Correlation of Ki-67 and p53 With the New World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia

2001 ◽  
Vol 125 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Stephen J. Cina ◽  
Kristen J. Lancaster-Weiss ◽  
Kristen Lecksell ◽  
Jonathan I. Epstein
Keyword(s):  
Papillary Carcinoma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Papillary Lesions ◽  
Flat Lesions ◽  
Papillary Hyperplasia ◽  
Health Organization ◽  
Papillary Neoplasm

Abstract Objective.—The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. Design.—We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. Results.—In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. Conclusions.—An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a “field effect” with occult molecular aberration.

scholarly journals Expression of Ki-67 in Low-Grade and High-Grade Astrocytomas

2018 ◽  
Vol 27 (3) ◽  
pp. 225-230
Author(s):  
Cléciton Braga Tavares ◽  
Francisca Das Chagas Sheyla Almeida Gomes Braga ◽  
Emerson Brandão Sousa ◽  
José Nazareno Pearce de Oliveira Brito
Keyword(s):  
Survival Time ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Exclusion Criteria ◽  
World Health Organization Classification ◽  
Ki 67 ◽  
Mesh Terms ◽  
Health Organization ◽  
Selection Of

Objective. This review aims to carry out a survey on the importance of Ki67 in the astrocytomas study. Methods. A search in the electronic database of Medline via PubMed and using MESH terms was carried out. Articles were published between January 2005 and December 2015. All studies were analyzed by two experienced researchers, using inclusion and exclusion criteria for the selection of studies. Results. Five studies showed an association between cell proliferation and survival time. Four articles mentioned as cut-off point for survival a Ki67 of 10% and a fifth article a Ki67 of 14.3. A study showed an association between therapeutic failure and Ki67. Four studies have made the association between Ki67 and World Health Organization classification. Conclusion. High levels of Ki67 are associated to high grade astrocytomas and lower survival time.

scholarly journals Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors

2018 ◽  
Vol 6 (4) ◽  
pp. 85 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi
Keyword(s):  
Brain Tumors ◽  
Clonal Evolution ◽  
Pediatric Brain Tumors ◽  
Genetic Alterations ◽  
World Health ◽  
Driver Mutations ◽  
Low Grade ◽  
High Grade ◽  
Genetic Profiling ◽  
Health Organization

Brain tumors are highly heterogeneous and have been classified by the World Health Organization in various histological and molecular subtypes. Gliomas have been classified as ranging from low-grade astrocytomas and oligodendrogliomas to high-grade astrocytomas or glioblastomas. These tumors are characterized by a peculiar pattern of genetic alterations. Pediatric high-grade gliomas are histologically indistinguishable from adult glioblastomas, but they are considered distinct from adult glioblastomas because they possess a different spectrum of driver mutations (genes encoding histones H3.3 and H3.1). Medulloblastomas, the most frequent pediatric brain tumors, are considered to be of embryonic derivation and are currently subdivided into distinct subgroups depending on histological features and genetic profiling. There is emerging evidence that brain tumors are maintained by a special neural or glial stem cell-like population that self-renews and gives rise to differentiated progeny. In many instances, the prognosis of the majority of brain tumors remains negative and there is hope that the new acquisition of information on the molecular and cellular bases of these tumors will be translated in the development of new, more active treatments.

Low-Grade Papillary Urothelial Carcinoma of the Urinary Bladder: A Clinicopathologic Analysis of a Post–World Health Organization/International Society of Urological Pathology Classification Cohort From a Single Academic Center

2010 ◽  
Vol 134 (8) ◽  
pp. 1160-1163
Author(s):  
Hiroshi Miyamoto ◽  
Fadi Brimo ◽  
Luciana Schultz ◽  
Huihui Ye ◽  
Jeremy S. Miller ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
World Health Organization ◽  
International Society ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
The Mean ◽  
Papillary Urothelial Carcinoma ◽  
Health Organization ◽  
Grade Progression

Abstract Context.—Few large cohort studies have addressed outcome in patients with noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following implementation of the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification. Objective.—To evaluate our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess outcome and interobserver agreement. Design.—Files were searched for all patients diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for accuracy of classification. Results.—A total of 112 cases initially diagnosed as LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by nonurologic pathologists were reclassified as high-grade papillary urothelial carcinoma and were excluded. The mean length of follow-up was 40.1 months (range, 2–113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%), including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high-grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade progression, 7 (37%) also developed stage progression (invasive carcinoma, n  =  5; metastatic carcinoma, n  =  2). Seven patients eventually underwent radical cystectomy. None of the 104 patients died of bladder cancer. The mean number of recurrence episodes was 3.11. The mean durations of time to first recurrence and time to grade progression were 13.9 months and 25.1 months, respectively. The mean size of initial tumors was 1.73 cm. There was no significant correlation between tumor size, patient age, sex, or smoking history and the likelihood for recurrence or grade progression. A significantly higher rate of recurrence was seen in patients with multiple tumors at initial diagnosis (P  =  .04). Conclusions.—A tendency to underdiagnose high-grade papillary urothelial carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa developed recurrence, with an 18.3% incidence of grade progression and a 6.7% incidence of stage progression. Patients with multiple initial tumors had significantly higher risk of developing recurrence.

scholarly journals Clinicopathological Significance of Nestin Expression as a Diagnostic and Prognostic Marker in Brain Gliomas, Independent of IDH Mutation

2021 ◽  
Author(s):  
Chang Gok Woo
Keyword(s):  
Poor Prognosis ◽  
Tissue Microarrays ◽  
Adult Brain ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Nestin Expression ◽  
High Grade Gliomas ◽  
Health Organization ◽  
Brain Gliomas

Abstract Background: Nestin, a type VI intermediate filament, is expressed in neuroepithelial cells during embryogenesis and has been expressed in various human tumors. Recent studies have reported that expression is associated with poor prognosis in brain tumors, but the results are inconclusive. In this study, we evaluated usefulness of Nestin expression using immunohistochemistry as a diagnostic and prognostic biomarker for IDH mutation and the new World Health Organization (WHO) classification.Methods: To investigate Nestin expression, immunohistochemistry was performed on 92 adult brain gliomas using tissue microarrays. We further analyzed the clinical characteristics and survival outcomes according to Nestin expression and examined its correlation with another glioma biomarker, IDH mutation.Results: Sixty patients (65.2%) were Nestin-positive (weak and strong). Nestin expression and intensity were significantly correlated with age, location, diagnosis, and IDH mutations. Old age and high-grade gliomas showed a higher frequency and stronger intensity of Nestin expression than those of young age and with low-grade gliomas (p<0.001). Gliomas with IDH mutations that are located in the frontal lobe showed no expression or had weak positivity. Multivariate analysis demonstrated that Nestin expression (weak, hazard ratio [HR] 5.39, p=0.036; strong, HR 8.43, p=0.007) and IDH wildtype (HR 7.63; p=.001) were significant independent prognostic factors. Moreover, patients with tumors expressing Nestin showed shorter survival (p<0.001).Conclusions: Nestin expression exhibits high intensity in high-grade gliomas and is a useful diagnostic marker. High expression and level of Nestin were significantly correlated with worse survival and was considered a significant marker of poor prognosis in new WHO classification, independent of IDH mutation.

Survivin as a Useful Adjunct Marker for the Grading of Papillary Urothelial Carcinoma

2008 ◽  
Vol 132 (2) ◽  
pp. 224-231
Author(s):  
Ying-bei Chen ◽  
Jiangling J. Tu ◽  
Jean Kao ◽  
Xi K. Zhou ◽  
Yao-Tseng Chen
Keyword(s):  
Urothelial Carcinoma ◽  
Messenger Rna ◽  
Interobserver Variability ◽  
World Health ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Grade Group ◽  
Ki 67 ◽  
Papillary Urothelial Carcinoma

Abstract Context.—Distinguishing low-grade and high-grade noninvasive papillary urothelial carcinoma based on morphologic criteria can be challenging and adjunct markers are highly desirable. Survivin, presumably an antiapoptotic protein, was previously proposed as a prognostic marker for urothelial carcinoma. Objective.—To assess interobserver variability by 2004 World Health Organization classification and the value of survivin and Ki-67 as potential markers for grading noninvasive papillary urothelial carcinoma. Design.—Fifty-one bladder biopsies were graded blindly by 5 experienced general surgical pathologists. The protein and messenger RNA expression of survivin and Ki-67 was evaluated by immunohistochemistry and quantitative reverse transcription–polymerase chain reaction using paraffin-embedded tissue. The immunohistochemistry result was quantitatively analyzed using a computer-based color deconvolution module. Results.—The diagnostic agreement among 5 pathologists was fair to poor, with 32% of the cases graded differently by at least 2 raters. All cases were divided into 3 groups: consensus low-grade, consensus high-grade, and indeterminate. The percentage of urothelial cells with positive survivin nuclear staining (survivin score) was significantly higher in the high-grade than in the low-grade group (P &lt; .001). Survivin score outperformed Ki-67 in separating the high-grade group from the low-grade group and showed a significantly higher predictive accuracy for high-grade recurrence than the histologic grade. The disagreement of grading for the indeterminate group could be resolved by their survivin scores in most cases. Survivin messenger RNA level correlated well with survivin score by immunohistochemistry but was not a more discriminating marker. Conclusions—Significant interobserver variability exists in grading low-grade versus high-grade papillary urothelial carcinoma. Survivin immunohistochemical staining can be a useful adjunct tool for the grading of challenging cases.

scholarly journals Survival and low-grade glioma: the emergence of genetic information

2015 ◽  
Vol 38 (1) ◽  
pp. E6 ◽  
Author(s):  
Elizabeth B. Claus ◽  
Kyle M. Walsh ◽  
John K. Wiencke ◽  
Annette M. Molinaro ◽  
Joseph L. Wiemels ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Young Patients ◽  
High Grade Glioma ◽  
The United States ◽  
Low Grade Glioma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Who Grade ◽  
Health Organization

Significant gaps exist in our understanding of the causes and clinical management of glioma. One of the biggest gaps is how best to manage low-grade (World Health Organization [WHO] Grade II) glioma. Low-grade glioma (LGG) is a uniformly fatal disease of young adults (mean age 41 years), with survival averaging approximately 7 years. Although LGG patients have better survival than patients with high-grade (WHO Grade III or IV) glioma, all LGGs eventually progress to high-grade glioma and death. Data from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute suggest that for the majority of LGG patients, overall survival has not significantly improved over the past 3 decades, highlighting the need for intensified study of this tumor. Recently published research suggests that historically used clinical variables are not sufficient (and are likely inferior) prognostic and predictive indicators relative to information provided by recently discovered tumor markers (e.g., 1p/19q deletion and IDH1 or IDH2 mutation status), tumor expression profiles (e.g., the proneural profile) and/or constitutive genotype (e.g., rs55705857 on 8q24.21). Discovery of such tumor and constitutive variation may identify variables needed to improve randomization in clinical trials as well as identify patients more sensitive to current treatments and targets for improved treatment in the future. This article reports on survival trends for patients diagnosed with LGG within the United States from 1973 through 2011 and reviews the emerging role of tumor and constitutive genetics in refining risk stratification, defining targeted therapy, and improving survival for this group of relatively young patients.

Rare ovarian tumors: an update on diagnosis and treatment

2020 ◽  
Vol 30 (6) ◽  
pp. 879-887 ◽  
Author(s):  
Charlotte Debuquoy ◽  
Clemence Romeo ◽  
Helene Vanacker ◽  
Isabelle Ray-Coquard
Keyword(s):  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Tumor Subtypes ◽  
Ovarian Cancers ◽  
Gynecology And Obstetrics ◽  
The Family ◽  
Rhabdoid Tumors ◽  
Health Organization ◽  
Tumor Types

Rare ovarian cancers occur frequently. Almost half of ovarian malignancies relate to several different ‘rare’ histotypes, according to the World Health Organization. The most common tumors are epithelial tumors, including high grade serous carcinomas, the presumed ‘frequent ovarian cancers’, together with low grade serous, mucinous, endometrioid, clear cell, and carcinosarcomas. Sex cord stromal tumors and germ cell carcinomas define two other groups of different subtypes, and small cell carcinomas are an independent high grade subtype closely related to the family of rhabdoid tumors. All of these cancers are primary ovarian cancers, classified by the International Federation of Gynecology and Obstetrics. However, the tumor subtypes display various epidemiologic, clinical, pathological, prognostic, and therapeutic characteristics. Because of the scarcity of data, current understanding of each subtype is limited and treatment has generally been derived from the more common tumor types. The aim of this article is to review the current literature on rare ovarian malignancies.

Volumetric Assessment of Glioma Removal by Intraoperative High-field Magnetic Resonance Imaging

Neurosurgery ◽  
2004 ◽  
Vol 55 (2) ◽  
pp. 358-371 ◽  
Author(s):  
Christopher Nimsky ◽  
Atsushi Fujita ◽  
Oliver Ganslandt ◽  
Boris von Keller ◽  
Rudolf Fahlbusch
Keyword(s):  
Magnetic Resonance ◽  
High Field ◽  
Tumor Volume ◽  
Tumor Resection ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Resonance Imaging ◽  
Glioma Surgery ◽  
Health Organization

Abstract OBJECTIVE: To investigate the contribution of high-field intraoperative magnetic resonance imaging (iMRI) for further reduction of tumor volume in glioma surgery. METHODS: From April 2002 to June 2003, 182 neurosurgical procedures were performed with a 1.5-T magnetic resonance system. Among patients who underwent these procedures, 47 patients with gliomas (14 with World Health Organization Grade I or II glioma, and 33 with World Health Organization Grade III or IV glioma) who underwent craniotomy were investigated retrospectively. Completeness of tumor resection and volumetric analysis were assessed with intraoperative imaging data. RESULTS: Surgical procedures were influenced by iMRI in 36.2% of operations, and surgery was continued to remove residual tumor. Additional further resection significantly reduced the percentage of final tumor volume compared with first iMRI scan (6.9% ± 10.3% versus 21.4% ± 13.8%; P &lt; 0.001). Percentages of final tumor volume also were significantly reduced in both low-grade (10.3% ± 11.5% versus 25.8% ± 16.3%; P &lt; 0.05) and high-grade gliomas (5.4% ± 9.9% versus 19.5% ± 13.0%; P &lt; 0.001). Complete resection was achieved finally in 36.2% of all patients (low-grade, 57.1%; high-grade, 27.3%). Among the 17 patients in whom complete tumor resection was achieved, 7 complete resections (41.2%) were attributable to further tumor removal after iMRI. We did not encounter unexpected events attributable to high-field iMRI, and standard neurosurgical equipment could be used safely. CONCLUSION: Despite extended resections, introduction of high-field iMRI in conjunction with functional navigation did not translate into an increased risk of postoperative deficits. The use of high-field iMRI increased radicality in glioma surgery without additional morbidity.

scholarly journals What Is New on Ovarian Carcinoma: Integrated Morphologic and Molecular Analysis Following the New 2020 World Health Organization Classification of Female Genital Tumors

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 697
Author(s):  
Antonio De Leo ◽  
Donatella Santini ◽  
Claudio Ceccarelli ◽  
Giacomo Santandrea ◽  
Andrea Palicelli ◽  
...  
Keyword(s):  
Clear Cell ◽  
World Health ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Histologic Subtype ◽  
Health Organization ◽  
Female Genital

Ovarian carcinomas represent a heterogeneous group of neoplasms consisting of separate entities with distinct risk factors, precursor lesions, pathogenesis, patterns of spread, molecular profiles, clinical course, response to chemotherapy, and outcomes. The histologic subtype and the related molecular features are essential for individualized clinical decision-making. The fifth edition of the World Health Organization classification of tumors of the female genital tract divides ovarian carcinomas into at least five main and distinct types of ovarian carcinomas: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, clear cell carcinoma, and mucinous carcinoma. Molecular pathology has improved the knowledge of genomic landscape of ovarian carcinomas identifying peculiar alterations for every histologic subtype. It is well-known that high-grade and low-grade serous carcinomas are separate entities with entirely different morphologic and molecular characteristics. TP53 and BRCA mutations are typical of high-grade serous carcinoma, whereas BRAF and KRAS mutations frequently occur in low-grade serous carcinoma. Endometrioid and clear cell carcinomas are frequently associated with endometriosis. Endometrioid tumors are characterized by β-catenin alterations, microsatellite instability, and PTEN and POLE mutations, while ARID1A mutations occur in both endometrioid and clear cell carcinomas. Mucinous carcinomas are uncommon tumors associated with copy-number loss of CDKN2A and KRAS alterations and metastasis from other sites should always be considered in the differential diagnosis.

scholarly journals Comparison between 1973 and 2004/2016 World Health Organization grading in upper tract urothelial carcinoma treated with radical nephroureterectomy

2021 ◽  
Author(s):  
Claudia Collà Ruvolo ◽  
Christoph Würnschimmel ◽  
Mike Wenzel ◽  
Luigi Nocera ◽  
Giuseppe Celentano ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
World Health Organization ◽  
The Other ◽  
Upper Tract Urothelial Carcinoma ◽  
World Health ◽  
Grading System ◽  
Low Grade ◽  
High Grade ◽  
Radical Nephroureterectomy ◽  
Health Organization

Abstract Aims The European Association of Urology guideline for upper tract urothelial carcinoma (UTUC) relies on two grading system: 1973 World Health Organization (WHO) and 2004/2016 WHO. No consensus has been made which classification should supersede the other and both are recommended in clinical practice. We hypothesized that one may be superior to the other. Methods Newly diagnosed non-metastatic UTUC patients treated with radical nephroureterectomy were abstracted from the Surveillance, Epidemiology, and End Results database (2010–2016). Kaplan–Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G1 vs. G2 vs. G3) or to 2004/2016 WHO (low-grade vs. high-grade) grading systems. Haegerty’s C-index quantified accuracy. Results Of 4271 patients, according to 1973 WHO grading system, 134 (3.1%) were G1, 436 (10.2%) were G2 and 3701 (86.7%) were G3; while according to 2004/2016 WHO grading system, 508 (11.9%) were low grade vs 3763 (88.1%) high grade. In multivariable CRMs, high grade predicted higher CSM (Hazard ratio: 1.70, p < 0.001). Conversely, neither G2 (p = 0.8) nor G3 (p = 0.1) were independent predictors of worse survival. The multivariable models without consideration of either grading system were 74% accurate in predicting 5-year CSM. Accuracy increased to 76% after either addition of the 1973 WHO or 2004/2016 WHO grade. Conclusions From a statistical standpoint, either 1973 WHO or 2004/2016 WHO grading system improves the accuracy of CSM prediction to the same extent. In consequence, other considerations such as intra- and interobserver variability may represent additional metrics to consider in deciding which grading system is better.

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