title: Methyl-methanesulfonate sensitivity 19 expression is associated with metastasis and chemoradiotherapy response in esophageal cancer.
abstract: OBJECTIVE
  To investigate the clinical significance of methyl-methanesulfonate sensitivity 19 (MMS19) expression in esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls. MMS19 protein expression was measured by immunohistochemistry. Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin. Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed.
  
  
  RESULTS
  The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens. High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclear expression of MMS19 was found in 35.0%. High cytoplasmic MMS19 expression was associated with regional lymph node metastases (OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases (OR = 13.1, 95%CI: 1.7-103.0; P = 0.002). Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy (OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively. Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC.
  
  
  CONCLUSIONS
  The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC.
authors.affiliation: Jin-Liang Zhang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Jin-Liang Zhang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Jin-Liang Zhang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Jin-Liang Zhang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Jin-Liang Zhang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Luo
authors.affiliation: Jin-Liang Zhang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Jin-Liang Zhang, Qing Yang, Shi-Yong Lin, Guang-Yu Luo, Rong Zhang, Guo-Liang Xu, Department of Endoscopy and Laser, State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000556:secondary / Q000628:therapy*; D016022:Case-Control Studies; D059186:Chemoradiotherapy, Adjuvant; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011829:Radiation Dosage; D012307:Risk Factors; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis*; D016896:Treatment Outcome; D014747:Vinblastine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D014408:Biomarkers, Tumor; C416322:MMS19 protein, human; D014157:Transcription Factors; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Chemoradiotherapy; Esophageal squamous cell carcinoma; Metastases; Methyl-methanesulfonate sensitivity 19; Surgery