Cellular and Molecular Biology


The combination of strong immunohistochemical mtTFA expression and a high survivin index predicts a shorter disease-specific survival in pancreatic ductal adenocarcinoma

Tomoko Kimura1, Shohei Kitada2,3, Hidetaka Uramoto4, Li Zhi2,5, Yuichiro Kawatsu1, Toru Takeda1, Seichi Horie1, Atsunori Nabeshima2, Hirotsugu Noguchi2, Yasuyuki Sasaguri2,6, Hiroto Izumi7, Kimitoshi Kohno8 and Sohsuke Yamada2

Department of 1Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan, Departments of 2Pathology and Cell Biology, 3Urology, 4Second Department of Surgery, 7Occupational Pneumology, and 8The President Laboratory, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, 5Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, People’s Republic of China and 6Laboratory of Pathology, Fukuoka Wajiro Hospital, Fukuoka, Japan

Offprint requests to: Sohsuke Yamada, MD, PhD, Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. e-mail: sousuke@med.uoeh-u.ac.jp

Summary. Mitochondrial transcription factor A (mtTFA) plays a crucial role in both the transcription and maintenance of mitochondrial DNA. A high expression of mtTFA has been demonstrated in several solid tumors, and is closely associated with cancer cell survival/apoptosis and growth. However, its expression pattern in pancreatic ductal adenocarcinoma (PAC) remains to be elucidated. Additionally, our groups have recently revealed that a subset of apoptosis-related genes is strongly regulated by mtTFA, and that two putative mtTFA binding sites are present in the promoter region of the survivin gene, which is a member of the inhibitor-of-apoptosis protein family. We therefore investigated the correlation of the immunohistochemical mtTFA expression and the survivin index with various clinicopathological variables and the prognosis, using 70 paraffin-embedded tumor samples from patients with surgically-resected PAC. The mtTFA expression or survivin index was considered to be strong or high when >=30% or 10% of the PAC cells showed positive staining, respectively. Strong mtTFA expression and/or a high survivin index was revealed to have a significant relationship to a pathologically high tumor grading and advanced tumor stage. Moreover, mtTFA showed significantly high co-expression with survivin. Univariate and multivariate analyses demonstrated that both the strong mtTFA expression and high survivin index groups had significantly shorter survival rates, especially within the first two years postoperatively. The combination of strong mtTFA expression and a high survivin index may predict a poor prognosis in patients with PAC, and these new biomarkers might offer useful information for the early clinical management. Histol Histopathol 30, 193-204 (2015)

Key words: Pancreatic ductal adenocarcinoma (PDA), mtTFA, Advanced stage, Survivin, Prognosis

DOI: 10.14670/HH-30.193