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Increased Infiltration of Tumor Associated Macrophages is Associated With Poor Prognosis of Bladder Carcinoma In Situ After Intravesical Bacillus Calmette-Guerin Instillation

固有层 原位癌 医学 膀胱癌 病理 川地68 膀胱 巨噬细胞 癌症 免疫疗法 免疫组织化学 泌尿科 内科学 生物 体外 上皮 生物化学
作者
Hitoshi Takayama,Kazuo Nishimura,Akira Tsujimura,Yasutomo Nakai,Masashi Nakayama,Katsuyuki Aozasa,Äkïhïko Okuyama,Norio Nonomura
出处
期刊:The Journal of Urology [Lippincott Williams & Wilkins]
卷期号:181 (4): 1894-1900 被引量:122
标识
DOI:10.1016/j.juro.2008.11.090
摘要

No AccessJournal of UrologyInvestigative Urology1 Apr 2009Increased Infiltration of Tumor Associated Macrophages is Associated With Poor Prognosis of Bladder Carcinoma In Situ After Intravesical Bacillus Calmette-Guerin Instillationis accompanied byTumor Associated Macrophages: Predicting Bacillus Calmette-Guerin Immunotherapy Outcomesis companion ofOncological Followup After Radical Cystectomy for Bladder Cancer—Is There Any Benefit?Molecular Analyte Profiling of the Early Events and Tissue Conditioning Following Intravesical Bacillus Calmette-Guerin Therapy in Patients With Superficial Bladder CancerLong-Term Outcome of Simultaneous Transurethral Resection of Bladder Tumor and Prostate in Patients With Nonmuscle Invasive Bladder Tumor and Bladder Outlet Obstruction Hitoshi Takayama, Kazuo Nishimura, Akira Tsujimura, Yasutomo Nakai, Masashi Nakayama, Katsuyuki Aozasa, Akihiko Okuyama, and Norio Nonomura Hitoshi TakayamaHitoshi Takayama , Kazuo NishimuraKazuo Nishimura , Akira TsujimuraAkira Tsujimura , Yasutomo NakaiYasutomo Nakai , Masashi NakayamaMasashi Nakayama , Katsuyuki AozasaKatsuyuki Aozasa , Akihiko OkuyamaAkihiko Okuyama , and Norio NonomuraNorio Nonomura View All Author Informationhttps://doi.org/10.1016/j.juro.2008.11.090AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Tumor associated macrophages can regulate the growth of various cancers positively or negatively. Intravesical bacillus Calmette-Guerin instillation is now gold standard treatment for bladder carcinoma in situ. We investigated the correlation between tumor associated macrophages infiltrating bladder carcinoma in situ and the response to intravesical bacillus Calmette-Guerin therapy. Materials and Methods: We examined paraffin embedded tissues from 41 patients with bladder carcinoma in situ who received intravesical bacillus Calmette-Guerin therapy. Tumor associated macrophages were immunohistochemically stained by anti-CD68 monoclonal antibody. Results: The median number of tumor associated macrophages infiltrating among cancer cells and the number in the lamina propria were 4 and 24, respectively. Recurrent carcinoma in situ was found in 4.8% of cases with a lower cancer cell tumor associated macrophage count but in 47.6% of those with a higher cancer cell tumor associated macrophage count (less than 4 vs 4 or greater). Recurrence was found in 31.8% of patients with a lower lamina propria tumor associated macrophage count but in 21.1% of those with a higher lamina propria tumor associated macrophage count (less than 25 vs 25 or greater). The median ratio of tumor associated macrophages among cancer cells vs in the lamina propria was 0.2. Recurrence-free survival was significantly better in patients with a lower cancer cell tumor associated macrophage count (p = 0.0002). Those with a lower cancer cell-to-lamina propria tumor associated macrophage ratio had a higher recurrence-free rate (p <0.0001). Multivariate analysis revealed that the cancer cell tumor associated macrophage count and the cancer cell-to-lamina propria tumor associated macrophage ratio can be prognostic factors for bladder carcinoma in situ. Conclusions: The count of tumor associated macrophages infiltrating the cancer area is useful for predicting the response of bladder carcinoma in situ to intravesical bacillus Calmette-Guerin instillation before treatment initiation. References 1 : Histological study of vesical urothelium intervening between gross neoplasms in total cystectomy. J Urol1952; 68: 261. Link, Google Scholar 2 : Long-term results of intravesical therapy for superficial bladder cancer. Urol Clin North Am1992; 19: 573. Google Scholar 3 : A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional cell carcinoma of the bladder. N Engl J Med1991; 325: 1205. Google Scholar 4 : The use of bacillus Calmette-Guerin in the therapy of bladder carcinoma in situ. J Urol1985; 137: 36. Google Scholar 5 : The limits of bacillus Calmette-Guerin for carcinoma in situ of the bladder. J Urol2001; 165: 745. Link, Google Scholar 6 : Bladder carcinoma in situ in 2003: state of the art. Eur Urol2004; 45: 142. Google Scholar 7 : Urinary cytokines during intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: processing, stability and prognostic value. J Urol1996; 155: 477. Link, Google Scholar 8 : Interleukin-8 expression in the urine after bacillus Calmette-Guerin therapy: a potential prognostic factor of tumor recurrence and progression. J Urol1997; 158: 1340. Link, Google Scholar 9 : Prognosis of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer by immunological urinary measurements: statistically weighted syndrome analysis. J Urol1998; 159: 1054. Link, Google Scholar 10 : T helper 1/2 lymphocyte urinary cytokine profiles in responding and nonresponding patients after 1 and 2 courses of bacillus Calmette-Guerin for superficial bladder cancer. J Urol2001; 166: 2142. Link, Google Scholar 11 : The origin and function of tumor-associated macrophages. Immunol Today1992; 13: 265. Google Scholar 12 : Inflammation and cancer: back to Virchow?. Lancet2001; 357: 539. Google Scholar 13 : Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer2006; 42: 717. Google Scholar 14 : Tumor-associated macrophage as target for cancer therapy. J Natl Cancer Inst1998; 90: 1583. Google Scholar 15 : Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res1996; 6: 4625. Google Scholar 16 : Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol2005; 35: 8959. Google Scholar 17 : Prognostic value of tumor-associated macrophage count in human bladder cancer. Int J Urol2000; 7: 263. Google Scholar 18 : Prognostic significance of endothelial Per-ARNT-Sim domain protein 1/hypoxia-inducible factor-2α expression in a subset of tumor associated macrophages in invasive bladder cancer. J Urol2004; 171: 1080. Link, Google Scholar 19 : Role of IL-12 in the induction and potentiation of IFN-gamma in response to bacille Calmette-Guérin. J Immunol1999; 163: 4246. Google Scholar 20 : Intravesical bacille Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of bacille Calmette-Guérin. Cancer Res1987; 47: 1762. Google Scholar Departments of Urology and Pathology (KA), Osaka University Graduate School of Medicine, Suita, Japan© 2009 by American Urological AssociationFiguresReferencesRelatedDetailsRelated articlesJournal of Urology23 Feb 2009Tumor Associated Macrophages: Predicting Bacillus Calmette-Guerin Immunotherapy OutcomesJournal of Urology23 Feb 2009Oncological Followup After Radical Cystectomy for Bladder Cancer—Is There Any Benefit?Journal of Urology23 Feb 2009Molecular Analyte Profiling of the Early Events and Tissue Conditioning Following Intravesical Bacillus Calmette-Guerin Therapy in Patients With Superficial Bladder CancerJournal of Urology23 Feb 2009Long-Term Outcome of Simultaneous Transurethral Resection of Bladder Tumor and Prostate in Patients With Nonmuscle Invasive Bladder Tumor and Bladder Outlet Obstruction Volume 181Issue 4April 2009Page: 1894-1900 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordsurinary bladdermacrophagesprognosisBCG vaccinecarcinoma in situMetricsAuthor Information Hitoshi Takayama More articles by this author Kazuo Nishimura More articles by this author Akira Tsujimura More articles by this author Yasutomo Nakai More articles by this author Masashi Nakayama More articles by this author Katsuyuki Aozasa More articles by this author Akihiko Okuyama More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF downloadLoading ...
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