Immunohistochemical Expression of Ki-67 Antigen, Cox-2 and Bax/Bcl-2 in Prostate Cancer; Prognostic Value in Biopsies and Radical Prostatectomy Specimens

Rubio, José; Ramos, David; Löpez‐Guerrero, José Antonio; Iborra, I.; Collado, A.; Solsona, E.; Almenar, S.; Llombart‐Bosch, Antonio

doi:10.1016/j.eururo.2005.06.014

Cited by 88 publications

(66 citation statements)

References 18 publications

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“…38 Earlier studies on immunohistochemistry localization and semiquantitative estimation of COX-2 expression concluded that COX-2 expression has limited association with stage and disease severity (local invasion) but it strongly associates with tumor grade. [10][11][12][13][14][15] On contrary, some reports have dismissed any association with tumor grade and have suggested that COX-2 is expressed by infiltrating lymphocytes and macrophage, which occurs during inflammatory atrophy of the prostate. 27 However, none of these reports analyzed COX-2 expression with respect to biochemical recurrence (i.e., disease progression).…”

Section: Determination Of Sensitivity Specificity Accuracy Ppv Andmentioning

confidence: 99%

“…[10][11][12] Typically, later studies reported low or no expression in normal, benign prostatic hyperplasia or low-grade cancer tissues but elevated levels in prostatic intraepithelial neoplasia (PIN) and high-grade cancer. [13][14][15][16][17][18][19][20][21][22][23][24][25][26] A prominent study, however, discounted COX-2 specific staining in all epithelial tissues and claimed that COX-2 is expressed only in infiltrating lymphocytes and proliferative inflammatory atrophy. 27 Nonetheless, several studies, using experimental models and established prostate cancer cell lines, have established a chemopreventive and antitumor activity of COX-2 inhibitors, implying the putative role of COX-2 in prostate carcinogenesis.…”

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confidence: 99%

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Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

Cohen

Gómez

Omori

et al. 2006

Intl Journal of Cancer

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Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n 5 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twentythree patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high-or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p 5 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process. ' 2006 Wiley-Liss, Inc.Key words: inflammation; immunohistochemistry; PSA; cancer progression; prognostic indicators; multivariate analysis; tumor markers Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are prostaglandin endoperoxide synthases, which are rate limiting enzymes in the conversion of the fatty acid arachidonic acid into physiologically active eicosanoids such as prostaglandin, thromboxane and prostacyclin. 1 COX-2 is the inducible form of COX that is frequently elevated in cancer tissues. [2][3][4] Although the mechanism of COX-2 action in carcinogenesis or progression is not well established, COX-2 inhibitors have been shown to be chemopreventive in cancer, specifically in colorectal cancer. [5][6][7] The expression and role of COX-2 in prostate cancer has been a topic of several reports over the decade. 8,9 There exists some controversy over the expression, detection and the putative role of COX-2 in prostate carcinogenesis and progression. While early studies reported high-level expression of COX-2 in prostate, findings from subsequent studies have been mixed. [10][11][12] Typically, later studies reported low or no expression in normal, benign prostatic hyperplasi...

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Section: Determination Of Sensitivity Specificity Accuracy Ppv Andmentioning

confidence: 99%

mentioning

confidence: 99%

Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

Cohen

Gómez

Omori

et al. 2006

Intl Journal of Cancer

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“…Ki67, a proliferation marker, is strongly associated with the biological behavior of prostate cancer (22). Many studies have demonstrated the independent prognostic value of Ki67 staining both in clinically localized disease treated by radical prostatectomy (23)or radiation (18,24,25), and in patients with advanced disease (25,26). Most recently, Gunia et al (26) reported that Ki67 SI >5% is an independent predictor of biochemical recurrence following radical prostatectomy.…”

Section: Discussionmentioning

confidence: 99%

101 Increased Cancer Cell Proliferation in Prostate Cancer Patients With High Levels of Serum Folate

Tomaszewski¹,

Cummings²,

Parwani³

et al. 2010

Journal of Urology

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Background-A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). As tumor cells in culture proliferate directly in response to available folic acid, the goal of our study was to determine if there is a similar relationship between patient folate status, and the proliferative capacity of tumors in men with prostate cancer.

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“…Индекс Ki-67, определяемый как отношение количества клеток с интенсивной ядерной реакцией на Ki-67 к общему числу кле-ток, является независимым показателем прогно-за рецидива и выживаемости у больных РПЖ. [7,8].…”

Section: Application Immunohistochemically Researchunclassified

Application Immunohistochemically Research Methods in the Diagnosis of Prostate Cancer

Пульбере¹,

Бабиченко²,

Котов³

et al. 2017

Vestn. urol.

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581-46-47; e-mail: pulpiv@mail.ru Введение. Актуальной проблемой современной урологии остается дифференциальная диагности-ка различных болезней предстательной железы.Цель исследования. Повышение эффективности дифференциальной диагностики заболеваний предстательной железы.Материалы и методы. В биоптатах пациентов с доброкачественной гиперплазией предстательной железы (ДГПЖ) и раком предстательной железы (РПЖ) проведено иммуногистохимическое исследова-ние продукции маркера пролиферации Ki-67, матриксной металлопротеиназы-9, ингибитора матрикс-ной металлопротеиназы-TIMP-1 и распределение коллагена IV типа.Результаты. Выявлена умеренная положительная корреляция между градацией по шкале Глисона и индексом пролиферации клеток по показателю Ki 67 (rs =0,674) и умеренная отрицательная корреля-ция градации по шкале Глисона с уровнем продукции матриксной металлопротеиназы-9 (rs= -0,660). Слабая достоверная отрицательная корреляция установлена между уровнем пролиферативной актив-ности клеток ипродукцией опухолевыми клетками MMП-9 (rs= -0,369). Выявлено достоверное сниже-ние уровня MMP-9 и TIMP-1 в аденокарциноме различной градации. Инвазивные свойства опухолевых клеток, выражающиеся в разрушении коллагена IVтипа базальной мембраны и соединительно-ткан-ной стромы простаты, опосредованы дисбалансом между MMП-9 и белком, блокирующим этот фер-мент -TIMP-1, продукция которого снижается в аденокарциномах различной градации, по сравнению с ДГПЖ.Выводы: ДГПЖ характеризуется высокой продукцией ММП 9 типа, разрушающей коллаген ба-зальных мембран и стромы, протеолитическое действие которой блокируется высоким содержанием TIMP-1. В опухолях продукция ММП 9 типа снижена, разрушение коллагена IV происходит на фоне резкого снижения продукции TIMP-1.Ключевые слова: аденокарцинома предстательной железы, MMP-9, TIMP-1, Ki-67, коллаген IV типа 581-46-47; e-mail: pulpiv@mail.ru Introduction. The actual problem of modern urology remains differential diagnostics of various diseases of the prostate gland.The purpose of the study. Increasing the effectiveness of differential diagnosis of diseases of the prostate. Materials and methods. In the biopsy specimens of patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa), an immunohistochemical study of the production of the Ki-67 proliferation marker, matrix metalloproteinase-9, the matrix metalloproteinase inhibitor TIMP-1, and the distribution of collagen type IV was performed.Results. A moderate positive correlation was found between Gleason gradation and the cell proliferation index for Ki 67 (rs = 0.674) and a moderate negative correlation of Gleason gradation with the level of production of matrix metalloproteinase-9 (rs = -0.660). A weak significant negative correlation was established between the level of proliferative cell activity and the production of MMP-9 tumor cells (rs = -0.369). A significant decrease in the level of MMP-9 and TIMP-1 in adenocarcinoma of different grades was revealed. The invasive properties of tumor cells, expressed in the destruction of ...

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Immunohistochemical Expression of Ki-67 Antigen, Cox-2 and Bax/Bcl-2 in Prostate Cancer; Prognostic Value in Biopsies and Radical Prostatectomy Specimens

Cited by 88 publications

References 18 publications

Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

101 Increased Cancer Cell Proliferation in Prostate Cancer Patients With High Levels of Serum Folate

Application Immunohistochemically Research Methods in the Diagnosis of Prostate Cancer

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