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1.
BMC Cancer ; 23(1): 118, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737737

RESUMO

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples. RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica
2.
Malays J Pathol ; 37(1): 19-24, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25890609

RESUMO

Loss of E-cadherin, a 120 kDA transmembrane glycoprotein responsible for cell-cell adhesion, is one of the hallmarks of epithelial-mesenchymal-transition (EMT). E-cadherin expression was immunohistochemically studied in 94 histopathologically re-confirmed colorectal carcinomas (CRC) using a monoclonal antibody to E-cadherin (Dako: Clone NCH-38) on a Ventana Benchmark XT automated system. Each case was assessed for E-cadherin immunopositivity at two separate locations viz the tumour centre (TC) as well as the infiltrating front (IF). Expression was semiquantitated for proportion of immunopositive malignant cells as 0 (negative), 1 (1-25% staining), 2 (26-50% staining), 3 (51-75% staining) and 4 (>75% staining) and staining intensity: 0 (negative), 1 (weak), 2 (moderate) and 3 (strong). The final histoscore of E-cadherin immunopositivity was arbitrarily computed as proportion of immunopositivity multiplied by staining intensity of the malignant cells. E-cadherin histoscores were significantly lower at the IF (4.5±2.5) compared with TC (10.7±2.4). Furthermore, the histoscores were significantly reduced at the IF of 49 TNM III+IV tumours (3.6±2.5) compared with 45 II+III CRC (5.4±2.2). Reduction of E-cadherin expression was also noted in the 23 high grade (TC=8.6±3.2; IF=2.6±2.3) compared with 71 low grade tumours (TC=11.4±1.5; IF=5.1±2.3). E-cadherin is downregulated at the infiltrating front of CRC, possibly marking for EMT at this location. The downregulation is further enhanced amongst late stage and high grade tumours compared with earlier stage and low grade tumours; findings which are similar to that noted in CRC of other populations.


Assuntos
Biomarcadores Tumorais/análise , Caderinas/análise , Carcinoma/química , Neoplasias Colorretais/química , Antígenos CD , Biópsia , Carcinoma/secundário , Neoplasias Colorretais/patologia , Regulação para Baixo , Humanos , Imuno-Histoquímica , Malásia , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes
3.
J Clin Microbiol ; 52(9): 3468-70, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24989613

RESUMO

We report a rare and unusual case of invasive Enterobius vermicularis infection in a fallopian tube. The patient was a 23-year-old Malaysian woman who presented with suprapubic pain and vaginal bleeding. A clinical diagnosis of ruptured right ovarian ectopic pregnancy was made. She underwent a laparotomy with a right salpingo-oophorectomy. Histopathological examination of the right fallopian tube showed eggs and adult remnants of E. vermicularis, and the results were confirmed using PCR and DNA sequencing.


Assuntos
Enterobíase/diagnóstico , Enterobius/isolamento & purificação , Complicações Parasitárias na Gravidez/diagnóstico , Gravidez Ectópica/diagnóstico , Salpingite/diagnóstico , Animais , DNA de Helmintos/química , DNA de Helmintos/genética , Enterobíase/patologia , Enterobíase/cirurgia , Tubas Uterinas/parasitologia , Tubas Uterinas/patologia , Feminino , Histocitoquímica , Humanos , Laparoscopia , Malásia , Ovariectomia , Reação em Cadeia da Polimerase , Gravidez , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/patologia , Complicações Parasitárias na Gravidez/cirurgia , Salpingectomia , Salpingite/parasitologia , Salpingite/patologia , Salpingite/cirurgia , Análise de Sequência de DNA , Adulto Jovem
4.
BMJ Case Rep ; 17(1)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216171

RESUMO

Bronchogenic cyst is a congenital abnormality arising from the tracheobronchial system. Localisation of such cysts in the head and neck region is rare. We report a girl in her early childhood with a painless enlarging right lateral neck mass diagnosed with a branchial cleft cyst based on clinical and radiological MRI findings. An incidental finding of a cervical bronchogenic cyst was made on the final histopathological specimen. Although rare, bronchogenic cysts should be considered as differential diagnoses for paediatric patients' lateral and midline cervical masses.


Assuntos
Branquioma , Cisto Broncogênico , Lesões Pré-Cancerosas , Neoplasias do Colo do Útero , Feminino , Humanos , Criança , Pré-Escolar , Cisto Broncogênico/diagnóstico por imagem , Cisto Broncogênico/cirurgia , Pescoço/diagnóstico por imagem , Pescoço/patologia , Branquioma/diagnóstico , Imageamento por Ressonância Magnética , Diagnóstico Diferencial , Lesões Pré-Cancerosas/patologia , Neoplasias do Colo do Útero/patologia
5.
Ear Nose Throat J ; : 1455613231212597, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-37997797

RESUMO

Cavernous hemangioma is a noncancerous vascular growth that arises from different parts of the head and neck region. However, parapharyngeal space contributes a very small percentage for its occurrence. We present a case of right parapharyngeal cavernous hemangioma, a very rare clinical presentation. This is a 57-year-old female presented with throat discomfort for 3 months. Examination finding showed a soft, diffuse, and non-pulsating mass over the right upper jugulodigastric region. A contrasted computed topographic scan revealed multiple calcifications in right parapharyngeal space. T2-weighted magnetic resonance imaging showed right parapharyngeal space mass with high signal and multiple phleboliths and dynamic angiogram unremarkable. Surgical resection done via transcervical approach and histopathological report revealed cavernous hemangioma with calcified thrombi. In conclusion, surgical intervention is the mainstay treatment and transcervical approach which is adopted in this case is the commonest approach used in surgical resection of cavernous hemangioma.

6.
Case Rep Surg ; 2023: 3114843, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36999167

RESUMO

Metastatic lesions to the breast from extramammary malignant neoplasms are rare and reported account for 0.5-6.6% of all breast malignancies. Distant metastasis of thymoma is even rarer, especially to extrathoracic regions. We reported a woman with invasive malignant thymoma postneoadjuvant and resection of the thymoma, who developed breast metastasis 7 years later. Breast imaging showed high-density lesion with no intralesional microcalcifications and no significant axillary lymphadenopathy. Core biopsy and histopathology proved the lesion to be metastatic thymic carcinoma. Despite rarity, breast lumps with underlying extramammary malignancy should raise the suspicious of breast metastasis.

7.
Cancers (Basel) ; 15(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36672402

RESUMO

Accurate diagnosis of the most common histological subtypes of small B-cell lymphomas is challenging due to overlapping morphological features and limitations of ancillary testing, which involves a large number of immunostains and molecular investigations. In addition, a common diagnostic challenge is to distinguish reactive lymphoid hyperplasia that do not require additional stains from such lymphomas that need ancillary investigations. We investigated if tissue-specific microRNA (miRNA) expression may provide potential biomarkers to improve the pathology diagnostic workflow. This study seeks to distinguish reactive lymphoid proliferation (RL) from small B-cell lymphomas, and to further distinguish the four main subtypes of small B-cell lymphomas. Two datasets were included: a discovery cohort (n = 100) to screen for differentially expressed miRNAs and a validation cohort (n = 282) to develop classification models. The models were evaluated for accuracy in subtype prediction. MiRNA gene set enrichment was also performed to identify differentially regulated pathways. 306 miRNAs were detected and quantified, resulting in 90-miRNA classification models from which smaller panels of miRNAs biomarkers with good accuracy were derived. Bioinformatic analysis revealed the upregulation of known and other potentially relevant signaling pathways in such lymphomas. In conclusion, this study suggests that miRNA expression profiling may serve as a promising tool to aid the diagnosis of common lymphoid lesions.

8.
Respirol Case Rep ; 11(7): e01181, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37350988

RESUMO

Neoadjuvant chemotherapy is a therapeutic option for potentially resectable non-small cell lung cancer (NSCLC). The role of neoadjuvant targeted therapy (NTT) remains less explored. This case highlights the use of neoadjuvant osimertinib in a case of advanced NSCLC. A 67-year-old woman had a left lower lobe lung mass measuring 5.0 × 5.1 × 7.0 cm with an enlarged subcarinal lymph node (LN) on her positron emission tomography scan. Following biopsy, a diagnosis of stage IIIB N2 (cT3N2M0) EGFR exon 19 deletion mutation-positive lung adenocarcinoma was established. NTT using osimertinib 80 mg once daily was commenced. Subsequent re-imaging at 3 months (ycT2bN2M0), 6 months (ycT1cN2M0) and 9 months showed tumour downstaging and resolution of the subcarinal LN (ycT1cN0M0). She underwent left lower lobectomy with systematic nodal dissection. All surgical specimens demonstrated no evidence of malignant cells (ypT0N0). Osimertinib could be the preferred NTT for potentially resectable NSCLC.

9.
Int J Lab Hematol ; 44(5): 907-917, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35830966

RESUMO

INTRODUCTION: Routine categorization of DLBCL patients into GCB and non-GCB groups by Hans' criteria could not accurately predict chemotherapy resistance and disease progression in patients treated with standard R-CHOP therapy. There is a need to identify better biomarker predictors to enhance assisted selection of chemotherapy regimens for DLBCL patients. AIM OF THE STUDY: To identify dysregulated miRNAs and mRNAs that are predictive of resistance to R-CHOP chemotherapy or disease progression in patients with DLBCL. METHODS: miRNA and mRNA profiling were performed on archival FFPE samples of the DLBCL patients. miRabel and miRNet bioinformatic tools were applied to determine experimental validated miRNA-mRNA target interaction. The significance of the genomic predictive values was assessed using adjusted odds ratios (AOR) and 95% confidence intervals (CI). RESULTS: 19/36 were R-CHOP therapy-resistant whilst 17/36 were R-CHOP therapy-sensitive. Ten dysregulated miRNAs and 12 dysregulated mRNAs were identified in therapy-resistant DLBCL patients. These dysregulated miRNAs and mRNA cause therapy resistance and disease progression in DLBCL patients, most likely via upregulation of the anti-apoptotic protein bcl2, activation of the JAK/STAT signalling pathway and dysregulation of p53 pathway. Downregulation of hsa-miR-548d-3p and overexpression of HOXA9 mRNA were significantly associated with therapy resistance and disease progression in DLBCL patients [hsa-miR-548d-3p AOR: 0.258, 95%CI: 0.097-0.684, p = 0.006]. CONCLUSION: DLBCL patients with downregulation of hsa-miR-548d-3p and overexpression of HOXA9 mRNA are more likely to experience R-CHOP therapy resistance and disease progression.


Assuntos
Proteínas de Homeodomínio/metabolismo , Linfoma Difuso de Grandes Células B , MicroRNAs , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida , Progressão da Doença , Regulação para Baixo , Doxorrubicina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Prednisona , Prognóstico , RNA Mensageiro , Rituximab , Vincristina
10.
Natl Sci Rev ; 9(3): nwab192, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35382356

RESUMO

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

11.
Cancer Manag Res ; 12: 5439-5450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753961

RESUMO

BACKGROUND: This study aims to determine the predictors of acquired exon 20 T790M mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing epidermal growth factor receptor (EGFR) mutation following the failure of first- or second-generation EGFR-tyrosine kinase inhibitor (TKI). METHODS: This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017. RESULTS: A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84-6.25, p = 0.104). CONCLUSION: The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations.

12.
PeerJ ; 6: e5530, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30221090

RESUMO

BACKGROUND: Except for a few studies with contradictory observations, information is lacking on the possibility of association between DNA mismatch repair (MMR) status and the presence of cancer stem cells in colorectal carcinoma (CRC), two important aspects in colorectal carcinogenesis. METHODS: Eighty (40 right-sided and 40 left-sided) formalin-fixed, paraffin-embedded primary CRC were immunohistochemically studied for CD133, a putative CRC stem cell marker, and MMR proteins MLH1, MSH2, MSH6 and PMS2. CD133 expression was semi-quantitated for proportion of tumor immunopositivity on a scale of 0-5 and staining intensity on a scale of 0-3 with a final score (units) being the product of proportion and intensity of tumor staining. The tumor was considered immunopositive only when the tumor demonstrated moderate to strong intensity of CD133 staining (a decision made after analysis of CD133 expression in normal colon). Deficient MMR (dMMR) was interpreted as unequivocal loss of tumor nuclear staining for any MMR protein despite immunoreactivity in the internal positive controls. RESULTS: CD133 was expressed in 36 (90.0%) left-sided and 28 (70.0%) right-sided tumors (p < 0.05) and CD133 score was significantly higher in left- (mean ± SD = 9.6 ± 5.3 units) compared with right-sided tumors (mean ± SD = 6.8 ± 5.6 units) p < 0.05). dMMR was noted in 14 (35%) right-sided and no (0%) left-sided CRC. When stratified according to MMR status, dMMR cases showed a lower frequency of CD133 expression (42.9%) and CD133 score (mean ± SD = 2.5 ± 3.6 units) compared with pMMR tumors on the right (frequency = 84.6%; mean score ± SD = 9.2 ± 5.0 units) as well as pMMR tumors on the left (frequency = 90.0%; mean score ± SD = 9.6 ± 5.3 units) (p < 0.05). Interestingly, frequencies of CD133 immunoreactivity and CD133 scores did not differ between pMMR CRC on the right versus the left (p > 0.05). CONCLUSION: Proficient MMR correlated with high levels of CD133-marked putative cancer stem cells in both right- and left-sided tumors, whereas significantly lower levels of CD133-marked putative cancer stem cells were associated with deficient MMR status in colorectal carcinomas found on the right.

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