br Din OS Dodwell D Wakefield
 Din OS, Dodwell D, Wakefield RJ, Coleman RE. Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out more? Breast Canc Res Treat 2010;120(3):525e38.  Franks AL, Slansky JE. Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer. Anticancer Res 2012;32(4):1119e36.
 Bernatsky S, Ramsey-Goldman R, Foulkes WD, Gordon C, Clarke AE. Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis. Br J Canc 2011;104(9):1478e81.
 Simon TA, Thompson A, Gandhi KK, Hochberg MC, Suissa S. Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis. Arthritis Res Ther 2015;17:212. CCR4 Expression Is Associated With Poor Prognosis in Patients With Early Stage (pN0) Oral Tongue Cancer
Purpose: Chemokine receptors are involved in tumor metastasis and can predict poor prognosis; however, the Filipin III and clinicopathologic relevance of chemokine receptors in early-stage cancer remain largely unknown. This study measured the association between chemokine (C-C motif) receptor-4 (CCR4) expression and prognosis in patients with histologically node-negative (pN0) oral tongue cancer.
Materials and Methods: A retrospective analysis of CCR4 expression data from a consecutive case series of patients with pN0 oral cancer tongue was conducted. The expression of CCR4 by immunohisto-chemistry was investigated and the association between CCR4 expression and clinicopathologic variables and overall and disease-free survivals was evaluated using Kaplan-Meier analysis and a Cox regression model.
Results: CCR4 expression was examined in 128 human tongue cancerous samples (109 tongue squa-mous cell carcinomas [TSCCs] and 19 other types) and 10 normal tongue samples and was found to be highly expressed in tumor tissues compared with normal tissues. CCR4 expression was observed in 64.2% of patients with TSCC and showed a significant association with tumor stage (P = .037). Patients with CCR4-positive expression exhibited poorer overall and disease-free survivals compared with those with CCR4-negative expression (P < .001 and P = .001), and CCR4-positive expression was an independent factor of unfavorable overall and disease-free survivals (P = .002 and P = .007).
Conclusions: This study identified CCR4 as a potential prognostic biomarker for recurrence and survival of patients with pN0 oral tongue cancer. Thus, CCR4 might be a possible therapeutic target for patients with early-stage cancer.
2018 The Authors. Published by Elsevier Inc. on behalf of the American Association of Oral and Maxillofacial Surgeons. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
*Associate Professor, Department of Stomatology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
yLecturer, Department of Dental, Shandong Medical College, Jinan, Shandong, China.
zAssociate Professor, Department of Clinical Laboratory, Jinxiang County People’s Hospital, Jining, Shandong, China.
xAssociate Professor, Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
kAssociate Professor, Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Professor, Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong Province, China.
This project was supported by the Medical and Health Technol-ogy Development Plan of Shandong Province (2013WSB20018), the Shandong Technological Development Project (2016CY-JS01A02), and the Taishan Scholar Program of Shandong Province.
Conflict of Interest Disclosures: None of the authors have a rele-vant financial relationship(s) with a commercial interest.
Address correspondence and reprint requests to Dr Wang: Department of Clinical Laboratory, The Second Hospital of Shan-dong University, No 247 Beiyuan Street, Jinan 250033, People’s Re-public of China; e-mail: [email protected] Received May 23 2018
2018 The Authors. Published by Elsevier Inc. on behalf of the American Association of Oral and Maxillofacial Surgeons. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
WANG ET AL
Carcinoma of the tongue is one of the most frequent malignancies in the oral cavity.1 The major histologic type is tongue squamous cell carcinoma (TSCC), and in China TSCC constitutes more than 95% of oral SCCs. TSCC is more aggressive than other forms of oral SCC for local invasion and spread. Patients with lymph node metastasis usually have an adverse outcome.2 However, even in histologically node-negative (pN0) oral tongue cancer, some patients still have cancer relapse after curative resection and then a poor prognosis.3 Identifying key molecules associated with disease progression in patients with pN0 oral tongue cancer could help predict tumor behavior and guide treatment, thereby improving clin-ical outcomes.