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1.
World J Surg ; 48(5): 1159-1166, 2024 May.
Article in English | MEDLINE | ID: mdl-38578243

ABSTRACT

BACKGROUND: Axillary lymph node dissection (ALND) in breast cancer management, necessitates a nuanced understanding of complications that may impede treatment progression. This study scrutinize the impact of Haemoblock hemostatic solution, evaluation it's potential in reducing seroma complication by controlling lymph flow and obliterating axillary dead space. METHOD: A prospective, randomized, double-blinded controlled trial was conducted with 58 patients undergoing breast conserving surgery (BCS) and ALND, stratified into two groups: Group A (ALND + Haemoblock, n = 29) and Group B (ALND + placebo, n = 29). Postoperative drainage charts were monitored, with the primary endpoint being the time to drain removal, Additionally, patients were observed for surgical site infection (SSI). RESULTS: Group A exhibited a marginally higher mean total drain output (398 +/- 205 vs. 326 +/- 198) compared to Group B, this difference did not attain statistical significance (p = 0.176). Equally, the mean time to drain removal demonstrated no discernible distinction between the two groups (6 +/- 3.0 vs. 6 +/- 3.0, Group A vs. Group B, p = 0.526). During follow up, nine patients in Group A required seroma aspiration (mean aspiration 31 +/- 73) as compared to Group B, 6 patients required aspiration (mean aspiration 12 +/- 36), p = 0.222). No notable disparity in SSI rates between the groups was identified. CONCLUSION: In conclusion, the administration of Haemoblock did not manifest a discernible effect in mitigating seroma production, hastening drain removal, or influencing SSI rates following ALND. The study underscores the intricate and multifactorial nature of seroma formation, suggesting avenues for future research to explore combined interventions and protracted follow-up periods for a more comprehensive understanding.


Subject(s)
Axilla , Breast Neoplasms , Hemostatics , Lymph Node Excision , Mastectomy, Segmental , Seroma , Humans , Seroma/prevention & control , Seroma/etiology , Female , Lymph Node Excision/adverse effects , Lymph Node Excision/methods , Middle Aged , Breast Neoplasms/surgery , Prospective Studies , Double-Blind Method , Mastectomy, Segmental/adverse effects , Mastectomy, Segmental/methods , Hemostatics/therapeutic use , Aged , Drainage , Adult , Treatment Outcome , Surgical Wound Infection/prevention & control , Surgical Wound Infection/etiology , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Postoperative Complications/epidemiology
2.
Endocrine ; 79(1): 135-142, 2023 01.
Article in English | MEDLINE | ID: mdl-36129592

ABSTRACT

AIM: Although Graves' disease (GD) is common in endocrine practices worldwide, global differences in diagnosis and management remain. We sought to assess the current practices for GD in countries across Asia and the Pacific (APAC), and to compare these with previously published surveys from North America and Europe. METHODS: A web-based survey on GD management was conducted on practicing clinicians. Responses from 542 clinicians were received and subsequently analysed and compared to outcomes from similar surveys from other regions. RESULTS: A total of 542 respondents participated in the survey, 515 (95%) of whom completed all sections. Of these, 86% were medical specialists, 11% surgeons, and 3% nuclear medicine physicians. In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (68%) during initial work-up. Thyroid ultrasound is requested by about half of respondents (53%), while the use of nuclear medicine scans is limited. The preferred first-line treatment is anti-thyroid drug (ATD) therapy (79%) with methimazole (MMI) or carbimazole (CBZ), followed by radioiodine (RAI; 19%) and surgery (2%). In case of surgery, one-third of respondents would opt for a subtotal rather than a total thyroidectomy. In case of mild Graves orbitopathy (GO), ATDs (67%) remains the preferred treatment, but a larger proportion of clinicians prefer surgery (20%). For a patient with intention to conceive, the preferred treatment pattern remained unchanged, although propylthiouracil (PTU) became the preferred ATD-agent during the first trimester. In comparison to European and American practices, marked differences were noted in the relatively infrequent usage of nuclear medicine scans and the overall higher use of a ATDs and ß-blockers and adjunctive ATD-treatment during RAI in the APAC-group. CONCLUSION: Although regional differences regarding the diagnosis and management of GD are apparent in this first pan-Asia-Pacific survey, this study reveals the overall approach to the management of this disease in Asia-Pacific generally tends to fall between the trends appreciated in the American and European cohorts.


Subject(s)
Graves Disease , Graves Ophthalmopathy , Humans , Graves Ophthalmopathy/drug therapy , Practice Patterns, Physicians' , Iodine Radioisotopes/therapeutic use , Graves Disease/diagnosis , Graves Disease/therapy , Surveys and Questionnaires , Thyroid Hormones/therapeutic use , Antithyroid Agents/therapeutic use , Asia
3.
J Cancer Res Ther ; 19(7): 2104-2107, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-38376332

ABSTRACT

ABSTRACT: High-grade neuroendocrine carcinoma (NEC) of the tonsil is rare and has a poor prognosis. The usual presentation is a neck mass with locoregional cervical lymphadenopathy. An axillary lymphadenopathy as a primary presentation of NEC of the tonsils is uncommon and challenging to treat. Tonsil neuroendocrine tumors display aggressive behaviors associated with early recurrence and metastasis after surgical resection. Managing this condition is demanding compared to NECs of gastrointestinal origin since, to date, the management of head-and-neck neuroendocrine tumors is still not well established. We present a 49-year-old female with a rare case of NEC of the tonsil presenting primarily with axillary lymph nodes metastasis. The patient's axillary lymph node was biopsied and revealed a Grade III neuroendocrine tumor. A positron emission tomography (PET) scan was done in searching of a primary lesion and showed a highly metabolic mass of the left tonsil as well as a left axillary lymph node suggestive of metastasis. The patient has been managed with a multimodality approach, with a combination of chemotherapy regimen and surgical resection of the axillary lymph node. Subsequent PET scan evaluation showed a complete response of the primary tumor with residual left axillary lymph node metastasis. NECs of tonsil presented with axillary lymph nodes metastasis is rare and has a poor prognostic outcome. It poses a dilemma with regard to management, as surgical resection of the metastasis is not promising given the possibility of early recurrence.


Subject(s)
Carcinoma, Neuroendocrine , Lymphadenopathy , Neuroendocrine Tumors , Female , Humans , Middle Aged , Lymphatic Metastasis , Palatine Tonsil , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/therapy , Lymph Nodes
4.
Cureus ; 14(6): e25999, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35855229

ABSTRACT

Advanced thyroid carcinoma involving the upper aerodigestive tract confers a poor prognosis mainly due to airway complications. The management of thyroid carcinoma with infiltration to the aerodigestive tract has been widely discussed with no consensus regarding the best surgical technique. Complete surgical resection is the aim of the surgery. However, it has high morbidity if the postsurgical care is compromised, which will lead to airway obstruction, bleeding, infection, and anastomotic dehiscence. In our center, complete resection was achieved through cricotracheal window resection with partial closure and tracheostomy tube insertion. This procedure was chosen due to the time-sensitive nature of surgery in these patients with airway compromise and postoperative limitation of intensive care unit (ICU) bed availability. In our case series, we present six cases of papillary and follicular thyroid carcinoma complicated with intraluminal laryngotracheal infiltration and discuss its management and outcome.

5.
Health Qual Life Outcomes ; 20(1): 15, 2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35093066

ABSTRACT

BACKGROUND: Quality of life (QoL) is one of the treatment outcome measures in patients with breast cancer. In this study, we measured the QoL of women with breast cancer at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and identified the associated factors. METHODOLOGY: This cross-sectional study was conducted from October 2017 to December 2017 and involved female patients with breast cancer. The QoL scores and domains were determined using the EuroQol EQ-5D-5L, and were presented as the utility value and visual analog scores, respectively. RESULTS: We recruited a total of 173 women, aged 33-87 years. The median VA score was 80.00 (interquartile range [IQR] 70.00-90.00); the median utility value was 0.78 (interquartile range [IQR] 0.65-1.00. Women who did not take traditional medicine had a higher utility index score of 0.092 (95% CI 0.014-0.171), and women with household income of RM3000-5000 had a higher utility index score of 0.096 (95% CI 0.011-0.180). CONCLUSION: Traditional medicine consumption and household income were significantly associated with lower QoL. The pain/discomfort domain was the worst affected QoL domain and was related to traditional medicine use and household income. Addressing pain management in patients with breast cancer and the other factors contributing to lower QoL may improve the QoL of breast cancer survivors in the future.


Subject(s)
Breast Neoplasms , Quality of Life , Breast Neoplasms/therapy , Cross-Sectional Studies , Female , Humans , Referral and Consultation , Surveys and Questionnaires , Tertiary Care Centers
6.
J Voice ; 34(5): 811.e13-811.e20, 2020 Sep.
Article in English | MEDLINE | ID: mdl-30612893

ABSTRACT

OBJECTIVES: Selective laryngeal examination for patients undergoing thyroidectomy is recommended for patients with voice alterations, history of prior cervical or chest surgery, and patients with proven or suspected thyroid malignancy. The study objective is to measure the sensitivity of surgeons in detecting voice abnormalities in patients undergoing thyroidectomy, parathyroidectomy complicated with laryngeal nerve paralysis, or patients with known vocal cords palsy (VCP) due to other neck surgeries. DESIGN AND SETTING: Descriptive cross-sectional study in a tertiary center. PARTICIPANTS AND METHODS: The subjects are 274 audio files of voices of patients undergoing thyroid, parathyroid surgeries, and known VCP due to other neck surgeries. Voice assessments were done by three endocrine surgeons (A, B, and C) with 20, 12, and 4 years of surgical experience. MAIN OUTCOME MEASURES: Sensitivity and specificity of surgeon documented voice assessment in patients with underlying VCP. Subjects' acoustic analysis and Voice Handicap Index (VHI-10) were analyzed. RESULTS: Raters A, B, and C have sensitivity of 63.6%, 78.8%, and 66.7%, respectively. Inter-rater reliability shows substantial agreement (ƙ = 0.67). VHI-10 has sensitivity of 75.8% and strong correlation of 0.707 (p value <0.001) to VCP. Subjects with VCP have notably higher jitter, shimmer, and noise-to-harmonic ratio compared to normal subjects with sensitivity of 74.2%, 71.2%, and 72.7%, respectively. CONCLUSIONS: The results for surgeons documented voice assessment did not reach the desired sensitivity for a screening tool for patients with underlying VCP. Other tools such as VHI-10 and acoustic analysis may not be used as standalone tools in screening patients with underlying VCP. Routine preoperative laryngeal examination may be recommended for all patients undergoing thyroid, parathyroid, or other surgeries that places the laryngeal nerves at risk.


Subject(s)
Larynx , Surgeons , Vocal Cord Paralysis , Cross-Sectional Studies , Humans , Reproducibility of Results , Thyroidectomy/adverse effects , Vocal Cord Paralysis/diagnosis
8.
Article in English | MEDLINE | ID: mdl-31636604

ABSTRACT

Studies on excised adrenals from primary aldosteronism patients have found that somatic mutations in KCNJ5 frequently cause excess aldosterone production in the culprit aldosterone-producing adenoma (APA). KCNJ5 mutant APAs were reported to be peculiarly overrepresented among young females and in Oriental cohorts, compared to their older male, or Caucasian counterparts. These larger APAs were also reported to have similarities with the zona fasciculata (ZF) in the adrenal both from the steroid production profile and the morphology of the cell. We therefore aimed to corroborate these findings by characterizing the APAs from a multi-ethnic Malaysian cohort. The prevalence of KCNJ5 mutations was estimated through targeted DNA sequencing of KCNJ5 in 54 APAs. Confirmation of APA sample acquisition was performed by CYP11B2 immunohistochemistry (IHC) staining. The ZF steroid production profile was based on the ZF enzyme CYP17A1 IHC staining, and ZF cell morphology was based on a high cytoplasm to nucleus ratio. Seventeen (31.5%) APAs studied, harbored a KCNJ5 mutation. No female over-representation was seen in this cohort though females were found to have a higher expression of CYP11B2 than males (p = 0.009; Mann-Whitney U test). Age at adrenalectomy correlated negatively with the percentage of ZF-like cells in the APA (p = 0.01; Spearman's rho) but not with the KCNJ5 genotype. KCNJ5 mutant APAs had a high percentage of ZF-like cells (and high CYP17A1 expression) but so did the wild-type APAs. In summary, prevalence of KCNJ5 mutant APAs in this cohort was similar to other Caucasian cohorts, however, over-representation of females did not occur, which is similar to some studies in Oriental cohorts.

9.
BMJ Case Rep ; 12(8)2019 Aug 04.
Article in English | MEDLINE | ID: mdl-31383679

ABSTRACT

Acute airway obstruction in pregnancy remains a challenge to manage. Failure of appropriate and timely airway management may lead to maternal morbidity and mortality such as aspiration pneumonitis or worst hypoxaemic cardiopulmonary arrest. 1 As pregnancy may exacerbate asthma attacks, parturient presenting with wheezing or shortness of breath will commonly be treated as suffering from an asthmatic attack. 2 However, it is important to note other possible differential diagnoses. Thyroid disease is relatively common in women of childbearing age. The thyroid gland undergoes several changes during pregnancy, which may lead to altered function as well as gland enlargement and cause upper airway obstruction and symptoms similar to a bronchial asthma attack. 3 4 With that in mind, we report a case of a parturient with long-standing goitre in her second trimester who presented to our institution with acute respiratory symptoms and cardiopulmonary arrest.


Subject(s)
Airway Obstruction/diagnosis , Asthma/diagnosis , Goiter, Substernal/diagnosis , Pregnancy Complications/diagnosis , Airway Obstruction/etiology , Diagnosis, Differential , Female , Goiter, Substernal/complications , Humans , Pregnancy , Pregnancy Complications/etiology
10.
Ann Med Surg (Lond) ; 44: 57-61, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31312445

ABSTRACT

Thyroid carcinoma showing thymic-like differentiation (CASTLE) is a rare malignancy of the thyroid gland, and it accounts for 0.1-0.15% of all thyroid cancers. As the name suggests, it has a histological and immunophenotypic resemblance to thymic carcinoma. Preoperative diagnosis of CASTLE can be difficult as its clinical manifestations, and histological characteristic resembles other aggressive and advanced thyroid carcinomas. It is essential to distinguish CASTLE from other aggressive neoplasms as the former has a more favourable prognosis. Immunohistochemical staining with CD5 can help to differentiate thyroid CASTLE from other aggressive thyroid neoplasms. Due to the rarity of this disease, there is no clear definitive treatment strategy. Surgical resection of CASTLE is usually attempted initially. Nodal involvement and extrathyroidal extension are shown to be the main prognostic factors that influenced the survival of patients. Therefore, complete resection of the tumour is vital to reduce local recurrence rates and to improve the chance of long-term survival. Radiotherapy (RT) for CASTLE is an effective treatment. Curative surgery followed by adjuvant RT should be considered in cases with extrathyroidal extension and nodal metastases. With RT, shrinkage of the tumour and reduction of local recurrence rate is possible. With that in mind, we present a case of CASTLE who presented with airway compression symptoms three years after thyroid surgery. He subsequently underwent tumour debulking surgery and a tracheostomy. The patient refused adjuvant chemoradiotherapy, and during our serial follow-up, he is well and symptom-free.

11.
Article in English | MEDLINE | ID: mdl-29713312

ABSTRACT

The incidence rate of papillary thyroid carcinoma (PTC) has rapidly increased in the recent decades, and the microRNA (miRNA) is one of the potential biomarkers in this cancer. Despite good prognosis, certain features such as lymph node metastasis (LNM) and BRAF V600E mutation are associated with a poor outcome. More than 50% of PTC patients present with LNM and BRAF V600E is the most common mutation identified in this cancer. The molecular mechanisms underlying these features are yet to be elucidated. This study aims to elucidate miRNA-genes interaction networks in PTC with or without LNM and to determine the association of BRAF V600E mutation with miRNAs and genes expression profiles. Next generation sequencing was performed to characterize miRNA and gene expression profiles in 20 fresh frozen tumor and the normal adjacent tissues of PTC with LNM positive (PTC LNM-P) and PTC without LNM (PTC LNN). BRAF V600E was genotyped using Sanger sequencing. Bioinformatics integration and pathway analysis were performed to determine the regulatory networks involved. Based on network analysis, we then investigated the association between miRNA and gene biomarkers, and pathway enrichment analysis was performed to study the role of candidate biomarkers. We identified 138 and 43 significantly deregulated miRNAs (adjusted p value < 0.05; log2 fold change ≤ -1.0 or ≥1.0) in PTC LNM-P and PTC LNN compared to adjacent normal tissues, respectively. Ninety-six miRNAs had significant expression ratios of 3p-to-5p in PTC LNM-P as compared to PTC LNN. In addition, ribosomal RNA-reduced RNA sequencing analysis revealed 699 significantly deregulated genes in PTC LNM-P versus normal adjacent tissues, 1,362 genes in PTC LNN versus normal adjacent tissue, and 1,576 genes in PTC LNM-P versus PTC LNN. We provide the evidence of miRNA and gene interactions, which are involved in LNM of papillary thyroid cancer. These findings may lead to better understanding of carcinogenesis and metastasis processes. This study also complements the existing knowledge about deregulated miRNAs in papillary thyroid carcinoma development.

12.
Indian J Pathol Microbiol ; 60(3): 430-432, 2017.
Article in English | MEDLINE | ID: mdl-28937391

ABSTRACT

Metastatic disease involving the thyroid gland is uncommon. Solitary thyroid metastases from various primary sites particularly kidney, lung, and breast had been previously described. To the best of our knowledge, metastases from two topographically separate primary malignancies to the thyroid have never been documented hitherto. This is the first reported case of cancer-to-cancer metastasis involving an invasive breast carcinoma metastasized within a metastatic renal cell carcinoma in the nonneoplastic thyroid in a 58-year-old woman. Distinguishing a secondary thyroid metastases from a primary thyroid malignancy is utmost crucial as treatment differs. The possibility of tumor metastases from two separated primaries should always be considered in a tumor exhibiting malignant cell populations with two distinctive histomorphological appearances. The role of immunohistochemistry stains in equivocal cases cannot be overemphasized.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/pathology , Thyroid Neoplasms/pathology , Thyroid Neoplasms/secondary , Biomarkers, Tumor/analysis , Female , Histocytochemistry , Humans , Immunohistochemistry , Microscopy , Middle Aged
13.
PeerJ ; 4: e2119, 2016.
Article in English | MEDLINE | ID: mdl-27350898

ABSTRACT

Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion. We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.

14.
Asian Pac J Cancer Prev ; 17(1): 25-35, 2016.
Article in English | MEDLINE | ID: mdl-26838219

ABSTRACT

Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) has been shown to be associated with increased risk of locoregional recurrence, poor prognosis and decreased survival, especially in older patients. Hence, there is a need for a reliable biomarker for the prediction of LNM in this cancer. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene translation or degradation and play key roles in numerous cellular functions including cell-cycle regulation, differentiation, apoptosis, invasion and migration. Various studies have demonstrated deregulation of miRNA levels in many diseases including cancers. While a large number of miRNAs have been identified from PTCs using various means, association of miRNAs with LNM in such cases is still controversial. Furthermore, studies linking most of the identified miRNAs to the mechanism of LNM have not been well documented. The aim of this review is to update readers on the current knowledge of miRNAs in relation to LNM in PTC.


Subject(s)
Carcinoma/genetics , Carcinoma/pathology , Lymphatic Metastasis/genetics , Lymphatic Metastasis/pathology , MicroRNAs/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Animals , Biomarkers, Tumor/genetics , Carcinoma, Papillary , Humans , Lymph Nodes/pathology , Thyroid Cancer, Papillary
15.
Malays J Med Sci ; 22(4): 69-72, 2015.
Article in English | MEDLINE | ID: mdl-26715910

ABSTRACT

Papillary thyroid carcinoma (PTC) associated with familial adenomatous polyposis (FAP) is rare. It is usually associated with the cribriform-morular variant of PTC, with unusual patterns on detailed histology examination. This variant is known to have a good prognosis. Papillary thyroid carcinoma associated with FAP commonly occurs in females in their 30s and rarely in the elderly. We report a case of a 69-year-old female presenting with thyroid swelling and a history of FAP.

16.
PLoS One ; 10(1): e0117104, 2015.
Article in English | MEDLINE | ID: mdl-25629968

ABSTRACT

CHEK2 is a protein kinase that is involved in cell-cycle checkpoint control after DNA damage. Germline mutations in CHEK2 gene have been associated with increase in breast cancer risk. The aim of this study is to identify the CHEK2 gene germline mutations among high-risk breast cancer patients and its contribution to the multiethnic population in Malaysia. We screened the entire coding region of CHEK2 gene on 59 high-risk breast cancer patients who tested negative for BRCA1/2 germline mutations from UKM Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Sequence variants identified were screened further in case-control cohorts consisting of 878 unselected invasive breast cancer patients (180 Malays, 526 Chinese and 172 Indian) and 270 healthy individuals (90 Malays, 90 Chinese and 90 Indian). By screening the entire coding region of the CHEK2 gene, two missense mutations, c.480A>G (p.I160M) and c.538C>T (p.R180C) were identified in two unrelated patients (3.4%). Further screening of these missense mutations on the case-control cohorts unveiled the variant p.I160M in 2/172 (1.1%) Indian cases and 1/90 (1.1%) Indian control, variant p.R180C in 2/526 (0.38%) Chinese cases and 0/90 Chinese control, and in 2/180 (1.1%) of Malay cases and 1/90 (1.1%) of Malay control. The results of this study suggest that CHEK2 mutations are rare among high-risk breast cancer patients and may play a minor contributing role in breast carcinogenesis among Malaysian population.


Subject(s)
Breast Neoplasms/genetics , Checkpoint Kinase 2/genetics , Genetic Predisposition to Disease , Mutation, Missense , Adult , Asian People/genetics , Breast Neoplasms/ethnology , Breast Neoplasms/pathology , Case-Control Studies , Female , Humans , Malaysia , Middle Aged
17.
Int J Oncol ; 45(5): 1959-68, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25175708

ABSTRACT

There have been many DNA methylation studies on breast cancer which showed various methylation patterns involving tumour suppressor genes and oncogenes but only a few of those studies link the methylation data with gene expression. More data are required especially from the Asian region and to analyse how the epigenome data correlate with the transcriptome. DNA methylation profiling was carried out on 76 fresh frozen primary breast tumour tissues and 25 adjacent non-cancerous breast tissues using the Illumina Infinium(®) HumanMethylation27 BeadChip. Validation of methylation results was performed on 7 genes using either MS-MLPA or MS-qPCR. Gene expression profiling was done on 15 breast tumours and 5 adjacent non-cancerous breast tissues using the Affymetrix GeneChip(®) Human Gene 1.0 ST array. The overlapping genes between DNA methylation and gene expression datasets were further mapped to the KEGG database to identify the molecular pathways that linked these genes together. Supervised hierarchical cluster analysis revealed 1,389 hypermethylated CpG sites and 22 hypomethylated CpG sites in cancer compared to the normal samples. Gene expression microarray analysis using a fold-change of at least 1.5 and a false discovery rate (FDR) at p>0.05 identified 404 upregulated and 463 downregulated genes in cancer samples. Integration of both datasets identified 51 genes with hypermethylation with low expression (negative association) and 13 genes with hypermethylation with high expression (positive association). Most of the overlapping genes belong to the focal adhesion and extracellular matrix-receptor interaction that play important roles in breast carcinogenesis. The present study displayed the value of using multiple datasets in the same set of tissues and how the integrative analysis can create a list of well-focused genes as well as to show the correlation between epigenetic changes and gene expression. These gene signatures can help us understand the epigenetic regulation of gene expression and could be potential targets for therapeutic intervention in the future.


Subject(s)
Breast Neoplasms/genetics , Carcinogenesis/genetics , DNA Methylation/genetics , Epigenesis, Genetic , Aged , Breast Neoplasms/pathology , CpG Islands/genetics , Epigenomics , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/genetics , Genomics , Humans , Middle Aged , Neoplasm Staging , Promoter Regions, Genetic
18.
PLoS One ; 9(2): e89172, 2014.
Article in English | MEDLINE | ID: mdl-24586570

ABSTRACT

Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/pathology , Ki-67 Antigen/metabolism , Receptors, Estrogen/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Middle Aged , Prognosis , Receptor, ErbB-2/metabolism , Young Adult
19.
Asian J Surg ; 36(4): 150-3, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23726827

ABSTRACT

BACKGROUND: The anatomical orientation of structures in the axilla has not been well studied, although it is essential for a neat and safe dissection. The objective of this study was to determine the relations between neurovascular structures in the axilla as they were encountered during axillary lymph node dissection (ALND) for breast cancer. METHODS: This was a prospective study of 29 consecutive ALNDs accompanying either mastectomy or wide local excision. The dissections were conducted in a stepwise manner and the orientation of the structures was determined as the dissections advanced from superficial to deeper planes. RESULTS: The medial pectoral pedicle was the most superficial neurovascular structure encountered during the dissections and was curled around the lateral border of the pectoralis minor muscle in most cases. The intercostobrachial nerve lay 1-2 cm behind and below, and the axillary vein was located 2-3 cm behind and above the pedicle. The long thoracic nerve was constantly found 2-3 cm behind the intercostobrachial nerve. The thoracodorsal nerve was always accompanied by a posterior tributary of the axillary vein. CONCLUSION: Relations between neurovascular structures in the axilla are predictable. The medial pectoral pedicle, which is consistently found and superficially located, could be used as a landmark for ALND.


Subject(s)
Axilla/anatomy & histology , Lymph Node Excision/methods , Pectoralis Muscles/anatomy & histology , Adult , Female , Humans , Male , Middle Aged , Prospective Studies
20.
Asian Pac J Cancer Prev ; 14(3): 1655-9, 2013.
Article in English | MEDLINE | ID: mdl-23679251

ABSTRACT

BACKGROUND: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR). MATERIALS AND METHODS: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification. RESULTS: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR. CONCLUSION: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/pathology , Breast/metabolism , Gene Amplification , Real-Time Polymerase Chain Reaction , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , DNA/genetics , Female , Humans , Immunoenzyme Techniques , Middle Aged , Prognosis , Proto-Oncogene Mas
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