Prostatın Benign, Premalıgn Ve Malign Lezyonlarında; Proliferatif Aktivite, Anjiyogenezis, Bazal Membran Ve Apoptozis’in İmmunohistokimyasal Ve Histopatolojik Olarak Değerlendirilmesi

Prostat karsinomu (PK) erkeklerde görülen en yaygın karsinomdur. Kanserden ölüm nedenleri içerisinde, akciğer karsinomundan sonra ikinci sırada yer almaktadır. Son yıllarda tanımlanan prostatik intraepitelial neoplazi (PİN), prostat karsinomunun öncül lezyonları arasında yer almaktadır. Prostat karsinomunda tanı zorluğu oluşturan PİN’in, prostat karsinomu ve benign prostat hiperplazilerinden (BPH) ayrımı önemlidir. Bu çalışmada, PIN’in BPH ve prostat karsinomu olgularında, Ki-67, CD31 ve Laminin immünreaktiviteleri ve apoptozis indeksinin ayırıcı tanıdaki yerinin araştırılması amaçlandı. Atatürk Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı laboratuarında 1991 – 2001 yılları arasında tanı konan 50 prostat adenokarsinomu, 50 prostatik intraepitelial neoplazi ve 50 benign prostat hiperplazisi olmak üzere 150 olguya ait örnekler çalışmaya alındı. Olgulardan elde edilen parafin kesitlere immunohistokimyasal yöntemle Ki-67, CD31, Laminin uygulandı. Ayrıca apoptotik indeksi değerlendirmek için aynı olgulara ait parafin bloklardan hemotoksilen-eozin boyalı kesitler hazırlandı. Ki-67 için nükleer koyu kahverengi boyanma, CD31 için stoplazmik endotelial hücrelerin boyanması ve Laminin için ise gland epiteli altındaki bazal membrandaki kesintisiz lineer boyanma pozitif olarak kabul edildi. Ki-67 immunreaktivitesi, prostat karsinomunda en yüksek ve BPH’da en düşüktü. Ayrıca prostat karsinomu olgularında Ki-67 immunreaktivitesi, PIN olgularından anlamlı derecede yüksek iken (p<0.001), PİN ile BPH arasında p<0.05 düzeyindeydi. CD31 immunreaktivitesi ve apoptotik indeks açısından bakıldığında, değerler en yüksek olarak prostat karsinomunda ve en düşük olarak ta BPH’ta izlendi. Gruplar kendi içerisinde CD31 ve apoptotik indeks açısından karşılaştırıldığında, prostat karsinomunun hem PIN (p<0.001) hem de BPH’tan (p<0.001) anlamlı derecede yüksek olduğu izlendi. Laminin immunreaktivitesinin değerlendirilmesinde ise BPH ile PIN grupları arasında anlamlı bir fark yokken (p>0.05), prostat karsinomu hem PIN hem de BPH olgularından anlamlı derecede yüksek değerlere sahipti (p<0.001). Sonuç olarak, PİN’in PK ve BPH’dan ayrımında Ki-67, CD31 ve apoptotik indeksin faydalı olabileceği kanısına varıldı. Laminin’in ise PK’nun, BPH ve PİN olgularından ayrımında faydalı olabileceği fakat BPH ile PİN olgularının ayrımda aynı faydayı sağlamayacağı kanısına varıldı.

Histopathological And Immunohistochemical Evaluation Of The Proliferative Activity, Angiogenesis, Basement Membrane And Apoptosis In Benign, Premalignant And Malignant Lesions Of The Prostate

Prostate carcinoma (PC) is the most common malignancy among males and it is the second most common cause of death due to cancer (after lung cancer) in men. Prostatic intraepithelial neoplasia (PIN) is a premalignant lesion described recently. The differentiation of PIN from BPH or PC is important. In this study, it was aimed to investigate the place of Ki-67, CD31, Laminin immunoreactivities and apoptotic index in the differentiation of PIN (accepted as a precursor lesion of PC) from BPH or PC. A total of 150 specimens (50 PC, 50 PIN and 50 BPH cases) which were evaluated and diagnosed in the Department of Pathology, Medical Faculty, Ataturk University between 1991– 2001 were included in the study. Ki-67, CD31 and Laminin were applied to the paraffin sections with immunohistochemical method. Additionally H&E stained sections were prepared from paraffin blocks from the same cases for the evaluation of apoptotic index. The staining was accepted as positive for Ki-67 if dark-brown stained nucleus is present, for CD31 if cytoplasms of endothelial cells are stained, and for Laminin if continuous linear staining of basal membrane under the prostatic glandular epithelium is observed.Ki-67 immunoreactivity was the highest in PC group and the lowest in the BPH group. Moreover, while Ki-67immunoreactivity was significantly higher in PC group than in PIN group (p<0.001), the difference between PIN and BPH was p<0.05. Both CD31 immunoreactivity and apoptotoic index were found to be the highest in PC group and the lowest in BPH group. In the comparison of groups, PC group had higher CD31 immunoreactivity and apoptotic index values than in both PIN (p<0.001) and BPH (p<0.001) did. As a conclusion, it was suggested that Ki-67, CD31 immunoreactivities and apoptotic index were useful in the differentiation of PIN from BPH and PC. For Laminin, although it may be useful in the differentiation of PIN from PC, it cannot be used for PIN – BPH differentiation.

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  • Bostwick DG, McNeal JE. Pathology of the Prostat. London: W. B. Saunders Company; 1998:100.
  • Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225-49.
  • Brawer MK. Prostatic İntraeithelial Neoplasia: A Premalignant Lesion. Hum.Pathol. 1992;23:242-8.
  • Montironi R, Schulman CC. Precursors of Prostatic cancer. Progression and Chemoprevention. Eur Urol. 1996;30:133-7.
  • Qian J, Wollan P, Bostwick DG. The extend and multicentricity of high grade prostatic intraepithelial neoplasia in clinically localized prostatic adenocarcinoma. Hum Pathol. 1997;28: 143-8.
  • Galluzi CM, Loda M. Molecular events in the early Phases of prostate carcinogenesis. Eur Urol. 1996;30:167-76.
  • Myers RB, Grizzle WE. Biomarker expression in prostatic intraepithelial neoplasia. Eur Urol. 1996;30:153-66.
  • Maatta M, Virtanen I, Burgeson R, Harmainen HA. Comparative Analysis of the Distribution of Laminin Chains in the Basement Membranes in Some Malignant Epithelial Tumors: The α1 Chain of Laminin Shows a Selected Expression Pattern in Human Carcinomas. J Histochem Cytochem. 2001;49:711-26.
  • Cotron RS, Kumar V, Robins SL. Male genital system. In pathologic Basis of Disease 4th. Edition. Philadelphia: Sounders Company; 1989:1099-126.
  • Bostwick DG. Grading Prostate cancer. Am J Clin Pathol. 1994;102(suppl):38-56.
  • Bostwick DG, Qian J, Frankel K. The incidence of high grade prostatic intraepithelial neoplasia in needle biopsies. J Urol. 1995;154:1791-4.
  • Bostwick DG. Prospective origins of prostate carcinoma. Cancer. 1996;78:330-3.
  • Epstein JI, Wojno KJ. The prostate and seminal vesicles. In: Sternberg SS, Antonioly DA, Carter D, Mills SE, Oberman HA: Diagnostic Surgical Pathology. 3th edition. New York: 1999:1893-942.
  • Weinstein MH, Epstein J. Significance of High-Grade Prostatic Intraepithelial Neoplasia on Needle Biopsy. Hum Pathol. 1993;24:624-9.
  • Kendi S. Prostat ve Hastalıkları. Ankara: Haceettepe Üniversity; 1980:7-45.
  • Petersen RO. Prostate and seminal vesicle: Urologic Pathology, second Ed. Philadelphia: JB Lipincott Company; 1992:575.
  • Weinstein MH, Epstein J. Significiance of High-Grade Prostatic Intraepithelial Neoplasia on Needle Biopsy. Hum Pathol. 1993;24:624-9.
  • Emmert-Buck MR, Vocke CD, Pozzatti RO, et al. Allelic loss on chromosome 8p12-21 in microdissected prostatic intraepithelial neoplasia (PIN). Cancer Res. 1995;55:2959-62.
  • Sakr WA, Macoska JA, Benson P, et al. Allelic loss in locally metastatic multisampled prostate cancer. Cancer Res. 1994;15:3273-7.
  • Takahashi S, Qian J, Brown JA, et al. Potential markers of prostate cancer agressiveness detected by fluorescence in situ hybridization in needle biopsies. Cancer Res. 1994;54:3574- 9.
  • Taylor CR. The current role of immunohistochemistry in diagnostic pathology. In: Weinstein RS, Graham AR, Anderson RE, Benson ES, Cotron RS, Jarett C et al: Advances in Pathology and Laboratory Medicine. St.Luis: Mosby-Year Book Inc; 1994:59-105.
  • Gerdes J. An immunohistological method for estimating cell growth fractions in rapid histopathological diagnosis during surgery. Int J Cancer. 1984;35:1710-5. 23. Leong A.S, Wright J. The in tumor immunohistochemical Histopathology. 1987;11:1295-305. diagnosis.
  • Sadi MV, Barrack ER. Determination of growth fraction in advanced prostate cancer by Ki-67 immunostaining and its relationship to the time to tumor progression after hormonal therapy. Cancer. 1991;67:3065-71. 25.Claus S, Immunohistochemical proliferation rates in normal and benign hyperplastic human prostates. Urol Res. 1993;21:305-8. T, of age related
  • Colombel M, Vacherot F, Diez SG, Fontaine E, Buttyan R, Chopin D. Zonal variation of apoptozis and proliferation in the normal prostate and in benign prostatic hyperplasia. Br J Urol. 1998;82:380-5.
  • Fenely MR, Young MPA, Chinyama C, Kirby RS, Parkinson MC. Ki-67 expression in early prostate cancer and associated pathological lesions. J Cli Pathol. 1996;49:741-8.
  • Cotron RS, Kumar V, Robins SL. Male genital system: In Robins Pathology Basis of Disease. 5th.edition. Philadelphia: Sounders Company; 1998:1007-32.
  • Parkinson MC. Preneoplastik lesion of the prostate. Histopathology. 1995;27:301-11.
  • Meyer JS, Sufrin G, Martin SA. Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evalueted by thimidine labeling. J Urol. 1982;128:1353-6.
  • Gallee MPW, Jong EV, Kate FJWT, Schroder FH, Van Der Kwast TH. Monoclonal antibody Ki-67 defined growth fraction in benign prostatic hyperplasia and prostatic cancer. J Urol. 1989;142:1342-6.
  • Mc Loughlin J, Foster CS, Price P, Williams G, Abel PD. Evaluation of Ki-67 monoclonal antibody as prognostic indicator for prostatic carcinoma. Br J Urol. 1993;72:92-7.
  • Oomens EHGM, Van Steenbrugge GJ, Van Der Kwast TH, Schroder FH. Application of the monoclonal antibody Ki-67 on prostate biopsies to asses the proliferative cell fraction of human prostatic carcinoma. J Urol. 1991;145:81-5.
  • Raymond WA, Leong AS, Bolt JW, Milios J, Jose JS. Growth fractions in human prostatic carcinoma determined by Ki-67 immunostaining. J Pathol. 1988;156:161-7.
  • Tamboli P, Amin MB, Schultz DS, Linden MD, Kubus J. Comparative analysis of the nuclear proliferative index (Ki- 67) in benign prostate, prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Mod Pathol. 1996;9:1015-9.
  • Weinstein MH. Digital image analysis of proliferative index: Two distinc population of high grade prostatic intraepithelial neoplasia in close proximity to adenocarcinoma of the prostate. Hum Pathol. 1998;29:620-6.
  • Bigler SA, Deering RE, Brawer MK. Comparson of microskopik vascularity in benign and malignant prostate tissue. Hum Pathol. 1993;24:220-6.
  • Weidner N. Tumor Angiogenesis: review of current applications in tumor prognostication. Semin Diag Pathol. 1993;10:302-13.
  • Horak ER, Leek R, Leek N, et al. Angiogenesis assess by platelet/endothelialcell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet. 1992;340:1120-4.
  • Abulfia O, Triest WE, Adcock T, Sherer DM. The effect of Medroxyprogesterone acetat on angiogenesis in complex endometrial hyperplasia. Gynecol Oncol. 1999;72:193-8.
  • Montie JC. Current Prognostic Factors for Prostate Carcinoma. Cancer. 1996;78:341-4.
  • Kyprianou N, Tu H, Jacobs SC. Apoptotic versus proliferative activities in human benign prostatic hyperplasia. Hum Pathol. 1996;27:668-75.
  • Montironi R, Magi Galluzzi C, Scarpelli M, Giannulis I, Diamanti L. Occurrence of cell death (apoptozis) in prostatic intra-epithelial neoplasia. Virchows Arch A Pathol Anat Histopathol. 1993;423:351-7.
  • Epstein JI. The Evaluation of Radical Prostatectomy Specimens. Pathology Annual. 1991;26:159-210.
  • Haussler O, Epstein JI, Amin MB, Heitz PU, Hailemariam S. Cell proliferation, Apoptosis, oncogene, and tumor suppressor gene Status in adenosis with comparison to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and cancer. Hum Pathol. 1999;30:1077-86.
  • Sohn JH, Kim DH, Choi NG, Park YE, Ro JY. Caspase- 3/CPP32 immunoreactivity and its correlation with frequency of apoptotic bodies in human prostatic carcinomas and benign nodular hyperplasias. Histopathology. 2000;37:555-60.
  • Özer E, Canda T, Kurtoğlu B. The role of angiogenesis, laminin and CD44 expression in metastatic behavior of early- stage low-grade invasive breast carcinoma. Cancer. 1997;121:119-23.
  • Tawil NJ, Gowri V, Djoneidi M, Nip J, Carbonetto S, Brodt P. Integrin α3ß1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma. Int J Cancer. 1996;66:703-10.
  • Menard S, Bufalino R, Rile F, Cascinelli N, Veronesi U, Colaghi MI. Prognosis based on primary breast carcinoma instead of pathological nodal status. Br J Cancer. 1994;70:709- 12.
  • Maatta M, Virtanen I, Burgeson Rand Harmainen HA. Comparative Analysis of the Distribution of Laminin Chains in the Basement Membranes in Some Malignant Epithelial Tumors: The α1 Chain of Laminin Shows a Selected Expression Pattern in Human Carcinomas. J Histochem Cytochem. 2001;49:711-26.
  • Henning K, Berndt A, Katenkamp D, Kosmehl H. Loss of laminin-5 immunohistochemical marker of malignancy in epithelial lesion of the breast. Histopathology. 1999;34:305-9. an
  • Hindermann W, Berndt A, Haas KW, Wunderlich H, Katenkamp demonstration of the gamma 2 chain of laminin-5 in urinary bladder urothelial carcinoma. Impact of diagnosis and prognosis. Cancer Detect Prev. 2003;27:109-15.
Düzce Tıp Fakültesi Dergisi-Cover
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 1999
  • Yayıncı: Düzce Üniversitesi Tıp Fakültesi