Focal p53 protein expression and lymphovascular invasion in primary prostate tumors predict metastatic progression

William Gesztes, Cara Schafer, Denise Young, Jesse Fox, Jiji Jiang, Yongmei Chen, Huai Ching Kuo, Kuwong B. Mwamukonda, Albert Dobi, Allen P. Burke, Judd W. Moul, David G. McLeod, Inger L. Rosner, Gyorgy Petrovics, Shyh Han Tan, Jennifer Cullen, Shiv Srivastava, Isabell A. Sesterhenn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

TP53 is one of the most frequently altered genes in prostate cancer. The precise assessment of its focal alterations in primary tumors by immunohistochemistry (IHC) has significantly enhanced its prognosis. p53 protein expression and lymphovascular invasion (LVI) were evaluated for predicting metastatic progression by IHC staining of representative whole-mounted prostate sections from a cohort of 189 radical prostatectomy patients with up to 20 years of clinical follow-up. Kaplan–Meier survival curves were used to examine time to distant metastasis (DM) as a function of p53 expression and LVI status. TP53 targeted sequencing was performed in ten tumors with the highest expression of p53 staining. Nearly half (49.8%) of prostate tumors examined showed focal p53 expression while 26.6% showed evidence of LVI. p53(+) tumors had higher pathologic T stage, Grade Group, Nuclear Grade, and more frequent LVI. p53 expression of > 5% and LVI, individually and jointly, are associated with poorer DM-free survival. TP53 mutations were detected in seven of ten tumors sequenced. Four tumors with the highest p53 expression harbored likely pathogenic or pathogenic mutations. High levels of p53 expression suggest the likelihood of pathogenic TP53 alterations and, together with LVI status, could enhance early prognostication of prostate cancer progression.

Original languageEnglish
Article number5404
JournalScientific Reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022
Externally publishedYes

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