Transdifferentiation of cervical squamous cell carcinoma with ERBB2 amplification to adenocarcinoma: whole genome sequence analysis and successful control by anti-HER2 therapy

Cancer cells sometimes transdifferentiate into different histological type(s) and tumors with multiple histological types can share a common ancestor cell. However, diagnosis of the origin of multiple tumor lesions with different histological features remains a clinical challenge. A 45-year-old woman with a history of cervical squamous cell carcinoma (CeSq) presented with abdominal pain and vomiting. A surgical operation revealed an ileal tumor and a peritoneal nodule with a small amount of ascites. A histological examination of the ileal tumor demonstrated squamous cell carcinoma, which was consistent with metastasis of cervical cancer, while that of the nodule and ascites showed adenocarcinoma. Whole genome sequencing (WGS) of the CeSq, ileal squamous cell carcinoma (SiSq), and peritoneal adenocarcinoma (PeAd) demonstrated that ERBB2 was commonly amplified in all lesions. Additionally, HPV-16 genome sequences were identified at identical genomic loci in these lesions. A trajectory analysis corroborated that SiSq and PeAd had a shared origin and developed simultaneously at each metastatic site. These results indicate that a subpopulation of the CeSq had transdifferentiated into adenocarcinoma in our patient. Anti-HER2 therapy showed marked effects on the recurrent disease. Our case demonstrates the plasticity of tumor cells and reinforces the potential roles of WGS in the implementation of precision oncology.