Nucleotide excision repair protein ERCC1 and tumour-infiltrating lymphocytes are potential biomarkers of neoadjuvant platinum resistance in high grade serous ovarian cancer

Gynecol Oncol. 2018 Nov;151(2):306-310. doi: 10.1016/j.ygyno.2018.08.030. Epub 2018 Sep 5.

Abstract

Objective: ERCC1 is a nucleotide excision repair protein that may have a role in drug resistance in high grade serous ovarian cancer (HGSOC). We hypothesized that ERCC1 expression and tumour infiltrating lymphocytes (TILS) are induced by chemotherapy in HGSOC, which may be prognostically useful.

Methods: 115 HGSOC patients were used for this study. 92 (80%) of the tissue analysed had not been exposed to platinum chemotherapy. The remaining 20% (n = 23) of cases received combination or monotherapy with carboplatin before tissue was collected. Immunohistochemistry was used to score for ERCC1 expression and morphology to score for TILs. Correlation analysis of all clinical parameters, TILs and ERCC1 and Kaplan-Meier survival analysis was performed using the ERCC1 and TILs scoring parameters (0, 1, 2 or 3).

Results: ERCC1 expression was 2-fold higher in the neoadjuvant chemotherapy group compared to the primary cytoreductive surgery group (p < 0.0001). The mean overall survival for the neoadjuvant group with high ERCC1 was 141.6 ± 20.2 months which was significantly longer than absent ERCC1 survival of 61 + 22.6 months (p = 0.028). ERCC1 score strongly correlated with TILs score across the whole cohort (0.349, p = 1.3 × 10-4) suggesting there is a relationship between ERCC1 expression and TILs, but this requires further investigation.

Conclusion: In conclusion, ERCC1 was identified as a potential biomarker of platinum response overall survival in HGSOC undergoing neoadjuvant HGSOC treatment.

Keywords: ERCC1; Neoadjuvant chemotherapy; Ovarian cancer; Resistance; Tumour-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / immunology
  • Carboplatin / pharmacology*
  • Chemotherapy, Adjuvant
  • Cytoreduction Surgical Procedures / methods
  • DNA-Binding Proteins / biosynthesis*
  • Drug Resistance, Neoplasm / immunology
  • Endonucleases / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Neoadjuvant Therapy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / surgery
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Carboplatin
  • ERCC1 protein, human
  • Endonucleases