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The Journal of Urology Nov 2016Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no... (Review)
Review
PURPOSE
Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms tumor to quantify the prognostic implications of the presence of individual tumor markers.
MATERIALS AND METHODS
We searched for English language studies from 1980 to 2015 performed in patients younger than 18 years with Wilms tumor and prognostic data. The protocol was conducted per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level II or III studies.
RESULTS
A total of 40 studies were included examining 32 biomarkers in 7,381 patients with Wilms tumor. Studies had a median of 61 patients, 24 biomarker positive patients per series and a median followup of 68.4 months. Median percentages of patients with stages 1, 2, 3, 4 and 5 tumors were 28.5%, 26.4%, 24.5%, 14.1% and 1.7%, respectively, and 10.2% had anaplasia. The strongest negative prognostic association was loss of heterozygosity at 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity at 1p and gain of function at 1q were also strongly linked to increased recurrence (2.93 and 2.86, respectively).
CONCLUSIONS
Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in patients with Wilms tumor. These data suggest targets for development of diagnostic tests and potential therapies.
Topics: Biomarkers, Tumor; Child; Humans; Kidney Neoplasms; Prognosis; Wilms Tumor
PubMed: 27259655
DOI: 10.1016/j.juro.2016.05.100 -
Indian Journal of Pathology &... 2022Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Anaplasia is a rare phenomenon seen in childhood RMS. The most common histologic subtype was...
BACKGROUND
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Anaplasia is a rare phenomenon seen in childhood RMS. The most common histologic subtype was Embryonal followed by Alveolar and spindle subtype.
DESIGN
A total of 11 cases of pediatric RMS were selected from January 2017 to June 2019 presenting at various sites. Out of 11 cases, 2 were further diagnosed as Embryonal, 2 as Alveolar, 2 as Pleomorphic, 1 as Spindle subtype and rest 4 as RMS-NOS based on morphology. All cases were positive for Desmin. The presence of cells with lobated, hyperchromatic nuclei at least three times larger than the tumor cell (anaplastic cells) was selected as the main criterion to diagnose Anaplasia.
RESULTS
Out of the total 11 cases, anaplasia was seen in 7 cases. Out of these seven, five cases showed Focal Anaplasia (FA) (71.4%) and 2 cases showed Diffuse Anaplasia (DA) (28.6%). Out of 2 cases of Embryonal RMS one exhibited focal anaplasia (50%). One case of Spindle RMS showed diffuse anaplasia, 2 cases of pleomorphic RMS showed focal anaplasia. Out of 3 cases of RMS- NOS, 2 exhibited focal anaplaisa and one displayed Diffuse anaplasia. Both Alveolar RMS had no features of anaplasia.
CONCLUSION
Presence of Anaplasia is a frequent observation in pediatric RMS. Anaplasia is often under reported in pediatric RMS. Pathologist should be more aware of this rare phenomenon.
Topics: Child; Humans; Anaplasia; Rhabdomyosarcoma; Sarcoma; Soft Tissue Neoplasms; Rhabdomyosarcoma, Alveolar
PubMed: 36308195
DOI: 10.4103/ijpm.ijpm_178_21 -
Current Issues in Molecular Biology Dec 2022This research was aimed at investigating the features of free radical activity and the parameters of glutathione metabolism in tumor tissues and the peritumoral zone at...
This research was aimed at investigating the features of free radical activity and the parameters of glutathione metabolism in tumor tissues and the peritumoral zone at different degrees of glial tumor anaplasia. We analyzed postoperative material from 20 patients with gliomas of different degrees of anaplasia. The greatest differences compared to adjacent noncancerous tissues were found in the tumor tissue: an increased amount of glutathione and glutathione-related enzymes at Grades I and II, and a decrease of these parameters at Grades III and IV. For the peritumoral zone of Grades I and II, the indices changed in different directions, while for Grades III and IV, they occurred synchronously with the tumor tissue changes. For Low Grade and High Grade gliomas, opposite trends were revealed regarding changes in the level of glutathione and the enzymes involved in its metabolism and in the free radical activity in the peritumoral zone. The content of glutathione and the enzymes involved in its metabolism decreased with the increasing degree of glioma anaplasia. In contrast, free radical activity increased. The glutathione system is an active participant in the antioxidant defense of the body and can be used to characterize the cell condition of gliomas at different stages of tumor development.
PubMed: 36547100
DOI: 10.3390/cimb44120439 -
Cancer Cytopathology Jul 2019Certain carcinomas of the thyroid gland behave aggressively resulting in increased patient morbidity and poor patient prognosis. The diagnosis of these aggressive... (Review)
Review
Certain carcinomas of the thyroid gland behave aggressively resulting in increased patient morbidity and poor patient prognosis. The diagnosis of these aggressive thyroid cancer subtypes is sometimes challenging and subject to increased interobserver variability. This review deals with the cytological features of such tumors including aggressive variants of papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. These malignancies fall into 2 groups based on their cytomorphology: those that exhibit distinct microscopic features (eg, nuclear findings typical of classical papillary thyroid carcinoma or marked anaplasia) and those that present with more subtle cytologic features (eg, nuclear pseudostratification, "soap bubble" nuclei, supranuclear or subnuclear cytoplasmic vacuoles, rosette-like structures, hobnail cells). We review the literature regarding these aggressive thyroid cancers and highlight important phenotypic characteristics that can be useful for their diagnosis based on fine needle aspiration.
Topics: Adenocarcinoma, Follicular; Biopsy, Fine-Needle; Diagnosis, Differential; Humans; Prognosis; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Gland; Thyroid Neoplasms
PubMed: 31150164
DOI: 10.1002/cncy.22136 -
JAMA Ophthalmology Jan 2022High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma,...
IMPORTANCE
High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving.
OBJECTIVE
To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world.
DESIGN, SETTING, AND PARTICIPANTS
An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers.
INTERVENTION
Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma.
MAIN OUTCOMES AND MEASURES
High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis.
RESULTS
Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis.
CONCLUSIONS AND RELEVANCE
Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.
Topics: Eye Enucleation; Humans; Infant; Neoplasm Invasiveness; Optic Nerve Injuries; Prospective Studies; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Risk Factors; Surveys and Questionnaires
PubMed: 34762098
DOI: 10.1001/jamaophthalmol.2021.4732 -
European Journal of Cancer (Oxford,... Jan 2021Established prognostic indicators in rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma, include several clinicopathologic features. Among pathologic...
BACKGROUND
Established prognostic indicators in rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma, include several clinicopathologic features. Among pathologic features, anaplasia has been suggested as a potential prognostic indicator, but the clinical significance of anaplasia remains unclear.
METHODS
Patients enrolled on one of five recent Children's Oncology Group clinical trials for RMS (D9602, n = 357; D9802, n = 80; D9803, n = 462; ARST0331, n = 335; and ARST0531, n = 414) with prospective central pathology review were included in this study. Clinicopathologic variables including demographic information, risk group, histologic subtype, and anaplasia were recorded along with overall survival (OS) and failure-free survival (FFS) with failure defined by recurrence, progression, or death. The log-rank test was used to compare OS and FFS.
RESULTS
Anaplasia was more common in embryonal RMS (27% of all embryonal RMS) than other subtypes of RMS (11% for alveolar RMS, 7% for botryoid RMS, 11% for spindle cell RMS). On multivariate analyses, anaplasia was not an independent prognostic factor in RMS (OS:hazard ratio (HR) = 1.12, p = 0.43; FFS:HR = 1.07, p = 0.56) across all subtypes or within embryonal RMS only (OS:HR = 1.41, p = 0.078; FFS:HR = 1.25, p = 0.16). Among tumors with TP53 mutations, 69% had anaplasia, while only 24% of tumors with anaplasia had a tumoral TP53 mutation.
CONCLUSIONS
Anaplasia is not an independent indicator of adverse outcomes in RMS. Emerging information on the prognostic significance of TP53 mutations raises the possibility that anaplasia may be a surrogate marker of TP53 mutations in some cases. Tumoral TP53 mutation status may be investigated as a prognostic indicator in future studies.
Topics: Anaplasia; Child; Child, Preschool; Female; Humans; Infant; Male; Prognosis; Rhabdomyosarcoma; Risk Factors; Survival Analysis
PubMed: 33302115
DOI: 10.1016/j.ejca.2020.10.018 -
International Journal of Molecular... Mar 2023Glioblastoma multiforme (GBM) is a primary brain tumor that is very aggressive, resistant to treatment, and characterized by a high degree of anaplasia and... (Review)
Review
Glioblastoma multiforme (GBM) is a primary brain tumor that is very aggressive, resistant to treatment, and characterized by a high degree of anaplasia and proliferation. Routine treatment includes ablative surgery, chemotherapy, and radiotherapy. However, GMB rapidly relapses and develops radioresistance. Here, we briefly review the mechanisms underpinning radioresistance and discuss research to stop it and install anti-tumor defenses. Factors that participate in radioresistance are varied and include stem cells, tumor heterogeneity, tumor microenvironment, hypoxia, metabolic reprogramming, the chaperone system, non-coding RNAs, DNA repair, and extracellular vesicles (EVs). We direct our attention toward EVs because they are emerging as promising candidates as diagnostic and prognostication tools and as the basis for developing nanodevices for delivering anti-cancer agents directly into the tumor mass. EVs are relatively easy to obtain and manipulate to endow them with the desired anti-cancer properties and to administer them using minimally invasive procedures. Thus, isolating EVs from a GBM patient, supplying them with the necessary anti-cancer agent and the capability of recognizing a specified tissue-cell target, and reinjecting them into the original donor appears, at this time, as a reachable objective of personalized medicine.
Topics: Humans; Glioblastoma; Cell Line, Tumor; Brain Neoplasms; Neoplasm Recurrence, Local; Extracellular Vesicles; Tumor Microenvironment
PubMed: 36902314
DOI: 10.3390/ijms24054883 -
Hormones & Cancer Feb 2015Anaplastic thyroid carcinoma is the least common form of thyroid cancer; however, it accounts for the majority of deaths associated with this family of malignancies. A... (Review)
Review
Anaplastic thyroid carcinoma is the least common form of thyroid cancer; however, it accounts for the majority of deaths associated with this family of malignancies. A number of genetically engineered immunocompetent mouse models recapitulating the genetic and histological features of anaplastic thyroid cancer have been very recently generated and represent an invaluable tool to dissect the mechanisms involved in the progression from indolent, well-differentiated tumors to aggressive, undifferentiated carcinomas and to identify novel therapeutic targets. In this review, we focus on the relevant characteristics associated with these models and on what we have learned in terms of anaplastic thyroid cancer biology, genetics, and response to targeted therapy.
Topics: Anaplasia; Animals; Disease Models, Animal; Humans; Mice; Mitogen-Activated Protein Kinases; Neoplasm Grading; PTEN Phosphohydrolase; Patched Receptors; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Receptors, Cell Surface; Signal Transduction; Thyroid Neoplasms
PubMed: 25420535
DOI: 10.1007/s12672-014-0208-8 -
Advances in Cancer Diagnosis: Bio-Electrochemical and Biophysical Characterizations of Cancer Cells.Micromachines Aug 2022Cancer is a worldwide leading cause of death, and it is projected that newly diagnosed cases globally will reach 27.5 million each year by 2040. Cancers (malignant... (Review)
Review
Cancer is a worldwide leading cause of death, and it is projected that newly diagnosed cases globally will reach 27.5 million each year by 2040. Cancers (malignant tumors), unlike benign tumors are characterized by structural and functional dedifferentiation (anaplasia), breaching of the basement membrane, spreading to adjacent tissues (invasiveness), and the capability to spread to distant sites (metastasis). In the cancer biology research field, understanding and characterizing cancer metastasis as well as features of cell death (apoptosis) is considered a technically challenging subject of study and clinically is very critical and necessary. Therefore, in addition to the cytochemical methods traditionally used, novel biophysical and bioelectrochemical techniques (e.g., cyclic voltammetry and electrochemical impedance spectroscopy), atomic force microscopy, and electron microscopic methods are increasingly being deployed to better understand these processes. Implementing those methods at the preclinical level enables the rapid screening of new anticancer drugs with understanding of their central mechanism for cancer therapy. In this review, principles and basic concepts of new techniques suggested for metastasis, and apoptosis examinations for research purposes are introduced, along with examples of each technique. From our recommendations, the privilege of combining the bio-electrochemical and biosensing techniques with the conventional cytochemical methods either for research or for biomedical diagnosis should be emphasized.
PubMed: 36144024
DOI: 10.3390/mi13091401