Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients

Maria-Christina Tsourlakis; Annegret Stender; Alexander Quaas; Martina Kluth; Corinna Wittmer; Alexander Haese; Markus Graefen; Stefan Steurer; Ronald Simon; Jan Korbel; Joachim Weischenfeldt; Hartwig Huland; Guido Sauter; Thorsten Schlomm; Sarah Minner

doi:10.1186/s12885-016-2674-6

Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients

Maria-Christina Tsourlakis, Annegret Stender, Alexander Quaas, Martina Kluth, Corinna Wittmer, Alexander Haese, Markus Graefen, Stefan Steurer, Ronald Simon, Jan Korbel, Joachim Weischenfeldt, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Sarah Minner

14 Citationer (Scopus)

Abstract

Background: TMPRSS2:ERG fusions are frequent in prostate cancer, and occur predominantly in young patients. Several studies had proposed intratumoral heterogeneity of these fusions. This study was designed to determine frequency and extent of ERG fusion heterogeneity in early-onset prostate cancer (EO-PCA, <50 years) and in elderly patients. Methods: The prostates from 63 EO-PCA and 62 elderly prostate cancer patients were thoroughly reviewed for presence of cancer foci. All 1592 tumor-containing sections were analyzed by immunohistochemistry for ERG expression. Results: The prostates included in this study contained one tumor focus in 44, two tumor foci in 21, three tumor foci in 32, four tumor foci in 15, and five or more tumor foci in 13 patients. Among 59 cancer foci with ≤3 mm, 19 (32.2 %) were homogeneously ERG positive, 39 66.1 %) were homogeneously ERG negative, and one case (1.7 %) showed a heterogeneous ERG status. The fraction of homogeneously ERG positive cancer foci remained largely constant (14-37 %) with increasing tumor focus diameter but the fraction of heterogeneous ERG findings continuously increased with tumor size and reached 39 % in cancer foci larger than 22 mm. On a patient level, ERG expression was markedly more frequent in EO-PCA than in elderly patients: 13 % of EO-PCA were homogeneously and 62 % were heterogeneously ERG positive. In elderly patients, 3 % of cancers were homogeneously and 57 % were heterogeneously ERG positive (p = 0.0721). Conclusion: These data show that about 20-30 % of prostate cancer foci have early ERG fusions. ERG fusions further occur in about 50 % of initially ERG negative cancer foci during cancer progression. The vast majority of cancers are heterogeneous for TMPRSS2:ERG fusions on a patient level, challenging the concept of classifying prostate cancer patients into "fusion type" and "non-fusion type" prostate cancer.

Originalsprog	Engelsk
Tidsskrift	B M C Cancer
Vol/bind	16
Sider (fra-til)	641
ISSN	1471-2407
DOI	https://doi.org/10.1186/s12885-016-2674-6
Status	Udgivet - 17 aug. 2016
Udgivet eksternt	Ja

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10.1186/s12885-016-2674-6

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Tsourlakis, M.-C., Stender, A., Quaas, A., Kluth, M., Wittmer, C., Haese, A., Graefen, M., Steurer, S., Simon, R., Korbel, J., Weischenfeldt, J., Huland, H., Sauter, G., Schlomm, T., & Minner, S. (2016). Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients. B M C Cancer, 16, 641. https://doi.org/10.1186/s12885-016-2674-6

Tsourlakis, M-C, Stender, A, Quaas, A, Kluth, M, Wittmer, C, Haese, A, Graefen, M, Steurer, S, Simon, R, Korbel, J, Weischenfeldt, J, Huland, H, Sauter, G, Schlomm, T & Minner, S 2016, 'Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients', B M C Cancer, bind 16, s. 641. https://doi.org/10.1186/s12885-016-2674-6

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title = "Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients",

abstract = "Background: TMPRSS2:ERG fusions are frequent in prostate cancer, and occur predominantly in young patients. Several studies had proposed intratumoral heterogeneity of these fusions. This study was designed to determine frequency and extent of ERG fusion heterogeneity in early-onset prostate cancer (EO-PCA, <50 years) and in elderly patients. Methods: The prostates from 63 EO-PCA and 62 elderly prostate cancer patients were thoroughly reviewed for presence of cancer foci. All 1592 tumor-containing sections were analyzed by immunohistochemistry for ERG expression. Results: The prostates included in this study contained one tumor focus in 44, two tumor foci in 21, three tumor foci in 32, four tumor foci in 15, and five or more tumor foci in 13 patients. Among 59 cancer foci with ≤3 mm, 19 (32.2 %) were homogeneously ERG positive, 39 66.1 %) were homogeneously ERG negative, and one case (1.7 %) showed a heterogeneous ERG status. The fraction of homogeneously ERG positive cancer foci remained largely constant (14-37 %) with increasing tumor focus diameter but the fraction of heterogeneous ERG findings continuously increased with tumor size and reached 39 % in cancer foci larger than 22 mm. On a patient level, ERG expression was markedly more frequent in EO-PCA than in elderly patients: 13 % of EO-PCA were homogeneously and 62 % were heterogeneously ERG positive. In elderly patients, 3 % of cancers were homogeneously and 57 % were heterogeneously ERG positive (p = 0.0721). Conclusion: These data show that about 20-30 % of prostate cancer foci have early ERG fusions. ERG fusions further occur in about 50 % of initially ERG negative cancer foci during cancer progression. The vast majority of cancers are heterogeneous for TMPRSS2:ERG fusions on a patient level, challenging the concept of classifying prostate cancer patients into {"}fusion type{"} and {"}non-fusion type{"} prostate cancer.",

keywords = "Journal Article",

author = "Maria-Christina Tsourlakis and Annegret Stender and Alexander Quaas and Martina Kluth and Corinna Wittmer and Alexander Haese and Markus Graefen and Stefan Steurer and Ronald Simon and Jan Korbel and Joachim Weischenfeldt and Hartwig Huland and Guido Sauter and Thorsten Schlomm and Sarah Minner",

year = "2016",

month = aug,

day = "17",

doi = "10.1186/s12885-016-2674-6",

language = "English",

volume = "16",

pages = "641",

journal = "B M C Cancer",

issn = "1471-2407",

publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - Heterogeneity of ERG expression in prostate cancer

T2 - a large section mapping study of entire prostatectomy specimens from 125 patients

AU - Tsourlakis, Maria-Christina

AU - Stender, Annegret

AU - Quaas, Alexander

AU - Kluth, Martina

AU - Wittmer, Corinna

AU - Haese, Alexander

AU - Graefen, Markus

AU - Steurer, Stefan

AU - Simon, Ronald

AU - Korbel, Jan

AU - Weischenfeldt, Joachim

AU - Huland, Hartwig

AU - Sauter, Guido

AU - Schlomm, Thorsten

AU - Minner, Sarah

PY - 2016/8/17

Y1 - 2016/8/17

N2 - Background: TMPRSS2:ERG fusions are frequent in prostate cancer, and occur predominantly in young patients. Several studies had proposed intratumoral heterogeneity of these fusions. This study was designed to determine frequency and extent of ERG fusion heterogeneity in early-onset prostate cancer (EO-PCA, <50 years) and in elderly patients. Methods: The prostates from 63 EO-PCA and 62 elderly prostate cancer patients were thoroughly reviewed for presence of cancer foci. All 1592 tumor-containing sections were analyzed by immunohistochemistry for ERG expression. Results: The prostates included in this study contained one tumor focus in 44, two tumor foci in 21, three tumor foci in 32, four tumor foci in 15, and five or more tumor foci in 13 patients. Among 59 cancer foci with ≤3 mm, 19 (32.2 %) were homogeneously ERG positive, 39 66.1 %) were homogeneously ERG negative, and one case (1.7 %) showed a heterogeneous ERG status. The fraction of homogeneously ERG positive cancer foci remained largely constant (14-37 %) with increasing tumor focus diameter but the fraction of heterogeneous ERG findings continuously increased with tumor size and reached 39 % in cancer foci larger than 22 mm. On a patient level, ERG expression was markedly more frequent in EO-PCA than in elderly patients: 13 % of EO-PCA were homogeneously and 62 % were heterogeneously ERG positive. In elderly patients, 3 % of cancers were homogeneously and 57 % were heterogeneously ERG positive (p = 0.0721). Conclusion: These data show that about 20-30 % of prostate cancer foci have early ERG fusions. ERG fusions further occur in about 50 % of initially ERG negative cancer foci during cancer progression. The vast majority of cancers are heterogeneous for TMPRSS2:ERG fusions on a patient level, challenging the concept of classifying prostate cancer patients into "fusion type" and "non-fusion type" prostate cancer.

AB - Background: TMPRSS2:ERG fusions are frequent in prostate cancer, and occur predominantly in young patients. Several studies had proposed intratumoral heterogeneity of these fusions. This study was designed to determine frequency and extent of ERG fusion heterogeneity in early-onset prostate cancer (EO-PCA, <50 years) and in elderly patients. Methods: The prostates from 63 EO-PCA and 62 elderly prostate cancer patients were thoroughly reviewed for presence of cancer foci. All 1592 tumor-containing sections were analyzed by immunohistochemistry for ERG expression. Results: The prostates included in this study contained one tumor focus in 44, two tumor foci in 21, three tumor foci in 32, four tumor foci in 15, and five or more tumor foci in 13 patients. Among 59 cancer foci with ≤3 mm, 19 (32.2 %) were homogeneously ERG positive, 39 66.1 %) were homogeneously ERG negative, and one case (1.7 %) showed a heterogeneous ERG status. The fraction of homogeneously ERG positive cancer foci remained largely constant (14-37 %) with increasing tumor focus diameter but the fraction of heterogeneous ERG findings continuously increased with tumor size and reached 39 % in cancer foci larger than 22 mm. On a patient level, ERG expression was markedly more frequent in EO-PCA than in elderly patients: 13 % of EO-PCA were homogeneously and 62 % were heterogeneously ERG positive. In elderly patients, 3 % of cancers were homogeneously and 57 % were heterogeneously ERG positive (p = 0.0721). Conclusion: These data show that about 20-30 % of prostate cancer foci have early ERG fusions. ERG fusions further occur in about 50 % of initially ERG negative cancer foci during cancer progression. The vast majority of cancers are heterogeneous for TMPRSS2:ERG fusions on a patient level, challenging the concept of classifying prostate cancer patients into "fusion type" and "non-fusion type" prostate cancer.

KW - Journal Article

U2 - 10.1186/s12885-016-2674-6

DO - 10.1186/s12885-016-2674-6

M3 - Journal article

C2 - 27530104

SN - 1471-2407

VL - 16

SP - 641

JO - B M C Cancer

JF - B M C Cancer

ER -

Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients

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