Elevated polymerase I and transcript release factor (PTRF) may portend aggressive disease and poor survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), according to new study findings published in Urologic Oncology.

PTRF, a soluble protein with possible nuclear localization sequences, regulates RNA polymerase I and helps dissociate transcription complexes. It has been implicated in the biology of several malignancies, such as pancreatic and breast cancers.

In a study of 575 UTUCs from 118 Taiwanese and 457 Caucasian patients, high PTRF expression (an H-score of 115 or more) was significantly associated with adverse clinicopathologic features, including multifocal disease, high pathologic tumor stage, nonurothelial differentiation, lymphovascular invasion, and lymph node metastasis. PTRF mRNA expression was also significantly increased in advanced stage UTUC.

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Both Taiwanese and Caucasian patients with high PTRF-expressing UTUCs suffered worse outcomes. High PTRF expression independently predicted a 1.70-, 2.09-, and 2.04-fold increased risk of progression and cancer-specific and overall mortality, respectively, on multivariate analysis, Wen-Jeng Wu, MD, PhD, of Kaohsiung Medical University Hospital in Kaohsiung, Taiwan, and colleagues reported.

High PTRF expression in UTUC biopsy specimens may identify patients with positive lymph nodes or micrometastases. It may also improve perioperative and postoperative management, according to the investigators.

“With further validation, high-risk UTUC patients identified by PTRF IHC [immunohistochemical staining] should be considered for neoadjuvant or adjuvant systemic therapy and frequent disease surveillance,” Dr Wu’s team wrote. The value of extended lymphadenectomy is still uncertain.

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Yeh HC, Margulis V, Singla N, et al. PTRF independently predicts progression and survival in multiracial upper tract urothelial carcinoma following radical nephroureterectomy [published online December 17, 2019]. Urol Oncol. doi:10.1016/j.urolonc.2019.11.010