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

• Published in: Scientific reports Vol. 10; no. 1; p. 18734
• Main Authors: Watanabe, Takafumi, Nanamiya, Hideaki, Kojima, Manabu, Nomura, Shinji, Furukawa, Shigenori, Soeda, Shu, Tanaka, Daisuke, Isogai, Takao, Imai, Jun-ichi, Watanabe, Shinya, Fujimori, Keiya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-10-2020; Nature Publishing Group
• Subjects: 631/208; 631/67; Adenocarcinoma; Biomarkers - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - surgery; Cervical cancer; Class I Phosphatidylinositol 3-Kinases - genetics; Female; Humanities and Social Sciences; Humans; Hysterectomy; Hysterectomy - methods; Lymph nodes; Lymph Nodes - metabolism; Medical prognosis; Metastases; Metastasis; multidisciplinary; Mutation; Mutation - genetics; p53 Protein; Prognosis; Proto-Oncogene Proteins p21(ras) - genetics; Science; Science (multidisciplinary); Squamous cell carcinoma; Tumor Suppressor Protein p53 - genetics; Tumorigenesis; Tumors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - surgery
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-72518-1

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.