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ERBB2 mutation: A promising target in non-squamous cervical cancer
Libing Xiang1, Wei Jiang1, Shuang Ye1
1Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Gynecologic Oncology
|December 28, 2017
Summary
ERBB2 mutations occur in 3.15% of invasive cervical cancers, particularly in non-squamous types. These mutations may impact prognosis and suggest potential for targeted therapies like tyrosine kinase inhibitors.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2) mutations are identified in a portion of invasive cervical cancer (ICC) cases.
- However, the full scope of ERBB2 mutations, their clinical relevance, HPV genotype links, and prognostic impact in ICC remain incompletely understood.
Purpose of the Study:
- To investigate the prevalence, mutation spectrum, clinicopathological correlations, HPV genotype associations, and prognostic significance of ERBB2 mutations in invasive cervical cancer.
- To evaluate the potential for targeted therapies based on ERBB2 mutation status.
Main Methods:
- Analysis of 1015 invasive cervical cancer samples.
- Detection of mutations in ERBB2, KRAS, and PIK3CA genes using cDNA-based Sanger sequencing.
Main Results:
- Somatic ERBB2 mutations were found in 3.15% of ICC patients.
- ERBB2 mutation rates were significantly higher in adenocarcinoma, adenosquamous carcinoma, and neuroendocrine carcinoma compared to squamous cell carcinoma (P=0.004).
- Concurrent PIK3CA or KRAS mutations were observed in 18.75% of ERBB2-mutated cases. ERBB2-mutated ICCs showed varied prognostic outcomes compared to wild-type or other mutated ICCs.
Conclusions:
- The findings support clinical trials of tyrosine kinase inhibitors for ERBB2-mutated cervical cancer.
- Non-squamous cell carcinomas represent a priority group for ERBB2-targeted therapy.
- Concurrent PIK3CA/RAS mutations warrant consideration in clinical trial design for ERBB2-mutated ICC.
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