-
PloS One 2018To study the presence of 9p deletion and p16, cyclin D1 and Myc expression and their respective diagnostic and prognostic interest in oligodendrogliomas.
OBJECTIVE
To study the presence of 9p deletion and p16, cyclin D1 and Myc expression and their respective diagnostic and prognostic interest in oligodendrogliomas.
METHODS
We analyzed a retrospective series of 40 consecutive anaplastic oligodendrogliomas (OIII) from a single institution and compared them to a control series of 10 low grade oligodendrogliomas (OII). Automated FISH analysis of chromosome 9p status and immunohistochemistry for p16, cyclin D1 and Myc was performed for all cases and correlated with clinical and histological data, event free survival (EFS) and overall survival (OS).
RESULTS
Chromosome 9p deletion was observed in 55% of OIII (22/40) but not in OII. Deletion was highly correlated to EFS (median = 29 versus 53 months, p<0.0001) and OS (median = 48 versus 83 months, p<0.0001) in both the total cohort and the OIII population. In 9p non-deleted oligodendrogliomas, p16 hyperexpression correlated with a shorter OS (p = 0.02 in OII and p = 0.0001 in OIII) whereas lack of p16 expression was correlated to a shorter EFS and OS in 9p deleted OIII (p = 0.001 and p = 0.0002 respectively). Expression of Cyclin D1 was significantly higher in OIII (median expression 45% versus 14% for OII, p = 0.0006) and was correlated with MIB-1 expression (p<0.0001), vascular proliferation (p = 0.002), tumor necrosis (p = 0.04) and a shorter EFS in the total cohort (p = 0.05). Hyperexpression of Myc was correlated to grade (median expression 27% in OII versus 35% in OIII, p = 0.03), and to a shorter EFS in 9p non-deleted OIII (p = 0.01).
CONCLUSION
Chromosome 9p deletion identifies a subset of OIII with significantly worse prognosis. The combination of 9p status and p16 expression level identifies two distinct OIII populations with divergent prognosis. Hyperexpression of Bcl1 and Myc appears highly linked to anaplasia but the prognostic value is unclear and should be investigated further.
Topics: Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 9; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Oligodendroglioma; Proto-Oncogene Proteins c-myc; Survival Rate
PubMed: 29489901
DOI: 10.1371/journal.pone.0193213 -
Annals of Medicine and Surgery (2012) Jul 2023The most common malignant tumors of the uterus are endometrioid adenocarcinomas (EA). Their prognosis depends on the qualitative characteristics of the neoplastic cells...
UNLABELLED
The most common malignant tumors of the uterus are endometrioid adenocarcinomas (EA). Their prognosis depends on the qualitative characteristics of the neoplastic cells and their stroma. The neovascularization of EA tissues and level of microvascular density (MVD) influence tumor progression. Our study aims to establish the relationship between MVD in EA tissue and the histological and immunohistochemical features of tumors.
MATERIALS AND METHODS
The authors studied 30 cases of endometrial ЕА and compared their histological and immunohistochemical characteristics with the MVD of tumor tissues.
RESULTS
Our study indicated that MVD in EA tissue depends on the grade of the tumors and their FIGO stage. Increased MVD was correlated with a depression of E-cadherin and PR expression and enhanced expression of VEGF and Ki-67. MVD enhancement during VEGF overexpression is a manifestation of the functional activity of these proteins. The increase in MVD was accompanied by more frequent metastasis of the EA to the lymph nodes.
CONCLUSION
EA progression is accompanied by qualitative and quantitative variations of parenchymal and stromal patterns of tumors. Dedifferentiation of EA leads to overexpression of VEGF, which becomes diffuse in tumors cells, resulting in an increase of adenocarcinomas' MVD and their metastatic potential. Correlations between histological and immunohistochemical features of EAs indicate the synchronicity of the occurrence and progression of morphological and immunological anaplasia, which can be used in predicting the course of the disease.
PubMed: 37427185
DOI: 10.1097/MS9.0000000000000939 -
Oncotarget Mar 2015Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy...
Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies. We describe parallel evolution of genomic copy number gain and point mutation of MYCN in the contralateral tumours of a remarkable bilateral case in which independent contralateral mutations of TP53 also evolve over time. We report a second bilateral case in which MYCN gain is a germline aberration. Our results suggest a significant role for MYCN dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN gain is prognostically significant, and suggest that the novel P44L somatic variant is likely to be an activating mutation.
Topics: DNA Methylation; DNA Mutational Analysis; Disease-Free Survival; Exome; Gene Dosage; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, myc; Genes, p53; Humans; Kaplan-Meier Estimate; Kidney Neoplasms; Mutation; Neoplasm Recurrence, Local; Oligonucleotide Array Sequence Analysis; Point Mutation; Polymorphism, Single Nucleotide; Prognosis; Proto-Oncogene Mas; Proto-Oncogene Proteins c-myc; Tumor Suppressor Protein p53; Wilms Tumor
PubMed: 25749049
DOI: 10.18632/oncotarget.3377 -
Scientific Reports Aug 2021With the rising life expectancy and availability of neuroimaging, increased number of older patients will present with diffuse and anaplastic gliomas. The aim of our...
With the rising life expectancy and availability of neuroimaging, increased number of older patients will present with diffuse and anaplastic gliomas. The aim of our study was therefore to investigate age-related prognostic clinical, neuropathological and radiological features of lower-grade gliomas. All consecutive patients with diffuse or anaplastic glioma WHO grade 2 and 3 who underwent first tumor resection between 2010 and 2018, were selected from the institutional neuro-oncological database and evaluated. The mean age of 55 males and 44 females was 46 years (SD ± 16). Wild-type IDH1 (p = 0.012), persistent nuclear ATRX expression (p = 0.012) and anaplasia (p < 0.001) were significantly associated with higher age. The CE volume before resection was found to be increased in older patients (r = 0.42, p < 0.0001), and CE rate was higher in the IDH wild-type population only (p = 0.02). The extent of resection did not differ with age. Overall, one year of life resulted in a PFS reduction of 9 days (p = 0.047); in IDH sub-group analysis, this dependency was confirmed only in wild-type tumors (p = 0.05). OS was significantly reduced in older patients (p = 0.033). In conclusion, behavior and prognosis of WHO grade 2 and 3 glioma were unfavorable in correlation to patient's age, even if the extent of resection was comparable. Older age imparted a poorer PFS and higher CE rate only in the IDH wild-type population.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Brain Neoplasms; Female; Glioma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Neoplasm Grading; Progression-Free Survival; Proportional Hazards Models; Survival Rate; Treatment Outcome; World Health Organization; Young Adult
PubMed: 34462493
DOI: 10.1038/s41598-021-96832-4 -
Asian Journal of Surgery Jun 2022To investigate the outcomes of patients with mucoepidermoid carcinoma of the palate undergoing pedicled facial-submental artery island flap (FSIF) reconstruction...
OBJECTIVE
To investigate the outcomes of patients with mucoepidermoid carcinoma of the palate undergoing pedicled facial-submental artery island flap (FSIF) reconstruction following resection.
PATIENTS AND METHODS
41 patients with early stage disease and 9 patients with advanced-stage disease underwent radical excision and neck dissection. 37 IIb, 4 class IIa and 9 IIIb maxillary defects were reconstructed with FSIF, folded FSIF or folded FSIF with titanium mesh respectively. The skin paddles were 3 × 8 to 5 × 15 cm and 3 × 8 to 5 × 14 cm, respectively. 5 patients with high grade disease were treated with cobalt 60 adjuvant radiotherapy after operation.
RESULTS
One flap failure occurred, yielding a success rate of 98.0% in the reconstruction of palate II and III defects with FSIF or titanium mesh. The patients were seen for follow-up for 16-60 months postoperative. 76.0% patients alive with no disease (AND); 14.0% patients alive with disease (AD) and 10.0% died of disease (DD). Rates of AND, AD and DD differed significantly according to histopathologic grade and TNM stage (P < 0.001); rates of AND, AD and DD differed obviously according to necrosis of the tumors lymph node metastasis, and tumour cell anaplasia and treatment (P < 0.05).
CONCLUSIONS
Radical resection with wide safety margins of normal tissues including neck dissection is the mainstay of treatment modality. The patients with high grade disease should be treated with postoperative radiotherapy. The FSIF is a reliable and safe method for repairing Brown class II maxillary defects.
Topics: Carcinoma, Mucoepidermoid; Humans; Palate; Plastic Surgery Procedures; Salivary Glands, Minor; Surgical Flaps; Titanium
PubMed: 34627688
DOI: 10.1016/j.asjsur.2021.08.039 -
Journal of Kidney Cancer and VHL 2021Wilms' tumor (WT) in adults is a rare neoplasm. Only a few reports are available in the literature. The tumor often masquerades as renal cell carcinoma (RCC). For...
Wilms' tumor (WT) in adults is a rare neoplasm. Only a few reports are available in the literature. The tumor often masquerades as renal cell carcinoma (RCC). For accurate reporting, histopathological examination (HPE) plays a vital role in early diagnosis and prompt administration of multimodality treatment helps to improve the prognosis. We comprehensively analyzed five cases of adult WT presenting in the third to fifth decade with flank pain, hematuria, fever, and palpable lump. After complete clinical, biochemical, radiological, and HPE evaluation, tumor was staged and treatment was planned accordingly. Patients with low-stage WT were treated with open radical nephrectomy and chemotherapy. One of the patients diagnosed with inferior vena cava (IVC) thrombus apart from the above treatment also underwent IVC thrombectomy. Another young male presenting with distant metastasis (stage IV) and focal anaplasia on histology received preoperative chemotherapy and then planned for surgery. Unfortunately, the tumor being unresectable, second-line chemotherapy was given but he ultimately succumbed to death. All other patients are on regular follow-up and disease-free. Adult nephroblastoma is a rare clinical entity with hostile behavior. The presence of IVC thrombus is not a contraindication to surgery. Although the management strategy as per pediatric protocol by the inclusion of multimodality approach improves survival, still the overall prognosis in adults is dismal. There is a need for a standardized treatment protocol to encourage a homogenous approach for this rare disease and thereby improve survival.
PubMed: 34322362
DOI: 10.15586/jkcvhl.v8i2.186 -
Biomedicines Sep 2022This research aimed to investigate the relationships between the parameters of glutathione metabolism and the immunohistochemical characteristics of glial tumors....
This research aimed to investigate the relationships between the parameters of glutathione metabolism and the immunohistochemical characteristics of glial tumors. Postoperative material from 20 patients with gliomas of different grades of anaplasia was analyzed. Bioinformatic analysis of the interactions between the gliomas' immunohistochemical markers and their glutathione-dependent enzymes was carried out using the STRING, BioGrid, while Signor databases revealed interactions between such glioma markers as IDH and p53 and the glutathione exchange enzymes (glutathione peroxidase, glutathione reductase, glutathione S-transferase). The most pronounced relationship with glutathione metabolism was demonstrated by the level of the nuclear protein Ki67 as a marker of proliferative activity, and the presence of the IDH1 mutation as one of the key genetic events of gliomagenesis. The glutathione system is an active participant in the body's antioxidant defense, involving the p53 markers and MGMT promoter methylation. It allows characterization of the gliomal cells' status at different stages of tumor development.
PubMed: 36289655
DOI: 10.3390/biomedicines10102393 -
Neuro-oncology Advances 2021Anaplastic pleomorphic xanthoastrocytoma (APXA) is a rare subtype of CNS astrocytoma. They are generally treated as high-grade gliomas; however, uncertainty exists...
BACKGROUND
Anaplastic pleomorphic xanthoastrocytoma (APXA) is a rare subtype of CNS astrocytoma. They are generally treated as high-grade gliomas; however, uncertainty exists regarding the optimal therapy. Here, we report on 3 pediatric cases of APXA.
METHODS
Our institutional database was queried for cases of APXA and 3 cases were identified. Surgical samples were processed for methylation profiling and chromosomal microarray analysis. Methylation data were uploaded to the online CNS tumor classifier to determine methylation-based diagnoses to determine copy number variations (CNVs).
RESULTS
Two patients were male, 1 female, and all were aged 12 years at diagnosis. All underwent a gross total resection (GTR) and were diagnosed with an APXA. Immunohistochemical analysis demonstrated that 2 cases were BRAF V600E positive. Methylation-based tumor classification supported the APXA diagnosis in all cases. CNV analyses revealed homozygous deletions in all and chromosome 9p loss in 2 cases. All patients received radiation therapy (54 Gy in 30 fractions) with concurrent temozolomide. Two patients received maintenance chemotherapy with temozolomide and lomustine for 6 cycles as per the Children's Oncology Group ACNS0423. The third patient recurred and went on to receive a second GTR and 6 cycles of lomustine, vincristine, and procarbazine. All are alive with no evidence of disease >4 years post-treatment completion (overall survival = 100%, event free survival = 67%).
CONCLUSIONS
The natural history and optimal treatment of this rare pediatric tumor are not well understood. This case series supports the use of adjuvant chemoradiotherapy in the treatment of APXA. The genetic landscape may be informative for optimizing treatment and prognosis.
PubMed: 33543147
DOI: 10.1093/noajnl/vdaa176 -
Cancer Apr 2022Since the International Society of Paediatric Oncology Wilms' Tumour 2001 (SIOP-WT-2001) study, focal anaplastic Wilms tumors (FAWTs) have been treated as...
BACKGROUND
Since the International Society of Paediatric Oncology Wilms' Tumour 2001 (SIOP-WT-2001) study, focal anaplastic Wilms tumors (FAWTs) have been treated as intermediate-risk Wilms tumors (WTs), and diffuse anaplastic Wilms tumors (DAWTs) have been treated as high-risk tumors.
METHODS
The authors performed a retrospective analysis of preoperatively treated patients with FAWT or DAWT recruited in 2 consecutive UK Children's Cancer and Leukaemia Group WT studies.
RESULTS
One hundred twenty-one of 1237 patients (10%) had an anaplastic WT confirmed by central pathology review (CPR): 93 (77%) had DAWT, and 28 (23%) had FAWT. The 4-year event-free survival (EFS) was 51% (95% confidence interval [CI], 41%-63%) for DAWT, 88% (95% CI, 76%-100%) for FAWT, and 84% (95% CI, 82%-87%) for intermediate-risk nonanaplastic Wilms tumor (IR-non-AWT). Overall survival (OS) was 58% (95% CI, 48%-70%) for DAWT, 95% (95% CI, 86%-100%) for FAWT, and 95% (95% CI, 93%-96%) for IR-non-AWT. In a multivariate analysis, the presence of DAWT was a significant prognostic factor for both EFS and OS in stages II, III, and IV. In a multivariate analysis of unilateral DAWT, stages III and IV remained the only significant prognostic factors for both EFS and OS. In 28% of the cases, there were discrepancies affecting the recognition of anaplasia, classification (DAWT vs FAWT), or the local pathologic stage.
CONCLUSIONS
Preoperatively treated patients with FAWT had excellent outcomes in comparison with those with identically treated IR-non-AWT, whereas patients with DAWT showed significantly worse outcomes. All patients with stage I disease had comparable good outcomes, regardless of the presence/absence of anaplasia. In contrast, the presence of DAWT was associated with significantly worse outcomes for patients with stage II to V disease. Finally, significant diagnostic discrepancies emphasize the value of CPR.
LAY SUMMARY
Anaplasia is an unfavorable feature in Wilms tumor (WT), and it is classified as focal (focal anaplastic Wilms tumor [FAWT]) or diffuse (diffuse anaplastic Wilms tumor [DAWT]). This study reports the outcomes of patients with FAWT and DAWT who were, for the first time, treated differently. Patients with FAWT received less intensive treatment, and their outcomes were comparable to the outcomes of patients with identically treated nonanaplastic WT. Patients with stage I DAWT also had good outcomes when they were treated without radiotherapy, whereas patients with stage II to V DAWT had poor outcomes despite more intensive treatment.
Topics: Child; Humans; Infant; Kidney Neoplasms; Neoplasm Staging; Prognosis; Retrospective Studies; United Kingdom; Wilms Tumor
PubMed: 35119702
DOI: 10.1002/cncr.34107 -
Biomedicines Apr 2022This research aimed to investigate the interrelationship of carbohydrate metabolism parameters and immunohistochemical characteristics of glial tumors. Tumor tissue,...
This research aimed to investigate the interrelationship of carbohydrate metabolism parameters and immunohistochemical characteristics of glial tumors. Tumor tissue, peritumoral area, and adjacent noncancerous tissue fragments of 20 patients with gliomas of varying degrees of anaplasia were analyzed. The greatest differences in the carbohydrate metabolism compared to adjacent noncancerous tissues were identified in the tumor tissue: reduction in the levels of lactate and glycogen synthase kinase-3β. Significant differences with adjacent noncancerous tissues for the peritumoral zone were not found. The activity of the carbohydrate metabolism enzymes was different depending on the immunohistochemical glioma profile, especially from Ki 67 level. Bioinformatic analysis of the interactions of immunohistochemical markers of gliomas and carbohydrate metabolism enzymes using the databases of STRING, BioGrid, and Signor revealed the presence of biologically significant interactions with glycogen synthase kinase 3β, hexokinase, glucose-6-phosphate dehydrogenase, and transketolase. The established interconnection of glycolysis with methylation of the promoter of O-6-methylguanine-DNA-methyltransferase (MGMT) of gliomas can be used to increase chemotherapy efficiency.
PubMed: 35625744
DOI: 10.3390/biomedicines10051007