Expression of ERCC1 and TUBB3 in locally advanced cervical squamous cell cancer and its correlation with different therapeutic regimens

Int J Biol Markers. 2015 Jul 22;30(3):e301-14. doi: 10.5301/jbm.5000161.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brachytherapy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy
  • Cisplatin / administration & dosage
  • Cisplatin / therapeutic use
  • Clinical Trials, Phase II as Topic
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / biosynthesis
  • Disease Progression
  • Disease-Free Survival
  • Endonucleases / analysis*
  • Endonucleases / biosynthesis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hysterectomy
  • Ifosfamide / administration & dosage
  • Kaplan-Meier Estimate
  • Mesna / administration & dosage
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / biosynthesis
  • Palliative Care
  • Prognosis
  • Radiotherapy, Adjuvant
  • Tubulin / analysis*
  • Tubulin / biosynthesis
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine

Substances

  • Antineoplastic Agents, Alkylating
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • TUBB3 protein, human
  • Tubulin
  • Vinblastine
  • ERCC1 protein, human
  • Endonucleases
  • Mesna
  • Cisplatin
  • Vinorelbine
  • Ifosfamide