3048-3061.
  • [5]Kohwi-Shigematsu T, Poterlowicz K, Ordinario E, Han HJ, Botchkarev VA, Kohwi Y: Genome organizing function of SATB1 in tumor progression. Semin Cancer Biol 2013, 23:72-79.
  • [6]Mao L, Yang C, Wang J, Li W, Wen R, Chen J, Zheng J: SATB1 is overexpressed in metastatic prostate cancer and promotes prostate cancer cell growth and invasion. J Transl Med 2013, 11:111. BioMed Central Full Text
  • [7]Zhao XD, Ji WY, Zhang W, He LX, Yang J, Liang HJ, Wang LL: Overexpression of SATB1 in laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec 2010, 72:1-5.
  • [8]Shen Z, Zeng Y, Guo J, Wu Y, Jiang X, Ding R, Wu C, Li R, Luo B, Zeng C, Jiang H, Jie W: Over-expression of the special AT rich sequence binding protein 1 (SATB1) promotes the progression of nasopharyngeal carcinoma: association with EBV LMP-1 expression. J Transl Med 2013, 11:217. BioMed Central Full Text
  • [9]Tu W, Luo M, Wang Z, Yan W, Xia Y, Deng H, He J, Han P, Tian D: Upregulation of SATB1 promotes tumor growth and metastasis in liver cancer. Liver Int 2012, 32:1064-1078.
  • [10]Meng WJ, Yan H, Zhou B, Zhang W, Kong XH, Wang R, Zhan L, Li Y, Zhou ZG, Sun XF: Correlation of SATB1 overexpression with the progression of human rectal cancer. Int J Colorectal Dis 2012, 27:143-150.
  • [11]Chen H, Takahara M, Oba J, Xie L, Chiba T, Takeuchi S, Tu Y, Nakahara T, Uchi H, Moroi Y, Furue M: Clinicopathologic and prognostic significance of SATB1 in cutaneous malignant melanoma. J Dermatol Sci 2011, 64:39-44.
  • [12]Nodin B, Hedner C, Uhlen M, Jirstrom K: Expression of the global regulator SATB1 is an independent factor of poor prognosis in high grade epithelial ovarian cancer. J Ovarian Res 2012, 5:24. BioMed Central Full Text
  • [13]Chu SH, Ma YB, Feng DF, Zhang H, Zhu ZA, Li ZQ, Jiang PC: Upregulation of SATB1 is associated with the development and progression of glioma. J Transl Med 2012, 10:149. BioMed Central Full Text
  • [14]Lu X, Cheng C, Zhu S, Yang Y, Zheng L, Wang G, Shu X, Wu K, Liu K, Tong Q: SATB1 is an independent prognostic marker for gastric cancer in a Chinese population. Oncol Rep 2010, 24:981-987.
  • [15]FitzPatrick DR, Carr IM, McLaren L, Leek JP, Wightman P, Williamson K, Gautier P, McGill N, Hayward C, Firth H, Markham AF, Fantes JA, Bonthron DT: Identification of SATB2 as the cleft palate gene on 2q32-q33. Hum Mol Genet 2003, 12:2491-2501.
  • [16]Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Farinas I, Karsenty G, Grosschedl R: SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell 2006, 125:971-986.
  • [17]Magnusson K, de Wit M, Brennan DJ, Johnson LB, McGee SF, Lundberg E, Naicker K, Klinger R, Kampf C, Asplund A, Wester K, Gry M, Bjartell A, Gallagher WM, Rexhepaj E, Kilpinen S, Kallioniemi OP, Belt E, Goos J, Meijer G, Birgisson H, Glimelius B, Borrebaeck CA, Navani S, Uhlén M, O'Connor DP, Jirström K, Pontén F: SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas. Am J Surg Pathol 2011, 35:937-948.
  • [18]Wang S, Zhou J, Wang XY, Hao JM, Chen JZ, Zhang XM, Jin H, Liu L, Zhang YF, Liu J, Ding YQ, Li JM: Down-regulated expression of SATB2 is associated with metastasis and poor prognosis in colorectal cancer. J Pathol 2009, 219:114-122.
  • [19]Yang MH, Yu J, Jiang DM, Li WL, Wang S, Ding YQ: microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis. J Transl Med 2014, 12:109. BioMed Central Full Text
  • [20]Eberhard J, Gaber A, Wangefjord S, Nodin B, Uhlen M, Ericson Lindquist K, Jirstrom K: A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer. Br J Cancer 2012, 106:931-938.
  • [21]Elebro J, Jirstrom K: Use of a standardized diagnostic approach improves the prognostic information of histopathologic factors in pancreatic and periampullary adenocarcinoma. Diagn Pathol 2014, 9:80. BioMed Central Full Text
  • [22]Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H: Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 2013, 310:1473-1481.
  • [23]Nodin B, Johannesson H, Wangefjord S, DP OC, Ericson-Lindquist K, Uhlen M, Jirstrom K, Eberhard J: Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer. Diagn Pathol 2012, 7:115. BioMed Central Full Text
  • [24]Hanker LC, Karn T, Mavrova-Risteska L, Ruckhaberle E, Gaetje R, Holtrich U, Kaufmann M, Rody A, Wiegratz I: SATB1 gene expression and breast cancer prognosis. Breast 2011, 20:309-313.
  • [25]Iorns E, Hnatyszyn HJ, Seo P, Clarke J, Ward T, Lippman M: The role of SATB1 in breast cancer pathogenesis. J Natl Cancer Inst 2010, 102:1284-1296.
  • [26]Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Kochli OR, Mross F, Dieterich H, Moch H, Mihatsch M, Kallioniemi OP, Sauter : Tissue microarrays for rapid linking of molecular changes to clinical endpoints. Am J Pathology 2001, 159:2249-2256.
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