Background Management of high risk prostate cancer (HRPC) is in evolving stage. Effectiveness of the various treatment strategies is being explored. We examined the short term efficacy of laparoscopic radical prostatectomy (LRP) in treatment of patients with HRPC. Methods Retrospective observational study had 140 HRPC patients of Indian origin, based on D’Amico classification system. Baseline workup was completed. Perioperative parameters and pathological findings were recorded. Multivariate analysis was performed to find predictive factors of pathological stage and PSM. 5 year biochemical recurrence free survival (BCRFS), cancer specific survival (CSS) and overall survival (OS) were calculated. Results Mean age and PSA were 67.24±7.37 years and 23.29 ng/ml respectively. Three fourth of patients had a biopsy GS ≥8. 53.6% of patients were of clinical stage (CS) ≤T2; while 46.4% were of stage ≥T3. Conversion to open surgery rate was 15%. Mean operative time was 210 minutes; blood loss 230 ml; hospital stay 3 days; catheterization time 14 days; grade II or more complication rate 22.1%; LN positivity 20.0%; PSM rate 25.7%; upstaging 35.7%; down-staging 14.3%; pT2 31.4%; pT3a 26.4%; pT3b 42.2%. GS and CS were predictive of pathological stage and PSM respectively. 89.3% of cases were continent postoperatively. 5 year BCRFS, CSS and OS were 68.3%, 89.2% and 78.7% respectively. Conclusions LRP is feasible and effective initial treatment for HRPC. Perioperative morbidity is acceptable. Accurate staging helps in better planning of the adjuvant therapy. Good short term survival can be achieved with multimodal therapy.
{"title":"Short Term Outcomes in Indian Patients with High Risk Prostate Cancer after Laparoscopic Radical Prostatectomy- Data from a Single Institute","authors":"P. Patel, Shrenik J. Shah, Arpan Choudhary","doi":"10.32948/AUO.2020.09.29","DOIUrl":"https://doi.org/10.32948/AUO.2020.09.29","url":null,"abstract":"Background Management of high risk prostate cancer (HRPC) is in evolving stage. Effectiveness of the various treatment strategies is being explored. We examined the short term efficacy of laparoscopic radical prostatectomy (LRP) in treatment of patients with HRPC.\u0000Methods Retrospective observational study had 140 HRPC patients of Indian origin, based on D’Amico classification system. Baseline workup was completed. Perioperative parameters and pathological findings were recorded. Multivariate analysis was performed to find predictive factors of pathological stage and PSM. 5 year biochemical recurrence free survival (BCRFS), cancer specific survival (CSS) and overall survival (OS) were calculated. \u0000Results Mean age and PSA were 67.24±7.37 years and 23.29 ng/ml respectively. Three fourth of patients had a biopsy GS ≥8. 53.6% of patients were of clinical stage (CS) ≤T2; while 46.4% were of stage ≥T3. Conversion to open surgery rate was 15%. Mean operative time was 210 minutes; blood loss 230 ml; hospital stay 3 days; catheterization time 14 days; grade II or more complication rate 22.1%; LN positivity 20.0%; PSM rate 25.7%; upstaging 35.7%; down-staging 14.3%; pT2 31.4%; pT3a 26.4%; pT3b 42.2%. GS and CS were predictive of pathological stage and PSM respectively. 89.3% of cases were continent postoperatively. 5 year BCRFS, CSS and OS were 68.3%, 89.2% and 78.7% respectively. \u0000Conclusions LRP is feasible and effective initial treatment for HRPC. Perioperative morbidity is acceptable. Accurate staging helps in better planning of the adjuvant therapy. Good short term survival can be achieved with multimodal therapy.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45592863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prostate cancer is one of the most common uro-oncological disease in men and is globally leading cause of cancer related deaths in males. The somatic mutation has a strong link in the occurrence of cancer. Mutation in the oncogenes and tumor suppressor genes that alter key cellular functions can lead to prostate cancer initiation and progression. Whole genome sequencing has identified numerous genetic alternations and further provided a detail view of the mutations in genes that drive progression of prostate cancer. TP53, SPOP, PTEN, ATM, AR, CTNNB1, FOXA1, KMT2D, BRACA2 and APC were found as frequently mutated genes in prostate cancer. Using data from cBioPortal and PubMed, this review summarizes the status and possible impact of mutations in these driver genes on survival, progression, and metastasis of prostate cancer. This study will contribute a better understanding of biological basis for clinical variability in prostate cancer patients and may provide new genetic diagnostic markers and drug targets.
{"title":"Mutations in Cancer Driver Genes: An Insight into Prostate Cancer Progression","authors":"S. Prasad, S. Srivastava","doi":"10.32948/auo.2019.09.12","DOIUrl":"https://doi.org/10.32948/auo.2019.09.12","url":null,"abstract":"Prostate cancer is one of the most common uro-oncological disease in men and is globally leading cause of cancer related deaths in males. The somatic mutation has a strong link in the occurrence of cancer. Mutation in the oncogenes and tumor suppressor genes that alter key cellular functions can lead to prostate cancer initiation and progression. Whole genome sequencing has identified numerous genetic alternations and further provided a detail view of the mutations in genes that drive progression of prostate cancer. TP53, SPOP, PTEN, ATM, AR, CTNNB1, FOXA1, KMT2D, BRACA2 and APC were found as frequently mutated genes in prostate cancer. Using data from cBioPortal and PubMed, this review summarizes the status and possible impact of mutations in these driver genes on survival, progression, and metastasis of prostate cancer. This study will contribute a better understanding of biological basis for clinical variability in prostate cancer patients and may provide new genetic diagnostic markers and drug targets.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48386616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sabeeh-ur-Rehman Butt, M. S. Khan, C. Murias, Maria Reyes Gonzalez-Exposito, H. Arkenau, A. Patrikidou
As research focus in oncology has recently shifted to immunomodulation, the era of introduction of immunotherapeutic agents in the management of prostate cancer has just begun. With the success of checkpoint blockade drugs in certain advanced tumours, ongoing efforts are aimed at identification and validation of new actionable immune targets to consolidate and expand the initial success in other tumour types. In this paper, we review the immunotherapy research in the management of prostate cancer to date, as well as the various emerging immunotherapeutic agents and their possible use. Although monotherapy has thus far had disappointing results in prostate cancer, promising combination strategies are under evaluation.
{"title":"Immunotherapy Landscape in Prostate Cancer: Successes, Failures and Promises","authors":"Sabeeh-ur-Rehman Butt, M. S. Khan, C. Murias, Maria Reyes Gonzalez-Exposito, H. Arkenau, A. Patrikidou","doi":"10.32948/auo.2019.09.04","DOIUrl":"https://doi.org/10.32948/auo.2019.09.04","url":null,"abstract":"As research focus in oncology has recently shifted to immunomodulation, the era of introduction of immunotherapeutic agents in the management of prostate cancer has just begun. With the success of checkpoint blockade drugs in certain advanced tumours, ongoing efforts are aimed at identification and validation of new actionable immune targets to consolidate and expand the initial success in other tumour types. In this paper, we review the immunotherapy research in the management of prostate cancer to date, as well as the various emerging immunotherapeutic agents and their possible use. Although monotherapy has thus far had disappointing results in prostate cancer, promising combination strategies are under evaluation.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44385872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The 2016 WHO classification of tumors of the urothelial tract recently revised the classification of invasive urothelial carcinoma to include nested, microcystic, micropapillary, plasmacytoid, sarcomatoid, giant cell, and poorly differentiated variants, among others. In particular, invasive micropapillary carcinoma (IMPC) is now recognized as a distinct entity with aggressive features, including higher-stage disease, invasive features, and poorer response to intravesical chemotherapy. In this review, we highlight recent studies that further characterize the histopathology, immunohistochemistry, molecular mechanisms, and clinical implications of a diagnosis of IMPC. Because the correct morphologic diagnosis of IMPC is critical in terms of clinical management, we explore the diagnostic criteria of IMPC and differential diagnosis of urothelial IMPC from non-urothelial sites, highlighting studies that examine both traditional urothelial immunohistochemical markers as well as novel markers. We highlight recent advances in the molecular sub-categorization of IMPC, and review the differences compared to other forms of urothelial carcinoma. Optimal management of patients with IMPC is still unclear, although early cystectomy, regardless of pathologic stages, is recommended. We also highlight several studies that address the clinical challenges as well as current treatment protocols for IMPC.
{"title":"Micropapillary Carcinoma of the Bladder: Recent Advances","authors":"Jim Hsu, J. Ro","doi":"10.32948/AUO.2019.07.01","DOIUrl":"https://doi.org/10.32948/AUO.2019.07.01","url":null,"abstract":"The 2016 WHO classification of tumors of the urothelial tract recently revised the classification of invasive urothelial carcinoma to include nested, microcystic, micropapillary, plasmacytoid, sarcomatoid, giant cell, and poorly differentiated variants, among others. In particular, invasive micropapillary carcinoma (IMPC) is now recognized as a distinct entity with aggressive features, including higher-stage disease, invasive features, and poorer response to intravesical chemotherapy. In this review, we highlight recent studies that further characterize the histopathology, immunohistochemistry, molecular mechanisms, and clinical implications of a diagnosis of IMPC. Because the correct morphologic diagnosis of IMPC is critical in terms of clinical management, we explore the diagnostic criteria of IMPC and differential diagnosis of urothelial IMPC from non-urothelial sites, highlighting studies that examine both traditional urothelial immunohistochemical markers as well as novel markers. We highlight recent advances in the molecular sub-categorization of IMPC, and review the differences compared to other forms of urothelial carcinoma. Optimal management of patients with IMPC is still unclear, although early cystectomy, regardless of pathologic stages, is recommended. We also highlight several studies that address the clinical challenges as well as current treatment protocols for IMPC.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46710880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Krishna, S. Krishnamoorthy, H. Sekar, S. Murali, R. Swaminathan, N. Kumaresan
Immunoglobulin G4 related disease (IgG4-RD) is a systemic fibro inflammatory condition that usually presents with multiorgan involvement. We present a rare case of 54 year old male with an isolated IgG4-RD of epididymis. The patient presented with a progressive swelling of the left testicle. A clinical diagnosis of tuberculosis was made. Ultrasound scrotum showed a relatively hetero-echoic mass lesion involving the left epididymis in close proximity to the left testis. There was a focal spindle cell proliferation and an increase in number of plasma cells and keloid like collagen. Immunohistochemistry was positive for vimentin and IgG4 and negative for CD34. Serum level of IgG4 was elevated (165 mg per dL). Computed tomography of abdomen and thorax did not show any systemic involvement. HE was posted for excision of the epididymal mass. Intraoperatively, the mass was found to be densely adherent to left testicle and inseparable from it, necessitating left total orchiectomy. Histopathology and immunohistochemistry with elevated serum IgG4 levels confirmed the diagnosis of IgG4-RD of the epididymis. To the best of our knowledge, this condition is an extremely rare entity, with only very few cases of isolated IgG4-RD of epididymis reported in medical literature, with no other systemic manifestations.
{"title":"IgG4 Related Disease of Epididymis, Mimicking Testicular Malignancy – A Rare Entity","authors":"L. Krishna, S. Krishnamoorthy, H. Sekar, S. Murali, R. Swaminathan, N. Kumaresan","doi":"10.32948/AUO.2019.04.26","DOIUrl":"https://doi.org/10.32948/AUO.2019.04.26","url":null,"abstract":"Immunoglobulin G4 related disease (IgG4-RD) is a systemic fibro inflammatory condition that usually presents with multiorgan involvement. We present a rare case of 54 year old male with an isolated IgG4-RD of epididymis. The patient presented with a progressive swelling of the left testicle. A clinical diagnosis of tuberculosis was made. Ultrasound scrotum showed a relatively hetero-echoic mass lesion involving the left epididymis in close proximity to the left testis. There was a focal spindle cell proliferation and an increase in number of plasma cells and keloid like collagen. Immunohistochemistry was positive for vimentin and IgG4 and negative for CD34. Serum level of IgG4 was elevated (165 mg per dL). Computed tomography of abdomen and thorax did not show any systemic involvement. HE was posted for excision of the epididymal mass. Intraoperatively, the mass was found to be densely adherent to left testicle and inseparable from it, necessitating left total orchiectomy. Histopathology and immunohistochemistry with elevated serum IgG4 levels confirmed the diagnosis of IgG4-RD of the epididymis. To the best of our knowledge, this condition is an extremely rare entity, with only very few cases of isolated IgG4-RD of epididymis reported in medical literature, with no other systemic manifestations.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49223132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renal cell carcinoma (RCC) is one of the most devastating disease with higher mortality rates. It comprises several subtypes exhibiting distinct histological features and clinical staging. Despite recent advancement in understanding the biology of RCC success in treatment rates remains dismal. This may be partly due to lack of specific biomarkers for early detection/prognosis and poor clinical outcome. Noncoding protein transcripts in the genome play important role in the initiation, evolution and progression of cancer. With the advancement in genomic analysis techniques, especially next-generation sequencing, a large number of new transcripts have been discovered, leading to better understanding of coding and noncoding RNAs. In the present review, we summarize recent advancement on renal cancer associated noncoding RNAs which includes long noncoding RNAs, microRNAs, and circular RNAs for their involvement in RCC along with their clinical implication as prognostic and diagnosis biomarkers.
{"title":"Noncoding RNAs and Its Implication as Biomarkers in Renal Cell Carcinoma: A Systematic Analysis","authors":"Shiv Verma, Sanjay Gupta","doi":"10.32948/AUO.2019.03.28","DOIUrl":"https://doi.org/10.32948/AUO.2019.03.28","url":null,"abstract":"Renal cell carcinoma (RCC) is one of the most devastating disease with higher mortality rates. It comprises several subtypes exhibiting distinct histological features and clinical staging. Despite recent advancement in understanding the biology of RCC success in treatment rates remains dismal. This may be partly due to lack of specific biomarkers for early detection/prognosis and poor clinical outcome. Noncoding protein transcripts in the genome play important role in the initiation, evolution and progression of cancer. With the advancement in genomic analysis techniques, especially next-generation sequencing, a large number of new transcripts have been discovered, leading to better understanding of coding and noncoding RNAs. In the present review, we summarize recent advancement on renal cancer associated noncoding RNAs which includes long noncoding RNAs, microRNAs, and circular RNAs for their involvement in RCC along with their clinical implication as prognostic and diagnosis biomarkers.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44846110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ovarian-type epithelial tumors rarely occur in the human testis and paratesticular region. Histologically, these tumors closely resemble their ovarian counterparts and are therefore classified similarly to ovarian epithelial tumors. Most reported ovarian-type tumor cases are serous tumors, but the full spectrum of ovarian neoplasms has been described, including mucinous, endometrioid, clear cell, and Brenner tumors. In this review, we describe the clinical, morphologic, and immunohistochemical features of Mullerian-type epithelial tumors seen in the testis, with an emphasis on comparison with ovarian tumors. We also discuss theories of pathogenesis, considerations in the differential diagnosis, and recent advances in molecular characterization and therapeutic modalities.
{"title":"Ovarian-type Tumors (Mullerian Tumors) of the Testis: Clinicopathologic Findings with Recent Advances","authors":"Michelle Lin, A. Ayala, J. Ro","doi":"10.32948/AUO.2019.03.07","DOIUrl":"https://doi.org/10.32948/AUO.2019.03.07","url":null,"abstract":"Ovarian-type epithelial tumors rarely occur in the human testis and paratesticular region. Histologically, these tumors closely resemble their ovarian counterparts and are therefore classified similarly to ovarian epithelial tumors. Most reported ovarian-type tumor cases are serous tumors, but the full spectrum of ovarian neoplasms has been described, including mucinous, endometrioid, clear cell, and Brenner tumors. In this review, we describe the clinical, morphologic, and immunohistochemical features of Mullerian-type epithelial tumors seen in the testis, with an emphasis on comparison with ovarian tumors. We also discuss theories of pathogenesis, considerations in the differential diagnosis, and recent advances in molecular characterization and therapeutic modalities.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45597059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Gleason grading system for prostatic carcinoma is widely used internationally and is based on microscopic architectural patterns of tumors. Over the years, there have been modifications to the original grading system established by Donald F Gleason in 1966 and refined in 1974 which have subsequently been established by the World Health Organization in its WHO Classification of Tumors of the Urinary System and Male Genital Organs book, published in 2016. There have been certain practical issues associated with the changes, of note, the addition of intraductal carcinoma of prostate (IDC-P), which unlike its breast counterpart rarely occurs in isolation without association with invasive carcinoma and tends to be associated with high-grade invasive carcinoma. In addition, the Grade group system has been introduced which categorizes tumors into prognostically relevant groups based on the histological grade scores. The grade group system brings to light the importance of making accurate scoring and subsequent grouping of the tumors as it affects the clinical treatment, prognostic implication and stage assignment. Molecular pathology of the prostate is not widely utilized in clinical practice, but is emerging. The most common genomic aberration in prostate cancer includes gene fusion, amplification, deletion, and mutation. In addition, up and down regulation of gene expression in critical cellular pathways is also at play. A series of long noncoding RNA expression changes have been also unveiled from transcriptome sequencing data. They play a regulatory role in prostate cancer and are promising diagnostic and potentially prognostic markers as well as molecular treatment strategy. In this review, we summarize recent advances in molecular pathology of prostate cancer and their emerging clinical utility with currently available molecular tests. In this review article, we discuss the followings: 1) Gleason grading system with its modification, 2) Grade group, 3) Intraductal carcinoma, and 4) molecular pathology. Additionally, we present that molecular studies continue to emerge, and there is significant opportunity for targeted therapeutic options that remains to be explored in depth.
国际上广泛使用的前列腺癌Gleason分级系统是基于肿瘤的显微结构模式。多年来，对Donald F Gleason于1966年建立并于1974年完善的原始分级系统进行了修改，随后由世界卫生组织在2016年出版的《WHO泌尿系统和男性生殖器官肿瘤分类》一书中建立。与这些变化相关的一些实际问题，值得注意的是，前列腺导管内癌(IDC-P)的增加，与乳腺导管内癌不同，它很少单独发生，与浸润性癌无关，往往与高级别浸润性癌有关。此外，还引入了分级分组系统，根据组织学分级评分将肿瘤分为与预后相关的组。分级分组系统揭示了对肿瘤进行准确评分和后续分组的重要性，因为它影响临床治疗、预后意义和分期分配。前列腺分子病理学尚未广泛应用于临床实践，但正在兴起。前列腺癌中最常见的基因组畸变包括基因融合、扩增、缺失和突变。此外，关键细胞通路中基因表达的上下调节也在起作用。转录组测序数据也揭示了一系列长链非编码RNA的表达变化。它们在前列腺癌中起调节作用，是有希望的诊断和潜在的预后标记以及分子治疗策略。在这篇综述中，我们总结了前列腺癌分子病理学的最新进展及其在目前可用的分子检测中的临床应用。本文就以下内容作一综述:1)Gleason分级系统及其改进;2)分级组;3)导管内癌;4)分子病理学。此外，我们认为分子研究不断涌现，有针对性的治疗选择的重大机会仍有待深入探索。
{"title":"Intraductal Carcinoma of Prostate (IDC-P), Grade Group, and Molecular Pathology: Recent Advances and Practical Implication","authors":"Ashwyna Sunassee, G. A. Sannaa, J. Ro","doi":"10.32948/AUO.2019.03.11","DOIUrl":"https://doi.org/10.32948/AUO.2019.03.11","url":null,"abstract":"The Gleason grading system for prostatic carcinoma is widely used internationally and is based on microscopic architectural patterns of tumors. Over the years, there have been modifications to the original grading system established by Donald F Gleason in 1966 and refined in 1974 which have subsequently been established by the World Health Organization in its WHO Classification of Tumors of the Urinary System and Male Genital Organs book, published in 2016. There have been certain practical issues associated with the changes, of note, the addition of intraductal carcinoma of prostate (IDC-P), which unlike its breast counterpart rarely occurs in isolation without association with invasive carcinoma and tends to be associated with high-grade invasive carcinoma. In addition, the Grade group system has been introduced which categorizes tumors into prognostically relevant groups based on the histological grade scores. The grade group system brings to light the importance of making accurate scoring and subsequent grouping of the tumors as it affects the clinical treatment, prognostic implication and stage assignment. Molecular pathology of the prostate is not widely utilized in clinical practice, but is emerging. The most common genomic aberration in prostate cancer includes gene fusion, amplification, deletion, and mutation. In addition, up and down regulation of gene expression in critical cellular pathways is also at play. A series of long noncoding RNA expression changes have been also unveiled from transcriptome sequencing data. They play a regulatory role in prostate cancer and are promising diagnostic and potentially prognostic markers as well as molecular treatment strategy. In this review, we summarize recent advances in molecular pathology of prostate cancer and their emerging clinical utility with currently available molecular tests. In this review article, we discuss the followings: 1) Gleason grading system with its modification, 2) Grade group, 3) Intraductal carcinoma, and 4) molecular pathology. Additionally, we present that molecular studies continue to emerge, and there is significant opportunity for targeted therapeutic options that remains to be explored in depth.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41734764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) was first discovered in 1987 and confirmed to be a protein that is mainly expressed on the surface of activated lymphocytes. CTLA-4 is expressed on the surface of T cells and binds to B7 expressed on antigen presenting cells(APCs) to potentially play a role in inhibiting lymphocyte proliferation. Inhibitors of CTLA-4 were developed to promote the anti-tumor effects of T cells and inhibit tumor growth. CTLA-4, as an immune checkpoint, has been realized as an important therapeutic target in bladder cancer. Two main CTLA-4 inhibitors are currently used: ipilimumab is a first-generation IgG1 monoclonal antibody that targets CTLA-4, and it is completely synthetic; tremelimumab, representing another class of CTLA-4 inhibitors, is a monoclonal antibody against CTLA-4 that acts similarly to ipilimumab and binds specifically to CTLA-4. The two types of CTLA-4 inhibitors were found to improve the treatment effect in patients with bladder cancer in comparison to conventional agents. To review this topic, we searched recently published related articles.
{"title":"Progress in Research on Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) and Bladder Cancer","authors":"W. Fang, Chun Chen","doi":"10.32948/AUO.2019.01.22","DOIUrl":"https://doi.org/10.32948/AUO.2019.01.22","url":null,"abstract":"Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) was first discovered in\u00001987 and confirmed to be a protein that is mainly expressed on the surface of activated\u0000lymphocytes. CTLA-4 is expressed on the surface of T cells and binds to B7 expressed on antigen presenting cells(APCs) to potentially play a role in inhibiting lymphocyte proliferation. Inhibitors of CTLA-4 were developed to promote the anti-tumor effects of T cells and inhibit tumor growth. CTLA-4, as an immune checkpoint, has been realized as an important therapeutic target in bladder cancer. Two main CTLA-4 inhibitors are currently used: ipilimumab is a first-generation IgG1 monoclonal antibody that targets CTLA-4, and it is completely synthetic; tremelimumab, representing another class of CTLA-4 inhibitors, is a monoclonal antibody against CTLA-4 that acts similarly to ipilimumab and binds specifically to CTLA-4. The two types of CTLA-4 inhibitors were found to improve the treatment effect in patients with bladder cancer in comparison to conventional agents. To review this topic, we searched recently published related articles.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46741435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose To investigate the role of chronic inflammation in prostatic carcinogenesis with an emphasis on cancers of grade group 2 or above. Methods The presence/absence and extent of chronic inflammation and other relevant pathological findings were assessed using prostate needle biopsies obtained from patients with clinical parameters with suspicion of malignancy. In patients with no prior prostate cancer, follow-up biopsies were reviewed and correlated with the initial pathological findings. Results Of 1,006 prostate needle biopsy cases accessioned over 3 years at our institution, the initial biopsies of 244 cases were identified with no evidence of prostate cancer. These cases were divided into two subsets, including 202 cases with and 42 without chronic inflammation. Pathological findings assessed in this subset included post-atrophic hyperplasia, proliferative inflammatory atrophy, and high-grade prostatic intraepithelial neoplasia (HGPIN). Post-atrophic hyperplasia and proliferative inflammatory atrophy were noted only in patients with chronic inflammation. HGPIN was identified in 22 of the initial biopsy cases, specifically in 21 (10.3%) cases with inflammation and one case (2.4%) without inflammation. In follow-up biopsies, 70 patients (34.7%) with chronic inflammation were found to have prostatic adenocarcinoma with Gleason pattern 3 + 3 (42.9%; grade group 1), Gleason pattern 3 + 4(24.3%; grade group 2), Gleason pattern 4 + 3 (10%; grade group 3) and Gleason scores of 8 or higher (22.8%; grade groups 4 or 5), whereas cancer was found in 10 patients (23.8%) without chronic inflammation in the initial biopsy. Patients whose initial biopsies were benign and without inflammation did not show evidence of high-grade cancer (Gleason score of 8 or higher). Closely encroaching inflammation was observed more frequently in cancers of grade group 2 or above (76.5%, 13/17) compared with grade group 1 (50.0%, 3/6). Conclusions Our findings provide additional data supporting a role for chronic inflammation in the development of prostatic adenocarcinoma.
{"title":"The Role of Chronic Inflammation in Prostate Carcinogenesis: A Follow-Up Study","authors":"Wei Chen, Liwei Jia, Sanjay Gupta, G. MacLennan","doi":"10.32948/AUO.2019.01.14","DOIUrl":"https://doi.org/10.32948/AUO.2019.01.14","url":null,"abstract":"Purpose To investigate the role of chronic inflammation in prostatic carcinogenesis with an emphasis on cancers of grade group 2 or above. Methods The presence/absence and extent of chronic inflammation and other relevant pathological findings were assessed using prostate needle biopsies obtained from patients with clinical parameters with suspicion of malignancy. In patients with no prior prostate cancer, follow-up biopsies were reviewed and correlated with the initial pathological findings. Results Of 1,006 prostate needle biopsy cases accessioned over 3 years at our institution, the initial biopsies of 244 cases were identified with no evidence of prostate cancer. These cases were divided into two subsets, including 202 cases with and 42 without chronic inflammation. Pathological findings assessed in this subset included post-atrophic hyperplasia, proliferative inflammatory atrophy, and high-grade prostatic intraepithelial neoplasia (HGPIN). Post-atrophic hyperplasia and proliferative inflammatory atrophy were noted only in patients with chronic inflammation. HGPIN was identified in 22 of the initial biopsy cases, specifically in 21 (10.3%) cases with inflammation and one case (2.4%) without inflammation. In follow-up biopsies, 70 patients (34.7%) with chronic inflammation were found to have prostatic adenocarcinoma with Gleason pattern 3 + 3 (42.9%; grade group 1), Gleason pattern 3 + 4(24.3%; grade group 2), Gleason pattern 4 + 3 (10%; grade group 3) and Gleason scores of 8 or higher (22.8%; grade groups 4 or 5), whereas cancer was found in 10 patients (23.8%) without chronic inflammation in the initial biopsy. Patients whose initial biopsies were benign and without inflammation did not show evidence of high-grade cancer (Gleason score of 8 or higher). Closely encroaching inflammation was observed more frequently in cancers of grade group 2 or above (76.5%, 13/17) compared with grade group 1 (50.0%, 3/6). Conclusions Our findings provide additional data supporting a role for chronic inflammation in the development of prostatic adenocarcinoma.","PeriodicalId":33190,"journal":{"name":"Annals of Urologic Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69471460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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