Histomorphological Changes in the Peritumoral Zone in Patients with Localized Prostate Cancer as Predictors of Disease Progression
The aim of the study was to study dysplastic, hyperplastic and inflammatory changes in the peritumoral zone and their influence on proliferative activity of tumor cells in patients with localized prostate cancer (PC) after radical prostatectomy.
Materials and Methods. Histomorphological examination of surgical tissue samples from the perifocal zone was carried out using light microscopy in 309 patients with localized PC (T1c–T2cN0M0) after radical surgery. High degree of histopathological differentiation was found in 22 patients (7.1%), moderate degree in 283 (91.6%) and low degree in 4 patients (1.3%). Serum prostate-specific antigen concentration was determined by enzyme immunoassay. Proliferative activity of tumor cells was studied using immunohistochemical examination of Ki-67 marker expression in the tumor.
Results. Histomorphological examination of the peritumoral zone made it possible to reveal histopathological processes combined with prostate adenocarcinoma in 257 of 309 (83.2%) patients with localized prostate cancer: nonspecific chronic bacterial prostatitis in 60.2% of cases, high-grade prostatic intraepithelial neoplasia (PIN-2) in 31.1%, benign hyperplastic processes including sclerosing adenosis and their combinations in 21%.
The most pronounced chronic inflammatory changes in the perifocal zone were observed when prostate adenocarcinoma was combined with PIN-2. The presence of concomitant pathology in the perifocal zone led to no statistically significant change in serum prostate-specific antigen level. Proliferative activity of tumor cells increased in patients with PC when concomitant dysplastic processes in the peritumoral zone were combined with proliferation of stromal components in the prostate gland due to chronic prostatitis and sclerosing adenosis.
Conclusion. Perifocally located PIN-1, PIN-2, chronic prostatitis and sclerosing adenosis increase tumor cell proliferation in prostate adenocarcinoma, thus proving their predictor role.
- Sostoyanie onkologicheskoy pomoshchi naseleniyu rossii v 2016 godu [The state of oncological care for the population of Russia in 2016]. Pod red. Kaprina A.D., Starinskogo V.V., Petrovoy G.V. [Kaprin A.D., Starinskiy V.V., Petrova G.V. (editors)]. Moscow: MNIOI im. P.A. Gertsena; 2017; 236 p.
- Sostoyanie onkologicheskoy pomoshchi naseleniyu rossii v 2015 godu [The state of oncological care for the population of Russia in 2015]. Pod red. Kaprina A.D., Starinskogo V.V., Petrovoy G.V. [Kaprin A.D., Starinskiy V.V., Petrova G.V. (editors)]. Moscow: MNIOI im. P.A. Gertsena; 2017; 236 p.
- Lozhkin E.A., Suhanov S.A., Kiryanov N.A. New criteria of morphological assessment of the prognosis of the prostate cancer. Uralskiy meditsinskiy zhurnal 2017; 4(148): 70–72.
- McNeal J.E. Origin and development of carcinoma in the prostate. Cancer 1969; 23(1): 24–34, https://doi.org/10.1002/1097-0142(196901)23:124::aid-cncr28202301033.0.co;2-1.
- Bostwick D.G. Progression of prostatic intraepitelial neoplasia to early invasive adenocarcinoma. Eur Urol 1996; 30(2): 145–152, https://doi.org/10.1159/000474164.
- Allina D.O., Andreeva Iu.Iu., Zavalishina L.E., Kekeeva T.V., Frank G.A. High-grade prostatic intraepithelial neoplasia: state-of-the-art. Arhiv patologii 2015; 77(1): 69–74.
- Gorbunova E.N., Davydova D.A., Krupin V.N. Chronic inflammation and fibrosis as risk factors of the prostatic intraepithelial neoplasia (PIN) and prostate cancer. Sovremennye tehnologii v medicine 2011; 1: 79–83.
- Iijima J., Konno R., Itano N. Inflammatory alterations of the extracellular matrix in the tumor microenvironment. Cancers 2011; 3(3): 3189–3205, https://doi.org/10.3390/cancers3033189.
- Allen M., Jones L.J. Jekyll
and Hyde: the role of the microenvironment on the progression of cancer. J Pathol 2011: 223(2): 162–176, https://doi.org/10.1002/path.2803. - Dennis L.K., Lynch C.F., Torner J.C. Epidemiologic association between prostatitis and prostate cancer. Urology 2002; 60(1): 78–83, https://doi.org/10.1016/s0090-4295(02)01637-0.
- Corn P.G. The tumor microenvironment in prostate cancer: elucidating molecular pathways for therapy development. Cancer Manag Res 2012; 4: 183–193, https://doi.org/10.2147/cmar.s32839.
- Nickel J.C., True L.D., Krieger J.N., Berger R.E., Boag A.H., Young I.D. Consensus development of a histopathological classification system for chronic prostatic inflammation. BJU Int 2001; 87(9): 797–805, https://doi.org/10.1046/j.1464-410x.2001.02193.x.
- Kovylina M.V., Prilepskaya E.A., Sergeiko I.P., Moiseenko T.N., Kolantarev K.B., Govorov A.V., Pushkar D.Yu. Prognostic value of the immunohistochemical markers Ki-67 and p53 after radical prostatectomy. Onkourologija 2014; 1: 49–52.
- Platz E.A., Kulac I., Barber J.R., Drake C.G.,
Joshu C.E., Nelson W.G., Lucia M.S., Klein E.A., Lippman S.M., Parnes H.L., Thompson I.M., Goodman P.J., Tangen C.M., De Marzo A.M. A prospective study of chronic inflammation in benign prostate tissue and risk of prostate cancer: linked PCPT and SELECT cohorts. Cancer Epidemiol Biomarkers Prev 2017; 26(10): 1549–1557, https://doi.org/10.1158/1055-9965.epi-17-0503. - Davidsson S., Fiorentino M., Andrén O., Fang F., Mucci A., Varenhorst E., Fall K., Rider J.R. Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to
risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev 2011; 20(10): 2280–2287, https://doi.org/10.1158/1055-9965.epi-11-0373. - Leone A., Gershman B., Rotker K., Butler C., Fantasia J., Miller A., Afiadata A., Amin A., Zhou A., Jiang Z., Sebo T., Mega A., Schiff S., Pareek G., Golijanin D., Yates J., Karnes R.J., Renzulli J. Atypical small acinar proliferation (ASAP): is a repeat biopsy necessary ASAP? A multi-institutional review. Prostate Cancer Prostatic Dis 2016; 19(1): 68–71, https://doi.org/10.1038/pcan.2015.52.
- Davidsson S., Carlsson J. Prostate cancer and inflammation: the role of miRNAs. EMJ Oncol 2013; 1: 56–60.
- Kuroda N.,
Katto K., Ohtsuki Y.,Hes O., Michal M., Inoue K., Ohara M., Mizuno K., Lee G.H. Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate. Med Mol Morphol 2010; 43(4): 226–230, https://doi.org/10.1007/s00795-009-0449-8.
