Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening

• Published in: International journal of urology 2018-02, Vol.25 (2), p.151-156
• Main Authors: Urakami, Shinji, Inoshita, Naoko, Oka, Suguru, Miyama, Yu, Nomura, Sachio, Arai, Masami, Sakaguchi, Kazushige, Kurosawa, Kazuhiro, Okaneya, Toshikazu
• Format: Article
• Language: English
• Subjects: Cancer; DNA mismatch repair proteins; DNA repair; Genetic recombination; Genetic screening; immunohistochemistry; Lynch syndrome; Malignancy; Mismatch repair; MLH1 protein; MSH2 protein; MSH6 protein; Papilloma; Proteins; Tumor cells; Tumors; universal screening; upper urinary tract cancer; Urinary tract; Urogenital system; Urothelial cancer; Urothelial carcinoma; Yeast
• ISSN: 0919-8172; 1442-2042
• DOI: 10.1111/iju.13481

Objectives To assess the detection rate of putative Lynch syndrome‐associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics. Methods A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. For all suspected mismatch repair‐deficient cases, MMR genetic testing was recommended and clinicopathological features were examined. Results Loss of mismatch repair proteins was found in seven patients (5%) who were thus categorized as putative Lynch syndrome‐associated upper urinary tract urothelial cancer. Five of these patients showed dual loss of MSH2/MSH6. Two patients were confirmed to be MSH2 germline mutation carriers. Histologically, all seven tumors were low‐grade atypical urothelial carcinoma and showed its unique histological features, such as an inverted papilloma‐like growth pattern and a villous to papillary structure with mild stratification of tumor cells. Six tumors had no invasion of the muscularis propria. No recurrence or cancer‐related deaths were reported in these seven patients. Just three patients met the revised Amsterdam criteria. Conclusions This is the first report that universally examined mismatch repair immunohistochemical screening for upper urinary tract urothelial cancers. The prevalence (5%) of putative Lynch syndrome‐associated upper urinary tract urothelial cancers is much higher than we had expected. We ascertained that putative Lynch syndrome‐associated upper urinary tract urothelial cancers were clinically in the early stage and histologically classified into low‐grade malignancy with its characteristic pathological features. The clinicopathological characteristics that we found in the present study could become additional possible markers in the diagnosis of Lynch syndrome‐associated upper urinary tract urothelial cancers.