Genotyping of high-risk human papillomaviruses in p16/Ki-67-positive urothelial carcinoma cells: even a worm will turn

Cytopathology ◽  
2014 ◽  
Vol 26 (2) ◽  
pp. 106-113 ◽  
Author(s):  
A.-S. Advenier ◽  
J.-S. Casalegno ◽  
Y. Mekki ◽  
M. Decaussin-Petrucci ◽  
F. Mège-Lechevallier ◽  
...  
Rare Tumors ◽  
2011 ◽  
Vol 3 (4) ◽  
pp. 132-134 ◽  
Author(s):  
Tadashi Terada

The nested variant of urothelial carcinoma (NVUC) is characterized by the presence of benign-appearing urothelial carcinoma cells in the lamina propria, sparing the surface urothelial involvement. NVUC shows aggressive clinical course despite of benign-looking histology. Herein reported are two cases of NVUC. One is 80-year-old woman, and another is 78-year-old man. In both cases, atypical cells forming nests and tubules were seen in the lamina propria without surface urothelial involvement. One case resembled nephrogenic metaplasia and another proliferated Brunn's nest or inverted papilloma. Immunohistochemically, both cases showed positive p53 and high Ki67 labeling, suggesting that both cases are malignant. Immunohistochemically, one case was characterized by positive cytokeratins, EMA, p53, Ki-67 (labeling=15%), α-methylacyl CoA racemase, CA19-9, and MUC1, and another case by positive cytokeratins, EMA, p63, p53, Ki-67 (lebeling=30%), CD10, CEA, and MUC1. Cyto keratin immunoprofiles were described and other antigens’ expressions were shown. The patients are now free of tumor 6 and 15 months after the resection of the bladder tumor.


2013 ◽  
Vol 63 (6) ◽  
pp. 311-317 ◽  
Author(s):  
Masayo Shuto ◽  
Kenji Warigaya ◽  
Hiroshi Watanabe ◽  
Michio Shimizu ◽  
Toshio Fukuda ◽  
...  

2016 ◽  
Vol 10 (3) ◽  
pp. 267-270
Author(s):  
Tadashi Terada

Recently the author encountered a peculiar tumour of the bladder consisting of the following three components: MALT lymphoma, scattered poorly cohesive sarcomatoid urothelial carcinoma within MALT lymphoma, and surface non-invasive, low-grade conventional urothelial carcinoma (UC) occurring in a 65-year-old female. A low-power view showed MALT. Meticulous observations revealed a small amount of non-invasive, low-grade conventional UC at the surface area. In addition, meticulous observations identified a small number of cytokeratin-positive, poorly cohesive sarcomatoid UC cells scattered within the MALT lymphoma. The MALT lymphoma was typical. Immunohistochemically, the scattered sarcomatoid cells within the MALT lymphoma were positive for various types of CK, EMA, p53 and Ki-67 (LI = 70%). The MALT lymphoma was composed mainly of B-cells (CD10, CD20, CD23, CD79α, κ-chains and λ-chain), but T-cells positive for CD3, CD4, CD5, CD43 or CD45RO were seen in a very small number. This scattering sarcomatoid UC within MALT lymphoma of bladder has not been reported.


Author(s):  
Karim Nagi ◽  
Ishita Gupta ◽  
Hamda A Al-Thawadi ◽  
Ayesha Jabeen ◽  
Mohammed I. Malk ◽  
...  

Background: Several studies have shown the presence of onco viral DNA in colorectal tumor tissues. Viral infection by onco-viruses such as Human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) are well-known to be involved in the onset and/or progression of numerous human carcinomas. Methods: We explored the co-presence of high-risk HPVs and EBV in a cohort of colorectal cancer samples from Lebanon (94) and Syria (102) by PCR, immunohistochemistry and tissue microarray. Results: The results of the study point out that 54% of colorectal cancer cases in Syria are positive for high-risk HPVs, while 30% of the cases in Lebanon are positive for these viruses; the most frequent high-risk HPV types in these populations are 16, 18, 31, 33 and 35. Analysis of LMP1 showed similar results in both populations; 36% of Syrian and 31% of Lebanese samples. Additionally, we report that EBV and high-risk HPVs are co-present in these samples. In Syrian samples, EBV and HPVs are co-present in 16% of the population, however, in the Lebanese samples, 20% of the cases are positive for both EBV and HPVs; their co-presence is associated with high/intermediate grade invasive carcinomas. Conclusion: These data suggest that EBV and high-risk HPVs are co-present in human colorectal cancers where they can cooperate in the progression of these cancers. Nevertheless, further studies are needed to elucidate the role of those oncoviruses in the development of human colorectal carcinomas.


Author(s):  
Shicong Lai ◽  
Xingbo Long ◽  
Pengjie Wu ◽  
Jianyong Liu ◽  
Samuel Seery ◽  
...  

Abstract Objective To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. Methods This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. Results With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas’ model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients’ net benefit. Conclusions This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.


2021 ◽  
Vol 79 ◽  
pp. S1105-S1106
Author(s):  
A. Martini ◽  
C. Lonati ◽  
A. Necchi ◽  
A. Briganti ◽  
F. Montorsi ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 714
Author(s):  
Matthias Läsche ◽  
Horst Urban ◽  
Julia Gallwas ◽  
Carsten Gründker

Cervical cancer is responsible for around 5% of all human cancers worldwide. It develops almost exclusively from an unsolved, persistent infection of the squamocolumnar transformation zone between the endo- and ecto-cervix with various high-risk (HR) human papillomaviruses (HPVs). The decisive turning point on the way to persistent HPV infection and malignant transformation is an immune system weakened by pathobionts and oxidative stress and an injury to the cervical mucosa, often caused by sexual activities. Through these injury and healing processes, HPV viruses, hijacking activated keratinocytes, move into the basal layers of the cervical epithelium and then continue their development towards the distal prickle cell layer (Stratum spinosum). The microbial microenvironment of the cervical tissue determines the tissue homeostasis and the integrity of the protective mucous layer through the maintenance of a healthy immune and metabolic signalling. Pathological microorganisms and the resulting dysbiosis disturb this signalling. Thus, pathological inflammatory reactions occur, which manifest the HPV infection. About 90% of all women contract an HPV infection in the course of their lives. In about 10% of cases, the virus persists and cervical intra-epithelial neoplasia (CIN) develops. Approximately 1% of women with a high-risk HPV infection incur a cervical carcinoma after 10 to 20 years. In this non-systematic review article, we summarise how the sexually and microbial mediated pathogenesis of the cervix proceeds through aberrant immune and metabolism signalling via CIN to cervical carcinoma. We show how both the virus and the cancer benefit from the same changes in the immune and metabolic environment.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dexin Shen ◽  
Yayun Fang ◽  
Fenfang Zhou ◽  
Zhao Deng ◽  
Kaiyu Qian ◽  
...  

Abstract Background CDCA3 is an important component of the E3 ligase complex with SKP1 and CUL1, which could regulate the progress of cell mitosis. CDCA3 has been widely identified as a proto-oncogene in multiple human cancers, however, its role in promoting human bladder urothelial carcinoma has not been fully elucidated. Methods Bioinformatic methods were used to analyze the expression level of CDCA3 in human bladder urothelial carcinoma tissues and the relationship between its expression level and key clinical characteristics. In vitro studies were performed to validate the specific functions of CDCA3 in regulating cell proliferation, cell migration and cell cycle process. Alterations of related proteins was investigated by western blot assays. In vivo studies were constructed to validate whether silencing CDCA3 could inhibit the proliferation rate in mice model. Results Bioinformatic analysis revealed that CDCA3 was significantly up-regulated in bladder urothelial carcinoma samples and was related to key clinical characteristics, such as tumor grade and metastasis. Moreover, patients who had higher expression level of CDCA3 tend to show a shorter life span. In vitro studies revealed that silencing CDCA3 could impair the migration ability of tumor cells via down-regulating EMT-related proteins such as MMP9 and Vimentin and inhibit tumor cell growth via arresting cells in the G1 cell cycle phase through regulating cell cycle related proteins like p21. In vivo study confirmed that silencing CDCA3 could inhibit the proliferation of bladder urothelial carcinoma cells. Conclusions CDCA3 is an important oncogene that could strengthen the migration ability of bladder urothelial carcinoma cells and accelerate tumor cell growth via regulating cell cycle progress and is a potential biomarker of bladder urothelial carcinoma.


BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e027066
Author(s):  
Marcus L Jamil ◽  
Mustafa Deebajah ◽  
Akshay Sood ◽  
Shaheen Alanee

IntroductionThe treatment standard for high-risk upper urinary tract urothelial carcinoma (UUTUC) is radical nephroureterectomy. However, some patients may be unfit or unwilling, and in such patients the available alternatives are suboptimal. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinom (UC). We designed the current study to determine the safety and efficacy of administering MK-3475 (a monoclonal antibody targeting interaction between PD-1 and its ligand) in combination with bacillus Calmette-Guerin (BCG) in high-risk non-muscle invasive UUTUC patients.MethodsThis represents a single-centre phase-II efficacy study of MK-3475 therapy in combination with BCG for subjects, 18 years of age or older, with pathologically documented non-muscle invasive high-risk UUTUC unfit or unwilling to be treated with radical nephroureterectomy. Twenty subjects will be enrolled; patients will receive treatment with 200 mg of MK-3475 every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety and efficacy of administering MK-3475 at a fixed dose of 200 mg every 3 weeks in conjunction with intrapelvic BCG. Secondary objectives include 19 week and the 3, 12 and 24-month post-treatment completion complete response and progression-free rate assessments.Ethics and disseminationThe study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference.Trial registration numberNCT03345134


2016 ◽  
Vol 60 (5) ◽  
pp. 445-450 ◽  
Author(s):  
Yiang Hui ◽  
Katrine Hansen ◽  
Jayasimha Murthy ◽  
Danielle Chau ◽  
C. James Sung ◽  
...  

Objective: A vast majority of cervicovaginal intraepithelial lesions are caused by high-risk human papillomaviruses (HPVs). The Pap test has been the sole method used for the screening of cervicovaginal squamous intraepithelial lesions (SIL). Recently, the FDA approved an HPV-DNA assay as a method of primary screening. We report on a series of FDA-approved HPV-DNA test-negative SIL with HPV genotyping, using an alternative method on the corresponding surgical biopsy specimens. Study Design: A retrospective review identified cytology-positive HPV-negative cases over a 15-month period at a tertiary care gynecologic oncology institution. Corresponding biopsies were reviewed and genotyped for high-risk HPVs. Results: Of the 18,200 total cases, 17 patients meeting the study criteria were selected with 27 surgical specimens corresponding to their cytologic diagnoses. Four patients with high-grade lesions were identified, 3 of whom (75%) were positive for HPV. One of these 4 patients (25%) showed high-grade SIL on biopsies from 4 separate sites in the cervix and vagina. Multiviral HPV infections were frequent. Conclusions: We discuss the relevance of cotesting for screening cervical SILs and emphasize that false-negative results are possible with the FDA-approved HPV screening assay, also in patients with high-grade SIL. These cases may be detectable by cytologic examination and this suggests that the Pap test remains an important diagnostic tool.


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