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Elevated Expression of Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) Is Associated With a Poor Prognosis in Osteosarcoma

Matsuda, Kotaro, MD, PhD; Miyoshi, Hiroaki, MD, PhD; Hiraoka, Koji, MD, PhD; Hamada, Tetsuya, MD, PhD; Nakashima, Kazutaka, MT; Shiba, Naoto, MD, PhD; Ohshima, Koichi, MD, PhD

Clinical Orthopaedics and Related Research®: September 2018 - Volume 476 - Issue 9 - p 1848–1855
doi: 10.1097/CORR.0000000000000379
CLINICAL RESEARCH
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Background Transforming acidic coiled-coil containing protein 3 (TACC3) is expressed during the mitotic phase of nuclear division and regulates microtubules. Recently, high TACC3 expression in tumor cells of various cancers including soft tissue sarcoma has been reported. However, its role in osteosarcoma remains unknown. Because we have few prognostic markers for survival in osteosarcoma, we wanted to investigate the potential role of TACC3 in human osteosarcoma and determine if it is associated with survival.

Questions/purposes (1) Is there a relationship between TACC3 expression and clinicopathologic characteristics such as sex, age (< 20 or ≥ 20 years), histologic type (osteoblastic or others), tumor location (femur or others), American Joint Committee on Cancer staging system (AJCC stage IIA or IIB), tumor necrosis percentage after chemotherapy (< 90% or ≥ 90%), p53 expression (low or high), and Ki-67 expression (low or high)? (2) Is TACC3 expression associated with event-free and overall survival in patients with osteosarcoma?

Methods Forty-six conventional patients with osteosarcoma were treated at our institution from 1989 to 2013. Patients were excluded because of unresectable primary site (two patients) and no chemotherapy (two patients). Patients with metastasis at the initial visit (five patients), without pretreatment biopsy samples (two patients), or clinical charts (two patients) were also excluded. The left 33 patients who received neoadjuvant and adjuvant chemotherapy, which consisted of cisplatin/doxorubicin/methotrexate or cisplatin/doxorubicin/methotrexate/ifosfamide, and completed surgical resection with histologic wide tumor margins. Primary tumor samples before chemotherapy were used in this study. We investigated TACC3 expression using immunohistochemical staining and statistically analyzed the TACC3 expression, clinicopathologic characteristics, and event-free and overall survival in patients with osteosarcoma.

Results High TACC3 expression was observed in 19 of 33 osteosarcoma specimens (58%), and this was associated with larger tumor size (ie, AJCC stage IIB in this study; p = 0.002), higher p53 expression (p = 0.007), and higher Ki-67 expression (p = 0.002). The estimated metastasis-free survival at 5 years was 21% (95% confidence interval [CI], 7%–41%) in patients with high TACC3 expression and 79% (95% CI, 47%–93%) in patients with low TACC3 expression (p < 0.001), and the estimated overall survival at 5 years was 34% (95% CI, 13%–56%) in patients with high TACC3 expression and 86% (95% CI, 54%–96%) in patients with low TACC3 expression (p < 0.001). Furthermore, high TACC3 expression was an independent poor prognostic factor for metastasis-free survival with a hazard ratio of 3.89 (95% CI, 1.07–19.78; p = 0.039) as well as overall survival with 4.41 (95% CI, 1.01–32.97; p = 0.049).

Conclusions High TACC3 expression was associated with aggressive clinicopathologic features and unfavorable prognosis in these patients with osteosarcoma. Our preliminary results suggest that further analysis about mutation or an inactive form of TACC3 would be useful to understand the mechanism of abnormal TACC3 expression in patients with osteosarcoma. If these findings are substantiated in larger studies, TACC3 might be useful for predicting survival and a potential therapeutic target for osteosarcoma.

Level of Evidence Level III, therapeutic study.

K. Matsuda, H. Miyoshi, K. Nakashima, K. Ohshima, Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan

K. Matsuda, K. Hiraoka, T. Hamada, N. Shiba, Department of Orthopedic Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan

H. Miyoshi, Department of Pathology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan, email: miyoshi_hiroaki@med.kurume-u.ac.jp

Each author certifies that neither he nor any member of his immediate family has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Clinical Orthopaedics and Related Research® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA approval status, of any drug or device before clinical use.

Each author certifies that his institution approved approval for the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

Received December 16, 2017

Accepted May 23, 2018

© 2018 Lippincott Williams & Wilkins LWW
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