Strong cytoplasmic ETV1 expression has a negative impact on prostate cancer outcome

• Published in: Virchows Archiv : an international journal of pathology Vol. 475; no. 4; pp. 457 - 466
• Main Authors: Segalés, Laura, Juanpere, Nuria, Lorenzo, Marta, Albero-González, Raquel, Fumadó, Lluís, Cecchini, Lluís, Bellmunt, Joaquim, Lloreta-Trull, Josep, Hernández-Llodrà, Silvia
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-10-2019; Springer Nature B.V
• Subjects: Aged; Biomarkers, Tumor - analysis; Cytoplasm - metabolism; DNA-Binding Proteins - analysis; DNA-Binding Proteins - biosynthesis; ETS protein; Gene expression; Humans; Immunohistochemistry; Male; Medicine; Medicine & Public Health; Middle Aged; Multivariate analysis; Original Article; Pathology; Prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Protein expression; Proteins; PTEN protein; Transcription Factors - analysis; Transcription Factors - biosynthesis; Tumors; PTEN; ETV1; Overexpression; Prostate cancer; Outcome
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-019-02573-1

Overexpression of
ETS
genes is involved in prostate cancer (PrCa), but there is little information on the non-
ERG
components of this family. We have investigated
ETV1
,
ETV4
, and
ETV5
overexpression, with or without
PTEN
loss, and their association with grade group (GG), pathological stage, focality, and PSA recurrence in PrCa.
ETS
gene expression was analyzed by qPCR in 104 cases. ETV1 and PTEN immunohistochemistry was assessed in TMA sections from 194 additional cases (PSMAR-Biobank, Barcelona, Spain).
ETS
mRNA overexpression was found in 23.1%, being
ETV1
the most frequently overexpressed (18.3%). ETV1 protein overexpression was detected in 30.4% cases (moderate in 19.6%, strong in 10.8%). PTEN protein expression loss was detected in 36.1% cases and was not associated with ETV1. Strong-moderate ETV1 protein overexpression reaches its highest values in GG3–4, whereas its negativity was significantly more common in GG1 tumors (
p
 = 0.034). ETV1-overexpressing tumors were more often unifocal (
p
 = 0.0007) and high stage (
p
 = 0.032). PTEN loss was less common in GG1 (
p
 = 0.012) and showed a trend to be less frequent in pT2 (
p
 = 0.062) tumors. Strong ETV1 immunostaining (histoscore > 177) was associated with shorter time to PSA recurrence in the univariate (
p
 = 0.002) and in the multivariate analysis (
p
 = 0.018). Moreover, when strong ETV1 overexpression was not combined with PTEN loss, its association with PSA recurrence was even stronger (
p
 = 0.0004). In conclusion, non-ERG ETS overexpression, particularly ETV1 overexpression, has a non-negligible role in PrCa. Strong ETV1 protein expression has a negative impact on prostate cancer outcome that seems to be independent of PTEN status.