Reassessment of p53 immunohistochemistry thresholds in invasive high grade bladder cancer shows a better correlation with TP53 and FGFR3 mutations |
| |
| Affiliation: | 1. Circulating Biomarkers Laboratory, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro 20550-170, Brazil;2. Graduate Program in Medical Sciences, Rio de Janeiro State University, Rio de Janeiro 20550-170, Brazil;3. Americas Medical City, Barra da Tijuca, Rio de Janeiro 22775-001, Brazil;4. BIOARRAY Therapeutics Inc., Farmington 06032, USA;5. Micro-Imagem Laboratory, Rio de Janeiro 22060-000, Brazil;6. Laboratory of Functional Genomics and Bioinformatics, PTDIS/FIOCRUZ, Rio de Janeiro 21040-900, Brazil;7. Kennedy Faculty, Belo Horizonte, Minas Gerais 31535-040, Brazil;1. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;2. Department of Pathology, University of Colorado, Aurora, CO 80045, USA;3. Palos Verdes Peninsula High School, Rancho Palos Verdes, CA 90275, USA;4. Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte 91010, USA;5. Department of Diabetes and Cancer Discovery Science, City of Hope National Medical Center, Duarte 91010, USA;1. Department of Pediatrics, University of Washington School of Medicine, Seattle Children''s Hospital, Seattle, WA 98105, USA;2. Department of Pediatric Endocrinology, Beaumont Children''s Hospital, Royal Oak, MI 48073, USA |
| |
| Abstract: | FGFR3 mutations are frequently mutually exclusive of TP53 mutations in invasive high grade urothelial carcinoma (HGUC) and p53 immunohistochemistry is often used as a surrogate for TP53 mutations. A 10 % staining cut off has been used in HGUC for designation as p53 positive or negative however, a novel contemporary method we have previously proposed (0% or >50 % - abnormal vs. 1–49 % - wild type) has shown significant correlation with oncologic outcome as well. We aimed to compare how a ≥10 % vs. 0 % and ≥ 50 % cut off p53 assessment method correlates with TP53 and FGFR3 mutation status. Tissue microarrays created from three retrospective cohorts (two cystectomy cohorts (cohort A, n = 206 and cohort B, n = 91; one T1 transurethral resection cohort (cohort C, n = 47)) were stained with p53 and scored by two blinded reviewers using both p53 scoring schemes. 50 cases from cohort A were assessed for TP53 and FGFR3 mutation status using next generation sequencing and FGFR3 mutation status was separately assessed in cohorts B and C using SNaPshot methodology. 202 (58.7 %) and 142 (41.3 %) cases showed abnormal and wild type p53 staining, respectively. Using the 10 % cut off, 254 cases were positive (73.8 %) and 90 cases were negative (26.2 %). 27 (14.4 %) and 15 (30 %) assessed cases demonstrated FGFR3 and TP53 mutations, respectively; 19/27 FGFR3 mutated showed a wild type pattern of p53 expression while 15/15 TP53 mutated tumours showed an abnormal pattern of p53 expression. There was a significant correlation between the contemporary p53 scoring scheme and TP53 and FGFR3 mutations (p < 0.0001 and p = 0.002, respectively). Improved sensitivity, specificity, positive predictive value, and negative predictive value for TP53 mutation was also seen compared to the 10 % cut off; specifically, the sensitivity and negative predictive value were 100 %. These findings might be of clinical relevance in the era of precision medicine. |
| |
| Keywords: | Bladder cancer Urothelial carcinoma p53 immunohistochemistry |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
