Research and Reports in Urology (Apr 2021)
Rapidly Progressing Urothelial Carcinoma Due to a Rare TP53 (p.Arg110Pro) Mutation: A Case Report and Review of the Literature
Abstract
Ragheed Saoud,1 Thomas H Sanford,2 Stephen M Hewitt,3 Andrea B Apolo,3 Piyush K Agarwal1 1Section of Urology, Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA; 2Department of Urology, Upstate University Hospital, Syracuse, NY, USA; 3Center for Cancer Research, National Cancer Institute, Bethesda, MD, USACorrespondence: Ragheed SaoudSection of Urology, Department of Surgery, The University of Chicago Medicine, 5841 S. Maryland Ave., Rm. J-663, Chicago, IL, 60637, USATel +1 773 702 9757Fax +1 773 926 0732Email [email protected]: We present a case of a 69-year-old male patient diagnosed with high grade (T1 HG) urothelial carcinoma of the bladder who progressed rapidly towards muscle invasive disease and eventually death despite neoadjuvant chemotherapy and radical cystectomy. We postulate that this may be due to a deleterious underlying somatic gene mutation. Molecular pathologic data obtained on the initial, non-muscle invasive tumor and the final cystectomy specimen, revealed the same TP53 mutation (p.Arg110Pro) in both specimens with a variant allele frequency of 44%. The tumor was tested for 50 common gene mutations in urothelial carcinoma and no other identifiable DNA repair mutations were found, suggesting that this specific TP53 aberration, one that has never been reported in the bladder cancer literature, could be particularly deleterious. Knowing that bladder cancer cell lines that lack TP53 are more resistant to cisplatin and because the tumor lacked any other DNA mutation, this patient may have been a candidate for upfront surgery without neoadjuvant chemotherapy. In addition to histological analysis of the tumor, early molecular and cytogenetic characterization of resected tissue is essential in predicting progression and eventual prognosis of the disease based on identifiable gene mutations. Further comparative prospective studies are required to clarify the importance of molecular heterogeneity and subtyping in bladder cancer.Keywords: invasive, missense mutation, mismatch repair gene
