title: Expression of ERCC1 and TUBB3 in locally advanced cervical squamous cell cancer and its correlation with different therapeutic regimens.
abstract: BACKGROUND
  Several studies in solid tumors have shown that expression of excision repair cross-complementation group 1 (ERCC1) and class III β-tubulin (TUBB3) can predict response to chemoradiotherapy and might be prognostic factors. We assessed the role of ERCC1 and TUBB3 expressions as predictive and prognostic factors in locally advanced cervical squamous cell carcinoma (LACSCC) patients treated with different neoadjuvant regimens.
  
  
  METHODS
  ERCC1 and TUBB3 were detected in 88 patients with LACSCC by immunohistochemical analysis. Sixty-two patients were included in 3 different prospective trials and grouped as follows: vinorelbine or docetaxel (group A, n = 44) and ifosfamide-vinorelbine-cisplatin (group B, n = 18). Both groups were compared with standard cisplatin chemoradiotherapy (group C, n = 26). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were also collected. Univariate and multivariate Cox models were used to analyze the risk factors.
  
  
  RESULTS
  Thirty-five patients (39.8%) and 18 (20.5%) had high ERCC1 and TUBB3 expression, respectively. Both proteins were overexpressed in tumors with unfavorable characteristics. High ERCC1 was associated with advanced FIGO stage (p = 0.034) and progressive disease (49% vs. 28%). Poor DFS (p = 0.021) and OS (p = 0.005) were observed in group C patients with high ERCC1 expression. Multivariate analysis showed that ERCC1 expression, FIGO stage and pretreatment hemoglobin level were significant prognostic factors (p = 0.002, p = 0.008 and p = 0.005, respectively).
  
  
  CONCLUSIONS
  ERCC1 expression could be a predictive and prognostic factor in LACSCC patients who receive cisplatin monotherapy. Conversely, TUBB3 had no impact on survival in patients treated with antimicrotubule agents.
authors.affiliation: Department of Oncology, Hospital Provincial Neuquén, Neuquén - República Argentina.
authors.forename: Ariel O
authors.initials: AO
authors.lastname: Zwenger
authors.forename: Gabriel
authors.initials: G
authors.lastname: Grosman
authors.forename: Julian
authors.initials: J
authors.lastname: Iturbe
authors.forename: Julieta
authors.initials: J
authors.lastname: Leone
authors.forename: Carlos T
authors.initials: CT
authors.lastname: Vallejo
authors.forename: José P
authors.initials: JP
authors.lastname: Leone
authors.forename: Palmira Pérez
authors.initials: PP
authors.lastname: Verdera
authors.forename: Juan E
authors.initials: JE
authors.lastname: Pérez
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Leone
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001918:Brachytherapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000096:biosynthesis; D018450:Disease Progression; D018572:Disease-Free Survival; D004720:Endonucleases / Q000032:analysis* / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007044:Hysterectomy; D007069:Ifosfamide / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis; D010166:Palliative Care; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D014404:Tubulin / Q000032:analysis* / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C498585:TUBB3 protein, human; D014404:Tubulin; D014747:Vinblastine; C071447:ERCC1 protein, human; D004720:Endonucleases; D015080:Mesna; D002945:Cisplatin; D000077235:Vinorelbine; D007069:Ifosfamide