RELATIONSHIP BETWEEN THE EXPRESSION OF ERG/ PBOV1 PROTEINS AND LYMPH NODE METASTASIS AND MORPHOLOGICAL CHARACTERISTICS OF ACINAR ADENOCARCINOMA OF THE PROSTATE
https://doi.org/10.21294/1814-4861-2017-16-3-27-32
Abstract
When examining prostate cancer, a great attention is currently paid to the study of specific molecular characteristics of the tumor. It has been found that TMPRSS2-ERG is the most common fusion gene in prostate cancer. The fusion between TMPRSS2 and ERG/ ETV1 transcription factor genes participating in the processes of growth, differentiation and transformation of cells has been described in prostate cancer. During carcinogenesis, TMPRSS2 allele loses its promoter, and one of the ERG alleles gains that promoter leading to its overexpression in these tumor cells. Prostate and breast cancer overexpressed 1 (PBOV1) promotes proliferation of tumor cells by inhibiting the cell cycle and increasing the level of cyclin D1. It has been shown that the PBOV1 gene expression is regulated by androgens through FOXA-1 and FOXA-2 transcription factors and participates in the organogenesis in the embryo, as well as it controls the division of stem cells in adults, and plays a role in the development of certain types of malignant tumors. The purpose of the study was to analyze the expression of ERG and PBOV1 genes in acinar prostatic adenocarcinoma and evaluate their relationship with morphological characteristics and lymph node metastases. Material and methods. Surgical specimens from 85 patients with stage T1–3N0–3M0 prostate cancer were morphologically studied using standard techniques. All patients underwent radical prostatectomy. Histological type of the tumor was evaluated according to the 2016 WHO classification of tumors, and the tumor grade was assessed using the Gleason scoring system. Immunohistochemical examination was performed according to the standard technique. The expression of ERG (Clone, EP 111) and PBOV1 (Polyclonal) was assessed using histological scoring system. Proliferative activity was analyzed using Ki67 nuclear staining (Clone, SP6). Data analysis was performed using Statistica 10.0. Results. The high expression level of ERG and PBOV1 proteins was associated with tumor grading (Gleason score > 6) and lymph node metastasis. Inflammatory cell infiltration of the tumor was not associated with the frequency of lymph node dissemination. However, the presence of stromal retraction in acinar tumors was found to be associated with more frequent involvement of regional lymph nodes. The level of PBOV1 expression in tumor cells correlated with proliferative activity and associated with tumor invasion into seminal vesicles. Conclusion. The study showed the relationship between ERG /PBOV1 proteins and morphological characteristics of acinar adenocarcinoma of the prostate as well as the frequency of lymph node metastasis, thus indicating prognostic significance of these markers.
About the Authors
N. V. BezgodovaRussian Federation
MD, postgraduate, Pathologic Anatomy Department
SPIN-code: 6986-7752
5, Kooperativny str., 634009-Tomsk
S. V. Vtorushin
Russian Federation
Senior Researcher of the Department of Pathologic Anatomy and Cytology
5, Kooperativny str., 634009-Tomsk
MD, DSc, Professor of Pathological Anatomy Department
2, Moskovskiy Tract, 634050-Tomsk
SPIN-code: 2442-4720
M. V. Zavyalova
Russian Federation
Senior Researcher of the Department of Pathological Anatomy and Cytology
5, Kooperativny str., 634009-Tomsk
MD, DSc, Professor, Head of Pathological Anatomy Department
2, Moskovskiy Tract, 634050-Tomsk
SPIN-code: 1229-0323
References
1. Cheng L., Koch M.O., Juliar B.E., Daggy J.K., Foster R.S., Bihrle R., Gardner T.A. The Combined percentage of Gleason patterns 4 and 5 is the best predictor of cancer progression after radical prostatectomy. J. Clin. Oncol. 2005; 23 (13): 2911–2917. doi: 10.1200/JCO.2005.03.018.
2. Vtorushin S.V., Bezgodova N.V., Zavyalova М.V. Molecular and biological prognostic factors for prostate cancer. Siberian Journal of Oncology. 2017; 16 (1): 82–90. doi: 10.21294/1814-4861-2017-16-1-82-90. [in Russian]
3. Kumar-Sinha C., Tomlins S.A., Chinnaiyan A.M. Recurrent gene fusions in prostate cancer. Nat. Rev. Cancer. 2008; 8 (7): 497–511. doi: 10.1038/nrc2402.
4. Mwamukonda K., Chen Y., Ravindranath L., Furusato B., Hu Y., Sterbis J., Osborn D., Rosner I., Sesterhenn I.A., McLeod D.G., Srivastava S., Petrovics G. Quantitative expression of TMPRSS2 transcript in prostate tumor cells reflects TMPRSS2-ERG fusion status. Prostate Cancer Prostatic Dis. 2010; 13 (1): 47–45. doi: 10.1038/pcan.2009.28.
5. Tomlins S.A., Rhodes D.R., Perner S., Dhanasekaran S.M., Mehra R., Sun X.W., Varambally S., Cao X., Tchinda J., Kuefer R., Lee C., Montie J.E., Shah R.B., Pienta K.J., Rubin M.A., Chinnaiyan A.M. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005; 310 (5748): 644–648. doi: 10.1126/science.1117679.
6. Demichelis F., Fall K., Perner S., Andrén O., Schmidt F., Setlur S.R., Hoshida Y., Mosquera J.M., Pawitan Y., Lee C., Adami H.O., Mucci L.A., Kantoff P.W., Andersson S.O., Chinnaiyan A.M., Johansson J.E., Rubin M.A. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene. 2007; 26: 4569–4599. doi: 10.1038/ sj.onc.1210237.
7. Hessels D., Schalken J.A. Urinary biomarkers for prostate cancer: a review. Asian Journal of Andrology. 2013; 15: 333–339. doi: 10.1038/ aja.2013.6.
8. Liu L., Yoon J.H., Dammann R., Pfeifer G.P. Frequent hypermethylation of the RASSF1A gene in prostate cancer. Oncogene. 2002; 21: 6835–6840. doi: 10.1038/sj.onc.1205814.
9. Kawamoto K., Okino S.T., Place R.F., Urakami S., Hirata H., Kikuno N., Kawakami T., Tanaka Y., Pookot D., Chen Z., Majid S., Enokida H., Nakagawa M., Dahiya R. Epigenetic modifications of RASSF1A gene through chromatin remodeling in prostate cancer. Clin. Cancer Res. 2007; 13: 2541–2548. doi: 10.1158/1078-0432.CCR-06-2225.
10. An G., Ng A.Y., Meka C.S., Luo G., Bright S.P., Cazares L., Wright G.L. Jr., Veltri R.W. Cloning and characterization of UROC28, a novel gene overexpressed in prostate, breast, and bladder cancers. Cancer Res. 2000; 60 (24): 7014–7020.
11. Pan T., Wu R., Liu B., Wen H., Tu Z., Guo J., Yang J., Shen G. PBOV1 promotes prostate cancer proliferation by promoting G1/S transition. Onco Targets Ther. 2016; 9: 787–795. doi: 10.2147/OTT.S92682.
12. Samusik N., Krukovskaya L., Meln I., Shilov E., Kozlov A. PBOV1 Is a Human De Novo Gene with Tumor-Specific Expression That Is Associated with a Positive Clinical Outcome of Cancer. PLoS One. 2013; 8 (2): e56162. doi: 10.1371/journal.pone.0056162.
13. Stepanov I.V., Altybaev S.R., Rachkovsky K.V., Zavyalova М.V., Vtorushin S.V., Afanasyev S.G. Characteristics of lymph node metastasis depending on the phenomenon of tissue retraction in rectal cancer. Oncology bulletin of the Volga region. 2016; 5: 12–18. [in Russian]
Review
For citations:
Bezgodova N.V., Vtorushin S.V., Zavyalova M.V. RELATIONSHIP BETWEEN THE EXPRESSION OF ERG/ PBOV1 PROTEINS AND LYMPH NODE METASTASIS AND MORPHOLOGICAL CHARACTERISTICS OF ACINAR ADENOCARCINOMA OF THE PROSTATE. Siberian journal of oncology. 2017;16(3):27-32. (In Russ.) https://doi.org/10.21294/1814-4861-2017-16-3-27-32