p53 and MDM2 expression in primary and metastatic testicular germ cell tumors: Association with clinical outcome.

Abstract:

BACKGROUND:Testicular germ cell tumors (TGCTs) are highly sensitive to platinum-based chemotherapy, and wild-type p53 seems to play a pivotal role in this susceptibility. On the other hand, overexpression of MDM2 seems to entail treatment resistance and unfavorable prognosis. OBJECTIVES:We aimed to describe p53 and MDM2 immunoexpression in a well-characterized cohort of primary and metastatic TGCTs and evaluate associations with clinicopathological and prognostic variables, including survival. MATERIALS AND METHODS:237 primary tumor samples and 12 metastases were evaluated for p53 and MDM2 immunoexpression using digital image analysis. Clinical records of all patients were reviewed for baseline clinical/pathologic characteristics and follow-up. RESULTS:A significant positive correlation between p53 and MDM2 H-scores was found (rs  = 0.590, P < .0001). Non-seminomas showed significantly higher expression levels of both p53 and MDM2 (P = .0002, P < .0001), which peaked in embryonal carcinomas and choriocarcinomas. Percentage of immunoexpressing cells and H-score were significantly higher in chemo-treated metastases compared with chemo-naïve primary tumors for MDM2 (P ≤ .0001 for both), but not for p53 (P = .919 and P = .703, respectively). Cases with higher MDM2 immunoexpression showed a statistically significant trend for association with poorer prognosis (P = .043). Relapse/progression-free survival at 12 months post-diagnosis was lower in the "MDM2-high" (≥P50) vs. the "MDM2-low" (

journal_name

Andrology

journal_title

Andrology

authors

Lobo J,Alzamora MA,Guimarães R,Cantante M,Lopes P,Braga I,Maurício J,Jerónimo C,Henrique R

doi

10.1111/andr.12814

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

1233-1242

issue

5

eissn

2047-2919

issn

2047-2927

journal_volume

8

pub_type

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