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. 2018 Nov;16(5):6238-6244.
doi: 10.3892/ol.2018.9417. Epub 2018 Sep 7.

High concordance of TMPRSS-ERG fusion between primary prostate cancer and its lymph node metastases

Franziska Brandi  1 , Katharina Grupp  2 , Claudia Hube-Magg  1 , Martina Kluth  1 , Dagmar Lang  1 , Sarah Minner  1 , Christina Möller-Koop  1 , Markus Graefen  3 , Hans Heinzer  3 , Maria Christina Tsourlakis  1 , Corinna Wittmer  1 , Frank Jacobsen  1 , Hartwig Huland  3 , Stefan Steurer  1 , Patrick Lebok  1 , Andrea Hinsch  1 , Waldemar Wilczak  1 , Thorsten Schlomm  3   4 , Ronald Simon  1
Affiliations

High concordance of TMPRSS-ERG fusion between primary prostate cancer and its lymph node metastases

Franziska Brandi et al. Oncol Lett. 2018 Nov.

Abstract

Approximately 50% of prostate cancer types harbor the transmembrane protease, serine 2: Erythroblast transformation-specific-related gene (ERG) fusion, resulting in oncogenic expression of the ERG transcription factor. ERG represents an attractive target for potential future anticancer therapy in advanced and metastatic prostate cancer. To better understand whether the analysis of the primary cancer is sufficient to estimate the ERG expression status of the lymph node metastases, the present study examined patterns of immunohistochemical ERG expression in a tissue microarray created from multiple primary and metastatic sites of 77 prostate cancer tissues. Among the identified tumor types, 80% were either entirely ERG-positive (38%) or ERG-negative (42%) across all (at least 9) analyzed different tumor sites. The results were heterogeneous in 20% of the tumor types and typically resulted from small ERG-negative areas within otherwise ERG-positive tumor types. Comparison of the ERG expression status in 51 primary cancer types with at least three interpretable lymph node metastases revealed an entirely identical ERG status in all tumor sites in 75% of the cases, including 16 ERG-positive and 22 ERG-negative cancer types. The remaining 13 cancer types exhibited ERG heterogeneity within the primary tumor, while all metastases had an identical (12 positive and 1 negative) ERG status. The results of the present study revealed a high degree of concordance of the ERG expression status between primary prostate cancer types and their lymph node metastases. Therefore, potential anti-ERG therapy may also be effective against lymph node metastases in the majority of cases of ERG-positive metastatic prostate cancer.

Keywords: immunohistochemistry; nodal metastasis; prostate cancer; serine 2: erythroblast transformation-specific-related gene fusion; tissue microarray; transmembrane protease.

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Figures

Figure 1.
Figure 1.
Representative images of ERG staining intensities in homogeneous cases: (A) Negative, (B) weak, (C) moderate and (D) strong. Original spot size (0.6 mm) ×100 magnification. ERG, protein encoded by the erythroblast transformation-specific-related gene.
Figure 2.
Figure 2.
Fourteen primary prostate cancer cases and their Gleason grade with heterogeneous ERG findings. Red color indicates ERG-positive primary cancer spots, and green color ERG-negative primary spots. Grey color indicates non-analyzable spots. ERG, protein encoded by the erythroblast transformation-specific-related gene.
Figure 3.
Figure 3.
Representative pictures of cases from Fig. 2 with heterogeneous tumor samples e.g., case no. 10 the single positive spot 13 and case no. 32 the single negative spot 11. Note the ERG-positive tumor cells to the right from the dotted line in this spot. Original spot size (0.6 mm) ×100 magnification.
Figure 4.
Figure 4.
Comparison of the ERG status in 49 primary cancers with matched lymph node metastases. ERG, protein encoded by the erythroblast transformation-specific related gene.
See this image and copyright information in PMC

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