OBJECTIVE: This study investigated UTX and JMJD3 protein expression patterns in UC and assess their clinical significance.
PATIENTS AND METHODS: Immunohistochemistry (IHC) method was performed on formalin-fixed paraffin-embedded (FFPE) of UC tissues and compared to the normal bladder tissues from the autopsy specimen. The staining intensity of FFPE tissues were captured with the nuclear and overall positive pixels quantified using Aperio ImageScope software.
RESULTS: JMJD3 protein uptake was present in both nucleus and cytoplasm but UTX protein was predominantly seen in the cytoplasm of UC tissue. UTX was under expressed whereas JMJD3 was over expressed in UC compared to normal bladder. UTX and JMJD3 were not related to clinical stage and grade. However, significant association between JMJD3 expression and invasiveness of tumour (p<0.05) was noted, especially in MIBC group (88.9%). UTX and JMJD3 did not yield any significance as prognostic factors for diseasespecific survival.
CONCLUSIONS: Low expression of UTX protein in UC may indicate possible loss of its tumour suppressor activity and higher JMJD3 protein expression may indicate oncogenic activity. Hence, JMJD3 protein could be a potential diagnostic biomarker in detecting bladder UC of higher stages. Further investigation needed to study the dysregulation of this protein expression with associated gene expression.
MATERIALS AND METHODS: Formalin-fixed paraffinembedded (FFPE) blocks of muscle-invasive bladder cancer patients receiving cisplatin-based chemotherapy between January 2010 to December 2020 were traced. Immunohistochemistry staining was performed on traced blocks using antibodies to e-cadherin, vimentin and actin, and p53.
RESULTS: p53 and e-cadherin were stained positive in most cases (p=0.515 and 0.242 respectively), although e-cadherin showed stronger positive expression in pre-cisplatin receiving MIBC cases. All the cases stained negative for actin and vimentin except for faint staining observed in one pre-cisplatin case.
CONCLUSION: Although this study does not show a significant correlation between EMT markers and p53 with cisplatin-responsiveness in MIBC patients, the results serve as preliminary findings on the heterogeneous outcomes of molecular staining in the Malaysian MIBC patient cohort.
PATIENTS AND METHODS: We retrospectively reviewed data from patients below 18 years of age with iGCTs treated at the University Malaya Medical Center (UMMC) from 1998 to 2017.
RESULTS: Thirty-four patients were identified, with a median follow-up of 3.54 years. Sixteen (47%) patients had pure germinoma tumors (PGs), and the remaining patients had nongerminomatous germ cell tumors (NGGCTs). The median age was 12 years, with a male:female ratio of 4.7:1. Abnormal vision, headache with vomiting, and diabetes insipidus were the commonest presenting symptoms. Twenty-eight patients received initial surgical interventions, 24 were treated with chemotherapy, and 28 received radiotherapy. Eight patients experienced relapses. The 5- and 10-year event-free survival rates were similar at 61.1%±12.6% and 42.9%±12.1% for PG and NGGCT, respectively. The 5- and 10-year overall survival rates were the same at 75.5%±10.8% and 53.3%±12.3% for PG and NGGCT, respectively. Four patients died of treatment-related toxicity. Most of the survivors experienced good quality of life with satisfactory neurologic status.
CONCLUSIONS: The survival rate of childhood iGCTs in UMMC was inferior to that reported in developed countries. Late diagnosis, poor adherence to treatment, and treatment-related complications were the contributing factors. Although these results highlight a single institution experience, they most likely reflect similar treatment patterns, outcomes, and challenges in other centers in Malaysia.
METHODS: We retrospectively reviewed the clinical data of pediatric patients (aged <18 years) with CNS tumors diagnosed and treated in the Pediatric Hematology-Oncology Division at the University Malaya Medical Center from 2008 to 2019. We also conducted a web-based survey of the core members of the multidisciplinary team to evaluate the impact of the MDTMs.
RESULTS: During the pre-MDTM era (2008-2012), 29 CNS tumors were diagnosed and treated, and during the MDTM era (2014-2019), 49 CNS tumors were diagnosed and treated. The interval for histologic diagnosis was significantly shorter during the MDTM era (p=0.04), but the interval from diagnosis to chemotherapy or radiotherapy and the 5-year overall survival of the 78 patients did not improve (62.1% ± 9.0% vs. 68.8% ± 9.1%; p=0.184). However, the 5-year overall survival of patients with medulloblastoma or rare tumors significantly improved in the MDTM era (p=0.01). Key factors that contributed to delayed treatment and poor outcomes were postoperative complications, the facility's lack of infrastructure, poor parental education about early treatment, cultural beliefs in alternative medicine, and infection during chemotherapy. Eighteen clinicians responded to the survey; they felt that the MDTMs were beneficial in decision-making and enhanced the continuity of coordinated care.
CONCLUSION: MDTMs significantly reduced the diagnostic interval and improved the overall outcomes. However, delayed treatment remains a major challenge that requires further attention.
METHODS: The preoperative MRI of a 54-year-old woman revealed a sellar lesion (28 × 19 × 16 mm), presumably a pituitary macroadenoma, and a second extra-axial lesion (22 × 36 × 20 mm) expanding from the tuberculum sellae to the planum sphenoidale with encasement of the anterior communicating complex, presumably a meningioma. We used intraoperative MRI to assess the extent of the resection before reconstructing the large skull base defect. Furthermore, we systematically reviewed pertinent articles retrieved by a PubMed/Embase database search between 1961 and December 2018.
RESULTS: Out of 63 patients with synchronous tumors reported in 43 publications, we found 3 patients in which the tumor was removed by EEA. In these 3 patients and the presented case, the resection of both lesions was successful, without major approach-related morbidity or mortality. More extensive removal of endonasal structures to gain an adequate tumor exposure was not necessary. We did not find any previous reports describing the benefits of intraoperative MRI in the presented setting.
CONCLUSIONS: In the rare case of a synchronous meningioma and pituitary adenoma of the sellar region, intraoperative MRI might be beneficial in confirming residual disease before skull base reconstruction, and therefore radiologic follow-up.
Objective: The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant.
Results: There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC.
Conclusion: In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.
MATERIALS AND METHODS: Following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, online searches of multiple databases were performed to retrieve articles from their inception until December 2017. Inclusion criteria included all English-based original articles of immunohistochemistry (IHC) studies investigating CAIX expression in human RCC tissue. Four articles were finally selected for meta-analysis with a total of 1964 patients. Standard meta-analysis methods were applied to evaluate the role of CAIX in RCC prognosis. The relative risk (RR) and its 95% confidence interval (CI) were recorded for the association between biomarker and prognosis, and data were analysed using MedCalc statistical software.
RESULTS: The meta-analysis showed that high CAIX expression was associated with low tumour stage (RR 0.90%, 95% CI 0.849-0.969, p= 0.004), low tumour grade (RR 0.835%, 95% CI 0.732-0.983, p= 0.028), absence of nodal involvement (RR 0.814%, 95% CI 0.712-0.931, p= 0.003) and better ECOS-PS index (RR 0.888%, 95% CI 0.818-0.969, p= 0.007). The high tissue CAIX expression in RCC is hence an indication of an early malignancy with a potential to predict favourable disease progression and outcome.
CONCLUSION: The measurement of this marker may be beneficial to determine the course of the illness. It is hoped that CAIX can be developed as a specific tissue biomarker for RCC in the near future.
Methods: The effect of palbociclib was evaluated in a panel of well-characterized OSCC cell lines by cell proliferation assays and further confirmed by in vivo evaluation in xenograft models. PIK3CA-mutant isogenic cell lines were used to investigate the effect of PIK3CA mutation towards palbociclib response.
Results: We demonstrated that 80% of OSCC cell lines are sensitive to palbociclib at sub-micromolar concentrations. Consistently, palbociclib was effective in controlling tumor growth in mice. We identified that palbociclib-resistant cells harbored mutations in PIK3CA. Using isogenic cell lines, we showed that PIK3CA mutant cells are less responsive to palbociclib as compared to wild-type cells with concurrent upregulation of CDK2 and cyclin E1 protein levels. We further demonstrated that the combination of a PI3K/mTOR inhibitor (PF-04691502) and palbociclib completely controlled tumor growth in mice.
Conclusions: This study demonstrated the potency of palbociclib in OSCC models and provides a rationale for the inclusion of PIK3CA testing in the clinical evaluation of CDK4/6 inhibitors and suggests combination approaches for further clinical studies.
Case Description: We report a 42-year-old man, diagnosed with rosette-forming glioneuronal tumor of the fourth ventricle with a positive isocitrate dehydrogenase 1 mutation, progressed to glioblastoma after 6 years from diagnosis. We discuss the clinical history, radiological findings, and histopathological characteristic with immunohistochemistry findings observed in this unique case.
Conclusions: Despite being acceptable as benign, based on our observations in this case, there is a potential for malignant transformation of rosette-forming glioneuronal tumor. The role of isocitrate dehydrogenase 1 mutation leading to malignant transformation could not be established as our finding is novel and further prospective studies are required to prove this association.
OBJECTIVES: This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma.
METHODS: We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models.
RESULTS: In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models.
CONCLUSIONS: Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.