ErbB receptor tyrosine kinase family expression levels in urothelial bladder carcinoma

ErbB receptor tyrosine kinases family plays an important role in cell cycle regulation. Overexpression of ErbB receptors has been described in several solid tumors. The aim of this study was to investigate the levels of ErbB1, ErbB2, ErbB3, and ErbB4 expression in bladder cancer. Urinary bladder tumor samples were obtained from 33 bladder cancers and 7 non-cancerous bladder biopsies. The levels of ErbB1, ErbB2, ErbB3, and ErbB4 genes expression in bladder cancer were determined by real-time PCR. The presence of protein was confirmed by immunostaining. Expression of ErbB1, ErbB2, ErbB3, and ErbB4 genes increased 0.67, 4.72, 2.89, and 2.65-fold, respectively, in bladder tumors as compared with normal tissue. There was a significant difference between immunostaining results of ErbB4 protein in bladder tumors and normal bladder tissue (P < 0.01). The present data suggest that ErbB2, ErbB3, and ErbB4 genes may have a role in bladder cancer tumorigenesis.     

Proliferative and apoptotic markers in prostate carcinoma in relation to androgen receptor

Prostate carcinoma, one of the most frequent male malignancies, is in certain stages of its development significantly influenced by androgens. Therefore, we carried out a retrospective study on a set of 130 patients with nongeneralized, localized prostate carcinoma (stage T1-T2, PSA up to 25 ng/ml). We determined immunohistochemically the expression of proliferation markers PCNA and Ki67, Bax, p53, Bcl-2, p21waf1, p27kiP1 and compared them with the expression of the androgen receptor (AR). Multivariation statistical analysis of the results using the chi-square test with Pearson's correction and variability analysis using the SPSS 8.0 software program showed a strong correlation of the PCNA and Ki67 proliferation markers with the expression of hormonal dependence and apoptosis markers. The expression of PCNA correlated strongly with p27 kip1 and Bax, while the expression of Ki67 correlated most strongly with p27 kip1 and Bcl-2. The expression of p27 kip1 correlated with the expression of androgen receptor, PCNA, Ki67 as well as Bcl-2. None of the observed markers correlated significantly with Gleason's score. We did not find substantial significant relation between the observed markers and the expression of p53 and p21 waf1. The results indicate a significant role of the expression of p27 kip1 protein in regulating proliferative activity and hormonal responsiveness in the initial stage of prostate carcinoma.     

E-cadherin expression in invasive urothelial carcinoma

E-cadherin (E-CD) is a transmembrane glycoprotein involved in intercellular adhesion. A loss or reduction in E-CD expression has been linked to the invasive phenotype of a wide variety of human neoplasms, including bladder tumors. The objective of this study was to compare the E-CD expression at different depths of tumor invasion below the bladder's basement membrane in high- and low-grade urothelial carcinomas to investigate whether deeper tumor invasion and higher-grade invasive urothelial carcinomas are associated with decreased E-CD expression. E-cadherin staining was performed on 29 formalin-fixed, paraffin-embedded sections from high- and low-grade urothelial carcinoma specimens using an automatic immunohistochemical stainer. The sections were divided into three categories according to the depth of invasion below the basement membrane: upper, middle, and lower. The percentage and intensity of E-CD cell membrane staining for the three categories were calculated using a quantitative automated cellular imaging system. The percentage of cells that stained for E-CD was 82.6% +/- 1.4% (mean +/- SD) in the upper layer, 59.6% +/- 2.2% in the middle layer, and 29.4% +/- 2.7% in the lower layer. The intensity of E-CD expression was 64.7 +/- 3.2 units in the upper layer, 43.3 +/- 2.9 units in the middle layer, and 26.1 +/- 3.1 units in the lower layer. There were significant differences between the three layers in both the percentage and intensity of cellular E-CD staining (P<.05). Normal urothelium, high-grade urothelial dysplasia/carcinoma in situ, and superficial noninvasive papillary urothelial carcinoma maintained E-CD expression. However, once malignant cells infiltrated through the basement membrane, E-CD expression decreased. The more poorly differentiated urothelial carcinoma, the deeper the nests, and the smaller the clusters of neoplastic cells within the tumor were, and the more decrease in E-CD expression noted. The degree of decreased E-CD expression was directly proportional to the degree of tumor differentiation and depth of infiltration in invasive urothelial carcinoma. Down-regulation of E-CD may be one of the pathways responsible for tumor differentiation and may promote deeper invasion in urothelial carcinomas.     

Herpes simplex infection in urothelial carcinoma

Herpes simplex virus (HSV), a member of the Herpesviridae family, is a very common pathogen that can infect any site in the body. Urothelial carcinoma (UC) is a common malignancy of the urinary tract. The possibility of HSV infection in cases of UC has attracted little attention. In this study, we investigated the possible presence of HSV in UC and non-neoplastic urothelium. We examined the incidence of HSV infection in 100 samples of UC from 78 patients and 50 samples of non-neoplastic urothelium from 50 autopsy cases using immunohistochemical staining and amplification of DNA using polymerase chain reaction (PCR). Infection by HSV was detected in 39 of the 100 samples of UC (35 of 78 patients) using immunohistochemical staining and/or PCR analysis, in marked contrast with 1 of 50 samples of non-neoplastic urothelium. There was no significant relationship between infection by HSV and anatomical site, growth pattern or depth of invasion of UC, but the frequency of HSV infection was significantly higher in females than in males. Our findings indicate that UCs become infected with HSV much more easily than non-neoplastic urothelium.     

雄激素受体在乳腺癌中的表达及其与雌、孕激素受体和HER2的关系

目的 研究雄激素受体(AR)在乳腺浸润性导管癌中的表达及其与雌激素受体(ER)、孕激素受体(PR)和HER2状态的关系,探讨其作为乳腺癌治疗靶点的可行性.方法 采用免疫组织化学EnVision法检测AR、ER、PR、HER2在175例乳腺浸润性导管癌中的表达,依据结果分为腺腔A型、腺腔B型、HER2过表达型和三阴性型(ER-/PR-/HER2-)组.结果 175例中AR阳性88例(50.3%),AR表达与ER、PR、HER2均呈正相关(P＜0.01).腺腔A型53例(30.3%),腺腔B型33例(18.9%),HER2过表达型23例(13.1%),三阴性型66例(37.7%),AR阳性率分别为56.6%(30/53),75.8%(25/33)、47.8%(11/23)和33.3%(22/66),组间AR阳性率差异显著(x2=17.054,P=0.001).三阴性型组AR阳性者核分裂象较少(x2=5.140,P=0.023),腺腔A型组AR阳性者多为年轻患者(x2=4.567,P=0.033),差异有统计学意义.其他组内AR表达与否和临床病理学特征比较无统计学意义.结论 AR在乳腺癌中有较高的阳性率,可作为乳腺癌,特别是三阴性型乳腺癌的治疗靶点.     

雄激素受体在乳腺癌中的表达及其与雌、孕激素受体和HER2的关系

目的 研究雄激素受体(AR)在乳腺浸润性导管癌中的表达及其与雌激素受体(ER)、孕激素受体(PR)和HER2状态的关系,探讨其作为乳腺癌治疗靶点的可行性.方法 采用免疫组织化学EnVision法检测AR、ER、PR、HER2在175例乳腺浸润性导管癌中的表达,依据结果分为腺腔A型、腺腔B型、HER2过表达型和三阴性型(ER-/PR-/HER2-)组.结果 175例中AR阳性88例(50.3%),AR表达与ER、PR、HER2均呈正相关(P＜0.01).腺腔A型53例(30.3%),腺腔B型33例(18.9%),HER2过表达型23例(13.1%),三阴性型66例(37.7%),AR阳性率分别为56.6%(30/53),75.8%(25/33)、47.8%(11/23)和33.3%(22/66),组间AR阳性率差异显著(x2=17.054,P=0.001).三阴性型组AR阳性者核分裂象较少(x2=5.140,P=0.023),腺腔A型组AR阳性者多为年轻患者(x2=4.567,P=0.033),差异有统计学意义.其他组内AR表达与否和临床病理学特征比较无统计学意义.结论 AR在乳腺癌中有较高的阳性率,可作为乳腺癌,特别是三阴性型乳腺癌的治疗靶点.     

Polyomavirus infection and urothelial carcinoma

Introduction: Polyomavirus infections are common in the general (adult) population with a reported prevalence of more than 80%. Polyomavirus can infect urothelial carcinoma and change the morphology of these malignant cells, as is shown in this paper. Material and Methods: An eighty year old Hispanic male was referred to the urology clinic for diagnosis and treatment. The submitted voided urine sample was concentrated, processed, and a SurePath preparation was made. Results and Discussion: The Papanicolaou‐stained slides contained single cells with very large hyperchromatic nuclei with a glassy appearance in addition to atypical neoplastic cells. The single cells with enlarged nuclei proved to stain positive for Simian virus 40 (SV40) antigen. The nuclei of these cells were 2 to 4 times larger than that of the surrounding noninfected atypical cells. These findings were confirmed on histologic sections prepared from tissue biopsy. Conclusion: In conclusion we report that it is difficult to distinguish benign polyomavirus infected cells from their malignant counterparts in cytology but not in histology. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

Nested variant of urothelial carcinoma

Nested variant of urothelial carcinoma is a rare neoplasm that is histologically characterized by large numbers of small, closely packed, haphazardly arranged, poorly defined, confluent irregular nests of bland-appearing urothelial cells infiltrating the lamina propria and the muscularis propria. Due to the cells' deceptively bland appearance, the tumors are sometimes misdiagnosed as benign lesions, leading in some cases to a significant delay in establishing the correct diagnosis and thus contributing to this neoplasm's advanced stage. Nested variant of urothelial carcinoma must be differentiated from the benign proliferative lesions of urothelium, such as von Brunn nests, cystitis cystica, cystitis glandularis, nephrogenic adenoma, inverted papilloma, and paraganglioma.     

不同ER、PR状态乳腺癌中AR的表达及其意义

目的探讨AR在不同ER、PR状态乳腺癌中的表达及意义。方法采用免疫组化方法检测AR、ER、PR在173例乳腺癌中的表达,依据结果分组:(1)AR状态分组:AR阳性组和AR阴性组;(2)ER、PR状态分组:En组(ER、PR均阴性)、Ep组[ER和(或)PR阳性];(3)AR、ER、PR联合分组:En-AR+(En组且AR阳性)、En-AR-(En组且AR阴性)、Ep-AR+(Ep组且AR阳性)、Ep-AR-(Ep组且AR阴性),其中En-AR-又称为均阴性组,其他三组统称为部分或完全阳性组。不同分组方法比较与临床病理特征的关系。结果Ep组AR阳性率62.8%(54/86),En组AR阳性率37.9%(33/87),两组差异有显著性(P=0.001),AR阳性组体积小、核分裂少、组织学分级低(P0.05);En-AR-组表现为核分裂多、组织学分级高(P0.01),此外En组内AR阳性者核分裂少、组织学分级低(P0.05),Ep组内AR阳性者临床分期高(P=0.000),En-AR+、Ep-AR+、Ep-AR-比较均无差异。结论AR在不同激素状态乳腺癌中表达的意义不同,ER、PR均阴性乳腺癌表达AR者预后较好,ER、PR阳性乳腺癌表达AR者临床分期高。在选择针对性药物时应考虑到不同激素受体状态的组合。     

Racial differences in the androgen/androgen receptor pathway in prostate cancer

Pathologic and epidemiologic data suggest that while little racial variation exists in prostate cancer prevalence ("autopsy cancer"), striking racial variation exists for the clinically diagnosed form of the disease. A review of the available literature was performed to define whether racial differences in serum androgen levels or qualitative or quantitative differences in the androgen receptor were correlated with prostate cancer incidence or severity. Black men were found to be exposed to higher circulating testosterone levels from birth to about age 35 years. Such differences were not consistently noted among older men. Significant differences also were found for dihydrotestosterone metabolites among black, white, and Asian men. Unique racial genetic polymorphisms were noted for the gene for 5 alpha-reductase type 2 among black and Asian men. Novel androgen receptor mutations recently have been described among Japanese, but not white, men with latent prostate cancer. Finally, androgen receptor gene polymorphisms leading to shorter or longer glutamine and glycine residues in the receptor protein are correlated with racial variation in the incidence and severity of prostate cancer. This same polymorphism also could explain racial variation in serum prostate-specific antigen levels. Collectively, these data strongly suggest racial differences within the androgen/androgen receptor pathway not only exist but could be one cause of clinically observed differences in the biology of prostate cancer among racial groups.     

Micropapillary urothelial carcinoma: Clinico-pathologic review

Micropapillary carcinoma is a rare distinct variant of high grade urothelial carcinoma, which has specific morphological characteristics and is almost always associated with muscularis propria and vascular invasion. No currently defined imaging techniques can reliably diagnose some types of deeply invasive urothelial carcinoma of urinary bladder, in particular its micropapillary variant. Therefore, the pathological findings are crucial in making the diagnosis. Micropapillary carcinoma (MPC) is a tumor with an aggressive clinical course, an advanced stage of disease at the time of presentation, and usually a poor outcome. Metastatic micropapillary carcinoma to bladder should always be included in the differential diagnosis. Correct histological diagnosis of this aggressive neoplasm would allow timely, albeit intense, radical treatment of the disease. The current most generally favored treatment option for all patients who present with MPC is immediate radical cystectomy.     

Micropapillary urothelial carcinoma of the ureter

Micropapillary urothelial carcinoma (MPUC) is a rare aggressive variant of urothelial carcinoma, associated with advanced tumor stage, high tendency to invade lymphovascular spaces, and metastasize to lymph nodes and other organs. Therefore, it has a poor prognosis. One of the most prominent histological features is the presence of small, round empty spaces surrounding infiltrating tumor nests. If detected, even a small focus of micropapillary pattern may be therapeutically significant; the higher proportion of micropapillary component, the worse the prognosis. Radical nephroureterectomy is the treatment of choice even in the setting of superficially invasive disease. Although, MPUC has been well studied in urinary bladder, only a few cases of MPUC in upper urinary tract have been described. We are describing a case of a 79-year old woman with micropapillary urothelial carcinoma involving ureter and review the literature of this rare entity.     

The androgen receptor gene mutations database: 2012 update

The current version of the androgen receptor gene (AR) mutations database is described. A major change to the database is that the nomenclature and numbering scheme now conforms to all Human Genome Variation Society norms. The total number of reported mutations has risen from 605 to 1,029 since 2004. The database now contains a number of mutations that are associated with prostate cancer (CaP) treatment regimens, while the number of AR mutations found in CaP tissues has more than doubled from 76 to 159. In addition, in a number of androgen insensitivity syndrome (AIS) and CaP cases, multiple mutations have been found within the same tissue samples. For the first time, we report on a disconnect within the AIS phenotype-genotype relationship among our own patient database, in that over 40% of our patients with a classic complete AIS or partial AIS phenotypes did not appear to have a mutation in their AR gene. The implications of this phenomenon on future locus-specific mutation database (LSDB) development are discussed, together with the concept that mutations can be associated with both loss- and gain-of-function, and the effect of multiple AR mutations within individuals. The database is available on the internet (http://androgendb.mcgill.ca), and a web-based LSDB with the variants using the Leiden Open Variation Database platform is available at http://www.lovd.nl/AR.     

Urine cytomorphology of micropapillary urothelial carcinoma

Micropapillary urothelial carcinoma (MPUC) is a rare subtype of urothelial carcinoma (UC) with an aggressive clinical course. The cytomorphologic features of MPUC in urine cytology have not been well described. In this study, 23 urine specimens (11 voided urines and 12 bladder washings) from 23 patients with MPUC on follow‐up surgical material and 28 specimens (14voided urines and 14 bladder washings) from 28 patients with high‐grade UCs (HGUC) were retrieved. Cytologic features (nuclear grade, cytoplasmic characteristics), architectural features (single cell pattern, true papillary structures, flat sheets/nests, three dimensional clusters, micropapillary (inside‐out, acinar‐like, or cauliflower with nuclei located peripherally)), and necrosis were evaluated. Clinical follow‐up was obtained by chart review. Two findings, micropapillae and cytoplasmic vacuoles, were seen more frequently in MPUC compared to HGUC, 81.0% vs. 14.3%, and 57.1% vs. 14.3%, respectively. The combination of these two findings had a sensitivity of 78%, a specificity of 86%, a positive predictive value of 82%, and a negative predictive value of 83% for the diagnosis of MPUC on subsequent biopsy. MPUC and HGUC can both exhibit a single cell pattern, papillary structures, flat sheets/nests, three dimensional clusters, high‐nuclear grade, and necrosis, thus these findings are not useful in distinguishing these entities. Chart review revealed that patients with MPUC had a higher rate of metastasis to lymph nodes and distant organs than HGUC, 57% vs. 4%. Therefore, the findings of cytoplasmic vacuoles and micropapillary structures in UC from a urine cytology specimen are associated with MPUC on subsequent biopsy. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.