Expression of p53 is significantly associated with recurrence-free survival and overall survival in pleuropulmonary blastoma (PPB): a report from the International Pleuropulmonary Blastoma/DICER1 Registry.
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
07
10
2020
accepted:
29
12
2020
revised:
29
12
2020
pubmed:
28
2
2021
medline:
27
1
2022
entrez:
27
2
2021
Statut:
ppublish
Résumé
Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic), type II (cystic and solid), and type III (solid). Prognosis varies by PPB type. Most cases are associated with a germline pathogenic mutation in DICER1; however, there is limited data on the factor(s) at a cellular level that drive progression from type I to type III. In this study, we evaluated the expression of p53 and its prognostic implications. A total of 143 PPB cases were included in the study with the following distribution in PPB types: Ir (14%), I (23%), II (32%), and III (31%). P53 expression by immunohistochemistry (IHC) was recorded as four groups: 0%, 1-25%, 26-75%, and 76-100%. All type I PPBs showed 0-25% p53 expression compared to the higher p53 expression (>25%) in type III PPB (p < 0.0001), to support the argument that p53 has a role in tumor progression. In addition, type Ir with the architectural hallmarks of type I PPB, but lacking the primitive cell population, has negligible p53 expression. High p53 expression (staining observed in >25% of the tumor cells) was significantly associated with age over 1 year (p = 0.0033), neoadjuvant therapy (p = 0.0009), positive resection margin (p = 0.0008) and anaplasia (p < 0.0001). P53 expression was significantly associated with recurrence-free survival (p < 0.0001) and overall survival (p = 0.0350), with higher p53 expression associated with worse prognosis. Comparisons of concordance statistics showed no significant difference in prognostication when using morphologic types compared to p53 expression groups (p = 0.647). TP53 sequence was performed in 16 cases; the most common variant identified was a missense variant (12 cases), and in one case a frameshift truncating variant was noted. Based on these findings, we recommend performing p53 IHC in all newly diagnosed cases of types II and III PPB to further aid in risk stratification.
Identifiants
pubmed: 33637876
doi: 10.1038/s41379-021-00735-8
pii: S0893-3952(22)00600-7
pmc: PMC9236228
mid: NIHMS1816892
doi:
Substances chimiques
Biomarkers, Tumor
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1104-1115Subventions
Organisme : NCI NIH HHS
ID : R01 CA143167
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA244940
Pays : United States
Références
Manivel JC, Priest JR, Watterson J, Steiner M, Woods WG, Wick MR, et al. Pleuropulmonay blastoma. the so-called pulmonary blastoma of childhood. Cancer. 1988;62:1516–26.
doi: 10.1002/1097-0142(19881015)62:8<1516::AID-CNCR2820620812>3.0.CO;2-3
Dehner LP. Pleuropulmonary blastoma is the pulmonary blastoma of childhood. Semin Diagn Pathol. 1994;11:144–51.
pubmed: 7809508
Messinger YH, Stewart DR, Priest JR, Williams GM, Harris AK, Schultz KAP, et al. Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the international pleuropulmonary blastoma registry. Cancer. 2015;121:276–85.
doi: 10.1002/cncr.29032
Priest JR, Watterson J, Strong L, Huff V, Woods WG, Byrd RL, et al. Pleuropulmonary blastoma: A marker for familial disease. J Pediatr. 1996;128:220–4.
doi: 10.1016/S0022-3476(96)70393-1
Schultz KAP, Stewart DR, Kamihara J, Bauer AJ, Merideth MA, Stratton P, et al. DICER1 Tumor predisposition. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al. editors. GeneReviews® 2020.
Hill DA, Jarzembowski JA, Priest JR, Williams G, Schoettler P, Dehner LP. Type i pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry. Am J Surg Pathol. 2008;32:282–95.
doi: 10.1097/PAS.0b013e3181484165
Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, et al. DICER1 mutations in familial pleuropulmonary blastoma. Science (80-). 2009;325:965.
doi: 10.1126/science.1174334
Pugh TJ, Yu W, Yang J, Field AL, Ambrogio L, Carter SL, et al. Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences. Oncogene. 2014;33:5295–302.
doi: 10.1038/onc.2014.150
Guedes LB, Almutairi F, Haffner MC, Rajoria G, Liu Z, Klimek S, et al. Analytic, preanalytic, and clinical validation of p53 IHC for detection of TP53 missense mutation in prostate cancer. Clin Cancer Res. 2017;23:4693–703.
doi: 10.1158/1078-0432.CCR-17-0257
Iggo R, Gatter K, Bartek J, Lane D, L HA. Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet. 1990;335:675–9.
doi: 10.1016/0140-6736(90)90801-B
Zuppan CW, Beckwith JB, Luckey DW. Anaplasia in unilateral Wilms’ tumor: a report from the National Wilms’ Tumor Study Pathology Center. Hum Pathol. 1988;19:1199–209.
doi: 10.1016/S0046-8177(88)80152-7
Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res. 2001;11:863–74.
doi: 10.1101/gr.176601
Harrell JrFE, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247:2543–6.
doi: 10.1001/jama.1982.03320430047030
Therneau TM, Watson DA. The concordance statistic and the cox mode. Tech Rep. 2017;85:1–16.
Priest JR, McDermott MB, Bhatia S, Watterson J, Manivel JC, Dehner LP. Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer. 1997;80:147–61.
doi: 10.1002/(SICI)1097-0142(19970701)80:1<147::AID-CNCR20>3.0.CO;2-X
Priest JR, Hill DA, Williams GM, Moertel CL, Messinger Y, Finkelstein MJ, et al. Type I pleuropulmonary blastoma: a report from the international pleuropulmonary blastoma registry. J Clin Oncol. 2006;24:4492–8.
doi: 10.1200/JCO.2005.05.3595
Pacinda SJ, Ledet SC, Gondo MM, Langston C, Brown RW, Carmona PA, et al. p53 and MDM2 immunostaining in pulmonary blastomas and bronchogenic carcinomas. Hum Pathol. 1996;27:542–6.
doi: 10.1016/S0046-8177(96)90159-8
Murnyak B, Hortobagyi T. Immunohistochemical correlates of TP53 somatic mutations in cancer. Oncotarget. 2016;7:64910–20.
doi: 10.18632/oncotarget.11912
Lane DP. p53, guardian of the genome. Nature. 1992;358:15–6.
doi: 10.1038/358015a0
Levine AJ, Perry ME, Chang A, Silver A, Dittmer D, Wu M, et al. The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer. 1994;69:409–16.
doi: 10.1038/bjc.1994.76
Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, et al. p14(ARF) links the tumour suppressors RB and p53 [5]. Nature. 1998;395:124–5.
doi: 10.1038/25867
Kusafuka T, Kuroda S, Inoue M, Ara T, Yoneda A, Oue T, et al. P53 gene mutations in pleuropulmonary blastoma. Pediatr Hematol Oncol. 2002;19:117–28.
doi: 10.1080/08880010252825704
Vargas SO, Korpershoek E, Kozakewich HPW, De Kruger RR, Fletcher JA, Perez-Atayde AR. Cytogenetic and p53 profiles in congenital cystic adenomatoid malformation: insights into its relationship with pleuropulmonary blastoma. Pediatr Dev Pathol. 2006;9:190–5.
doi: 10.2350/06-01-0025.1