title: A new prognostic histopathologic classification of nasopharyngeal carcinoma.
abstract: BACKGROUND
  The current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response.
  
  
  METHODS
  We initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS).
  
  
  RESULTS
  The 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P < 0.001). In multivariate models, patients with MSEC had a shorter OS than patients with EC (HR = 1.44, 95% CI = 1.27-1.62), SC (HR = 2.00, 95% CI = 1.76-2.28), or SCC (HR = 4.23, 95% CI = 3.34-5.38). Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC (HR = 0.67, 95% CI = 0.56-0.80), MSEC (HR = 0.58, 95% CI = 0.49-0.75), and possibly for those with SCC (HR = 0.63; 95% CI = 0.40-0.98), but not for patients with SC (HR = 0.97, 95% CI = 0.74-1.28).
  
  
  CONCLUSIONS
  The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associated with a poor prognosis.
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Hai-Yun
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taibei, 10002, Taiwan, P. R. China.
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Department of Anatomical and Cellular Pathology, Hong Kong Cancer Institute and Sir YK Pao Centre for Cancer, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 10871, P. R. China.
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: To
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, 169608, Singapore.
authors.forename: Jacqueline S G
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Yan-Fen
authors.initials: YF
authors.lastname: Feng
authors.affiliation: Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Health Sciences Practice, Exponent, Inc., Menlo Park, CA, 94025, USA.
authors.forename: Ellen T
authors.initials: ET
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taibei, 10002, Taiwan, P. R. China.
authors.forename: Chen-Ping
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Department of Clinical Oncology, Hong Kong Cancer Institute and Sir YK Pao Centre for Cancer, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 10871, P. R. China.
authors.forename: Michael Koon Ming
authors.initials: MK
authors.lastname: Kam
authors.affiliation: Division of Radiation Oncology, National Cancer Center, Singapore, 169610, Singapore.
authors.forename: Shie-Lee
authors.initials: SL
authors.lastname: Cheah
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, 169608, Singapore.
authors.forename: Ming
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Hui-Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Jie-Hua
authors.initials: JH
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, The Affiliated Hospital of Bengbu Medical College, Bengbu, 233030, Anhui, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, P. R. China.
authors.forename: Pei-Qing
authors.initials: PQ
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Guangxi Medical University, Nanning, 530021, Guangxi, P. R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Hunan Provincial Cancer Hospital, Changsha, 410013, Hunan, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, 350014, Fujian, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Ma-Yan
authors.initials: MY
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Sha
authors.initials: S
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China.
authors.forename: An-Jia
authors.initials: AJ
authors.lastname: Han
authors.affiliation: Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong, P. R. China.
authors.forename: Hai-Gang
authors.initials: HG
authors.lastname: Li
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, P. R. China.
authors.forename: Chun-Kui
authors.initials: CK
authors.lastname: Shao
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: Department of Pathology, Hunan Provincial Cancer Hospital, Changsha, 410013, Hunan, P. R. China.
authors.forename: Tai-Xiang
authors.initials: TX
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Experiment Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Jin-Tian
authors.initials: JT
authors.lastname: Li
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.affiliation: Departments of Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Ernberg
authors.affiliation: Department of Anatomical and Cellular Pathology, Hong Kong Cancer Institute and Sir YK Pao Centre for Cancer, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 10871, P. R. China.
authors.forename: Ho Keung
authors.initials: HK
authors.lastname: Ng
authors.affiliation: Department of Clinical Oncology, Hong Kong Cancer Institute and Sir YK Pao Centre for Cancer, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 10871, P. R. China.
authors.forename: Joseph T S
authors.initials: JT
authors.lastname: Wee
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.|Department of Experiment Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 171 77, Sweden.|Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA.
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.affiliation: Department of Clinical Oncology, Hong Kong Cancer Institute and Sir YK Pao Centre for Cancer, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, 10871, P. R. China. anthorny@cuhk.edu.hk.
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, #651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China. shaojy@sysucc.org.cn.|Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. shaojy@sysucc.org.cn.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D059248:Chemoradiotherapy; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology* / Q000628:therapy*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
keywords: Nasopharyngeal carcinoma; Pathologic classification; Prognosis