Clinical implication of oncogenic somatic mutations in early-stage cervical cancer with radical hysterectomy

Sci Rep. 2020 Oct 30;10(1):18734. doi: 10.1038/s41598-020-72518-1.

Abstract

It is well known that tumour initiation and progression are primarily an accumulation of genetic mutations. The mutation status of a tumour may predict prognosis and enable better selection of targeted therapies. In the current study, we analysed a total of 55 surgical tumours from stage IB-IIB cervical cancer (CC) patients who had undergone radical hysterectomy including pelvic lymphadenectomy, using a cancer panel covering 50 highly mutated tumorigenesis-related genes. In 35 patients (63.6%), a total 52 mutations were detected (58.3% in squamous cell carcinoma, 73.7% in adenocarcinoma), mostly in PIK3CA (34.5%) and KRAS and TP53 (9.1%). Being mutation-positive was significantly correlated with pelvic lymph node (PLN) metastasis (P = 0.035) and tended to have a worse overall survival (P = 0.076). In particular, in the patients with squamous cell carcinoma, there was a significant association between being mutation-positive and relapse-free survival (P = 0.041). The patients with PLN metastasis had a significantly worse overall survival than those without (P = 0.006). These results indicate that somatic mutation status is a predictive biomarker for PLN metastasis in early-stage CC, and is consequently related to poor prognosis. Therefore, comprehensive genetic mutations, rather than a single genetic mutation, should be examined widely in order to identify novel genetic indicators with clinical usefulness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Female
  • Humans
  • Hysterectomy / methods*
  • Lymph Nodes / metabolism
  • Mutation / genetics*
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / surgery

Substances

  • Biomarkers
  • KRAS protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins p21(ras)