Supl. 1.

authors

Piotr Chłosta, Paweł Orłowski, Janusz Kopczyński, Artur A. Antoniewicz, Jakub Dobruch, Paweł Klonowski, Jacek Sygut, Andrzej Borówka: Oddział Urologii, Świętokrzyskie Centrum Onkologii w Kielcach
Zakład Patologii Nowotworów, Świętokrzyskie Centrum Onkologii w Kielcach
Klinika Urologii CMKP I Zespół Dydaktyki Urologicznej – Oddział Urologii Międzyleskiego Szpitala Specjalistycznego w Warszawie

summary

Introduction.

It is hypothesized that the function of neuroendocrine (NE) cells in the prostate may be involved in regulating the growth and differentiation of the developing prostate, and in regulating secretory processes in the mature gland. NE can stimulate the growth of cellular hormonal refractory lines during hormonal treatment. NE cells occur also in about 80% men without irregularity in prostate gland. Proteins Ki -67 are located in all proliferated cells (in phase G1, S, G2, M); the higher proliferation index (the percentage of cells showing the positive expression Ki -67), indicates the higher malignancy of prostate cancer (G) and development of hormone resistance.

Objectives.

Aim of the presented study is evaluation of frequency of neuroendocrine differentiation in prostate cancer (PCA) and its association between proliferation index and percentage of tumor in biopsy cores.

Materials and methods.

Core needle biopsies from 92 PCA patients (mean age 72 yrs; from 47 to 78 yrs), Gleason score ≥7, were immunohistochemically analyzed for NE differentiation, assessment of proliferation index and percentage of tumor biopsy cores taken under transrectal ultrasound control were also analyzed. Mean PSA value was 9.3 ng/mL (4.4-58.3 ng / mL), mean prostate volume 34.2 mL (16-79 mL), the average number of cores 5 (1-9), the average length of the cores 10.09 mm (4.82-20.48 mm), the average number PCA involved cores 3.66 (1-6), whole percentage cores with malignancy 63% (14-100%,) and the mean Gleason score 7.9 (7-10). Tissues laboratory examination was performed after formaldehyde solution keeping, no longer than 24 hrs. PCA was diagnosed during standard histopathologic examination. The percentage of malignancy in biopsy cores was assessed by mathematical analysis of microscopic picture. NE cells were identified using NE antigens, neurospecific enolase (NSE) and an antibody against chromogranin A. The Ki -67 protein was detected using the mouse’s monoclonal antibody MIB1 (1:100), after previous warming the tissue

to temperature 90oC under microwave conditions. NE was detected also using monoclonal antibody DAK -A 3, directed against chromogranin A. As the criteria of significant mitotic activity of PCA cells, defined the index Ki -67 (MIB - 1) >7.4%.

Results.

NE activity was detected 14 (13%) cases. In these males, NE cells were found in 100% positive cores. The proliferative activity of NE cells was not found in cores without malignancy. The positive dependence was found between neuroendocrine differentiation and higher proliferation index (IP) of cancer cells (p <0005): IP 7.5 – 30 was 7.1%, IP 31 – 60 was 21.4%, and IP >60 was 71.5%. There was no relation between NE activity and number/ whole percentage of positive cores, prostate volume, PSA value and Gleason score.

Conclusions. The results of the study suggest, that relation between universally prognostic PCA factors and presence of NE cells in PCA cores does not exist. We found the correlation only between IP of high malignancy PCA cells and NE expression. Final definition of the role of NE differentiation require more investigations, based on long term observations of PCA patients and their methods of treatment.