Benign prostat hiperplazisi, yüksek gradeli prostatik intraepitelyal neoplazi ve prostat adenokarsinomunda doku büyüme faktör ve reseptörleri
Tez Türü: Doktora
Tezin Yürütüldüğü Kurum: İstanbul Üniversitesi-Cerrahpaşa, Cerrahpaşa Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Türkiye
Tez Danışmanı: Nur Ahmet Erözenci
Tezin Onay Tarihi: 2002
Tezin Dili: Türkçe
Özet:
OBJECTIVE: Cancer is a complex process that includes genetic changes at various levels in the cell cycle, uncontrolled cell division and growth, invasion and metastasis. It is well known that growth factors play a major role in the cell cycle. This study was designed to determine the role of growth factors (EGFR, TGF-a and insulin like growth factor-1 receptor (IGFR-1)) in prostate cancer.
MATERIALS AND METHODS: The pathology specimens of 30 patients who had undergone retropubic radical prostatectomy (RRP) for T2a-T3b prostate cancer and had moderately differentiated prostatic adenocarcinoma were immunohistochemically stained for EGF, IGF and TGF receptors. A further 7 patients who underwent suprapubic prostatectomy for BPH served as the control group. PIN areas in the radical prostatectomy specimens were studied separately. None of the patients with prostatic adenocarcinomas had received previous endocrine treatment.
In an immunohistochemical study, EGFR (Neomarkers, MS-378, R7), TGF-a (Neomarkers, MS-670, R7) ve IGFR-1 (a submit) Ab-1 (Neomarkers, MS-641, R7) antibodies were applied to each specimen. All samples were evaluated by one observer who was unaware of the clinical information. Staining properties of the study samples were scored on a five-point scale according to intensity and density: 0- no, 1- focal, 2-weak, 3- moderate and 4- strong staining. For statistical purposes, these scores are grouped into 2, group I consisting of those with no, focal or weak staining and group II consisting of those with moderate or strong staining. Statistical analysis was performed by chi-square and Kruskal-Wallis tests.
RESULTS: The median age of the patients was 63.1+5.5 (53-75) years and the median preoperative serum PSA level was 16.8+18.7 (1.4-100.4) ng/ml. Thirty of 37 patients were performed RRP due to organ-limited prostate cancer, and the remaining 7 were treated with suprapubic prostatectomy due to BPH. EGFR showed strong staining in all cases of BPH. There was weak or no staining in 72% of the patients with prostatic adenocarcinoma and all foci of PIN. This strong staining in BPH was statistically significant, compared to the ones seen in PIN and prostatic adenocarcinoma (c2=26, p=0.000). When the average scores of staining with EGFR of these three tissues were compared, it was found that the average EGFR staining in BPH was significantly higher than the others (Kruskal-Wallis, p=0.000). TGF-a expression was more intense in prostatic adenocarcinoma and in PIN compared to BPH (c2=14.27, p=0.001). Also, when the average of TGF-a staining score was compared, scores of prostate adenocarcinoma and PIN were significantly higher than the scores of BPH (Kruskal-Wallis, p=0.02). In all of the three tissues, there was no statistically significant difference in terms of IGFR-1 staining (c2=0.16, p=0.919). There was also no statistical difference regarding the average scores of the three tissues (Kruskal-Wallis, p=0.02).
CONCLUSION: EGFR staining was found to be significantly higher in BPH tissue, but lower in PIN and prostatic carcinoma tissues. TGF-a expression was found to be significantly lower in BPH tissue, but higher in PIN and prostatic carcinoma tissues. IGFR-1 staining demonstrated equivalent positivity in all the three tissues. EGFR and TGF-a‘s showing an immune reactivity similar to the carcinoma tissue but different from the BPH tissue in high-grade PIN suggests that this lesion is phenotypically similar to prostate adenocarcinoma, and TGF-a and EGFR may play important roles in development of malignant and nonmalignant diseases of prostate.