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  1. Wan Abdul Rahman WF, Fauzi MH, Jaafar H
    Asian Pac J Cancer Prev, 2014;15(19):8441-5.
    PMID: 25339043
    BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2).

    METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH).

    RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).

    CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

  2. Yaroko AA, Mohamad I, Abdul Karim AH, Wan Abdul Rahman WF
    Malays Fam Physician, 2014;9(2):61-3.
    PMID: 25883768 MyJurnal
    Thyroglossal duct cyst (TDC) is a developmental anomaly that usually appears in early childhood. The common presentation is midline swelling of the neck, which moves with both tongue protrusion and deglutition. Diagnosis is usually clinical and radiological. Fine needle aspiration cytology (FNAC) can be used as a tool for the exclusion of malignancy in adult patients. In some cases thyroid scan is done to rule out the presence or absence of the normal thyroid gland. A complete work-up is mandatory before cyst removal given that it contains only thyroid tissue. We report the case of a 32-year-old woman with only thyroid tissue in thyroglossal duct cyst.
  3. Wan Abdul Rahman WF, Mutum SS, Fauzi MH
    BMJ Case Rep, 2013;2013.
    PMID: 23878290 DOI: 10.1136/bcr-2013-010172
    Cysts of the oesophagus are unusual findings and they are classified according to the embryological site of origin. It may represent inclusion cysts, retention cysts and developmental cysts. We present a case of keratinous inclusion cyst of the lower oesophagus in a 71-year-old Malay woman who presented with dyspepsia and severe epigastric pain. An oesophago-gastro-duodenoscopy demonstrated a sliding hiatus hernia with whitish ulcer-like lesion at the lower oesophagus. Biopsy from the lesion revealed a keratinous inclusion cyst. The patient was given pantoprazole and put on regular follow-up for monitoring any other development.
  4. Mohamad Pakarul Razy NH, Wan Abdul Rahman WF, Win TT
    Asian Pac J Cancer Prev, 2019 Jan 25;20(1):277-282.
    PMID: 30678450
    Introduction: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in
    thyroid cancer. VEGF is known to have high affinity to VEGF receptors such as VEGFR-1 (Flt-1) and VEGFR-2 (KDR).
    Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and studies showed the increasing incidence of
    PTC arising in nodular hyperplasia. Targeted therapy on these growth factors and receptors are used in management
    of both differentiated and undifferentiated thyroid carcinoma. This study aims to determine the expression of VEGF
    and VEGF receptors (VEGFR) in thyroid nodular hyperplasia and PTC. Methods: A cross-sectional study based on
    paraffinized archival tissue blocks of 113 nodular hyperplasias and 67 PTC from the thyroidectomy specimens in
    the year of 2003 to 2014. The tissue sections were then stained by immunohistochemistry for VEGF, VEGFR-1 and
    VEGFR-2. The lymph node involvement and extrathyroid extension also were determined. Results: The mean age of
    PTC patients was 44.7±15.8 years and nodular hyperplasia were 42.2±13.6 years. There was a statistical difference
    of VEGFR-1 (p=0.028) and VEGFR-2 (p=0.003) expression between nodular hyperplasia and PTC. However, no
    significant difference of VEGF expression (p=0.576) between both diseases. Co-expression of VEGF and VEGFR-1
    was significant in both nodular hyperplasia (p=0.016) and PTC (p=0.03), meanwhile no relevant relationship for VEGF
    and VEGFR-2 expression (p>0.05). No significant association (p>0.05) between lymph node status and extrathyroid
    extension with age groups, gender, VEGF and VEGFR expression. Conclusions: VEGF, VEGFR-1 and VEGFR-2
    showed overexpression in both nodular hyperplasia and PTC. The expression of VEGFR-1 and VEGFR-2 are more
    significant in PTC with relevant co-expression of VEGF and VEGFR-1. Therefore, the inhibition of VEGFR offers a
    promising prospect for tumour management in thyroid carcinoma.
  5. Choo CS, Wan Abdul Rahman WF, Jaafar H, Ramli RR
    BMJ Case Rep, 2019 Mar 09;12(3).
    PMID: 30852518 DOI: 10.1136/bcr-2018-228969
    Chondrosarcoma (CS) is a malignant tumour of long and flat bone characterised by the formation of cartilage. Mesenchymal chondrosarcoma (MCS) is a rare subtype of CS that is more aggressive and may lead to erroneous diagnosis in a limited biopsy. The diagnosis is mainly based on the histopathological appearance of biphasic pattern of undifferentiated small round cells separated by islands of well-differentiated hyaline cartilage. We report a case of 13-year-old boy who initially presented with gum swelling and the biopsy result suggested a benign fibrous lesion. Following an extensive lesion shown in radiologic findings, the tumour excision was done and finally was diagnosed as an MCS of the maxilla. The patient was given postoperative chemotherapy (EURO-EWING 99 regimen), and now on regular follow-up for monitoring of local recurrence or tumour metastasis.
  6. Che Jalil NA, Rama Chandran P, Samsudin AHZ, Yahya MM, Wan Abdul Rahman WF
    Malays J Pathol, 2021 Apr;43(1):69-73.
    PMID: 33903308
    Cancer metastasis to the thyroid gland from non-thyroid sites is a rare presentation in clinical practice. The most frequent primary cancers that metastasise to the thyroid are renal cell carcinoma, followed by colorectal, lung and breast. We report a case of a 64-year-old Malay lady who presented with anterior neck swelling 4 years after an initial diagnosis of uterine leiomyosarcoma. She had undergone a hysterectomy procedure four years ago. Fine needle aspiration cytology of the thyroid mass suggested undifferentiated thyroid carcinoma. After multi-disciplinary discussion, the patient underwent thyroidectomy and the final histopathological diagnosis was metastatic leiomyosarcoma of the thyroid. The diagnosis was aided by an immunohistochemistry panel of positive myogenic markers, negative epithelial markers as well as the previous medical history of uterine leiomyosarcoma. Metastatic leiomyosarcoma of the thyroid may mimic primary undifferentiated (anaplastic) thyroid carcinoma (UTC) with a sarcomatoid pattern, medullary thyroid carcinoma (MTC) with spindle cells morphology and spindle cell tumour with thymus-like differentiation (SETTLE). Hence, a multidisciplinary approach must be practised by pathologists, surgeons and radiologists to consider metastatic lesions of the thyroid gland, especially when a previous history of cancer exists or is suspected.
  7. Jaffar NFN, Muhammad Sakri MS, Jaafar H, Wan Abdul Rahman WF, Tengku Din TADA
    Asian Pac J Cancer Prev, 2020 Oct 01;21(10):2919-2925.
    PMID: 33112549 DOI: 10.31557/APJCP.2020.21.10.2919
    OBJECTIVE: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib.

    METHODS: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis.

    RESULTS: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring.

    CONCLUSION: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.
    .

  8. Maruthamuthu T, Saniasiaya J, Mohamad I, Nadarajah S, Lazim NM, Wan Abdul Rahman WF
    Oman Med J, 2018 Jul;33(4):342-345.
    PMID: 30038735 DOI: 10.5001/omj.2018.62
    Parotid gland surgery can be challenging due to intricate relationship between the gland and facial nerve. Besides complete removal of the lesion, the main focus of surgery is centered on the facial nerve. Surgery can be technically demanding especially when the tumor is large or involves the deep lobe. We report a patient with a 30-year history of gigantic parotid mass, which initial fine-needle aspiration cytology reported as pleomorphic adenoma. The tumor, weighing 1.3 kg, was successfully resected with facial nerve preservation. Histopathological examination of the excised mass confirmed as carcinoma ex pleomorphic adenoma (CaExPA) of adenocarcinoma, not otherwise specified type. We describe the specific surgical and reconstruction techniques for successful removal of large parotid tumors with facial nerve preservation. To our knowledge, this is the heaviest CaExPA of the parotid gland in South-East Asian region.
  9. Muhammad Sakri MS, Tengku Din TADA, Jaafar H, Gopalan V, Wan Abdul Rahman WF
    Int J Immunopathol Pharmacol, 2022;36:20587384211059673.
    PMID: 35037503 DOI: 10.1177/20587384211059673
    Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.
  10. Siddig A, Tengku Din TADA, Mohd Nafi SN, Yahya MM, Sulong S, Wan Abdul Rahman WF
    Genes (Basel), 2021 03 05;12(3).
    PMID: 33807872 DOI: 10.3390/genes12030372
    Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.
  11. Mohd Fauzi NA, Ibrahim NI, Wan Abdul Rahman WF, Tuan Sharif SE, Abu Bakar MN, Ramli RR
    Ann Med Surg (Lond), 2021 Dec;72:103032.
    PMID: 34849218 DOI: 10.1016/j.amsu.2021.103032
    Introduction and importance: A solitary fibrous tumour (SFT) is a rare neoplasm that commonly arises in the pleura and can occur in other extrathoracic sites. Extrapleural SFT, particularly in the sinonasal cavity, is extremely rare. There are no definite diagnostic criteria for sinonasal SFT as it is rare. Histologic analysis with immunohistochemistry plays an important role in diagnosing SFT.

    Case presentation: We report herein a case of SFT of the sinonasal cavity, which later spread to the oral cavity in a 67-year-old male with underlying papillary thyroid carcinoma (PTC) stage IV. He complained of recurrent epistaxis from a mass in his left nasal cavity for two weeks. The mass grew bigger, and spread to the oral cavity, causing dysphagia and upper airway obstruction. Tracheostomy was done under local anaesthesia and a biopsy of the mass was taken to rule out metastasis from the PTC. However, histopathological examination revealed a mesenchymal tumour of fibroblastic type, consistent with an SFT. He was planned for surgical resection of the tumour. However, he refused the operation and was lost to follow-up.

    Clinical discussion: We describe the clinical presentation of this rare tumour of the sinonasal and oral cavity, including upper airway obstruction, and the importance of immunohistochemical markers such as CD34 and BCL-2 in diagnosing SFT. Complete resection of the tumour is the definitive treatment for SFT.

    Conclusion: SFT of the sinonasal and oral cavity is extremely rare. Upper airway obstruction may occur due to the location of the tumour in the airway region. Immunohistochemistry is crucial to distinguish this tumour from other mesenchymal tumours.

  12. Hanis TM, Ruhaiyem NIR, Arifin WN, Haron J, Wan Abdul Rahman WF, Abdullah R, et al.
    Diagnostics (Basel), 2022 Nov 16;12(11).
    PMID: 36428886 DOI: 10.3390/diagnostics12112826
    This study aims to determine the feasibility of machine learning (ML) and patient registration record to be utilised to develop an over-the-counter (OTC) screening model for breast cancer risk estimation. Data were retrospectively collected from women who came to the Hospital Universiti Sains Malaysia, Malaysia for breast-related problems. Eight ML models were used: k-nearest neighbour (kNN), elastic-net logistic regression, multivariate adaptive regression splines, artificial neural network, partial least square, random forest, support vector machine (SVM), and extreme gradient boosting. Features utilised for the development of the screening models were limited to information in the patient registration form. The final model was evaluated in terms of performance across a mammographic density. Additionally, the feature importance of the final model was assessed using the model agnostic approach. kNN had the highest Youden J index, precision, and PR-AUC, while SVM had the highest F2 score. The kNN model was selected as the final model. The model had a balanced performance in terms of sensitivity, specificity, and PR-AUC across the mammographic density groups. The most important feature was the age at examination. In conclusion, this study showed that ML and patient registration information are feasible to be used as the OTC screening model for breast cancer.
  13. Wan Juhari WK, Wan Abdul Rahman WF, Mohd Sidek AS, Abu Hassan MR, Ahmad Amin Noordin KB, Zakaria AD, et al.
    Asian Pac J Cancer Prev, 2015;16(9):3767-71.
    PMID: 25987035
    BACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry.

    MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.

    RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.

    CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

  14. Yusoff MSB, Hadie SNH, Mohamad I, Draman N, Muhd Al-Aarifin I, Wan Abdul Rahman WF, et al.
    Malays J Med Sci, 2020 May;27(3):137-142.
    PMID: 32684814 MyJurnal DOI: 10.21315/mjms2020.27.3.14
    During the first phase of the Movement Control Order, many medical lecturers had difficulty adapting to the online teaching and learning methods that were made compulsory by the institutional directives. Some of these lecturers are clinicians who need to juggle between clinical work and teaching, and consider a two-week adaptation during this period to be not enough. Furthermore, converting traditional face-to-face learning to online formats for undergraduate and postgraduate clinical programmes would reduce the learning outcomes, especially those related to clinical applications and the acquisition of new skills. This editorial discusses the impact that movement restrictions have had on medical teaching and learning, the alternatives and challenges and the way forward.
  15. Dass SA, Tan KL, Selva Rajan R, Mokhtar NF, Mohd Adzmi ER, Wan Abdul Rahman WF, et al.
    Medicina (Kaunas), 2021 Jan 12;57(1).
    PMID: 33445543 DOI: 10.3390/medicina57010062
    Triple-negative breast cancer (TNBC) is an aggressive breast type of cancer with no expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). It is a highly metastasized, heterogeneous disease that accounts for 10-15% of total breast cancer cases with a poor prognosis and high relapse rate within five years after treatment compared to non-TNBC cases. The diagnostic and subtyping of TNBC tumors are essential to determine the treatment alternatives and establish personalized, targeted medications for every TNBC individual. Currently, TNBC is diagnosed via a two-step procedure of imaging and immunohistochemistry (IHC), which are operator-dependent and potentially time-consuming. Therefore, there is a crucial need for the development of rapid and advanced technologies to enhance the diagnostic efficiency of TNBC. This review discusses the overview of breast cancer with emphasis on TNBC subtypes and the current diagnostic approaches of TNBC along with its challenges. Most importantly, we have presented several promising strategies that can be utilized as future TNBC diagnostic modalities and simultaneously enhance the efficacy of TNBC diagnostic.
  16. Siddig A, Wan Abdul Rahman WF, Mohd Nafi SN, Sulong S, Yahya MM, Al-Astani Tengku Din TAD, et al.
    Biomedicines, 2023 Jan 12;11(1).
    PMID: 36672708 DOI: 10.3390/biomedicines11010200
    Background: Breast cancer developed at a young age (≤45 years) is hypothesized to have unique biology; however, findings in this field are controversial. Methods: We compared the whole transcriptomic profile of young vs. old-age breast cancer using DNA microarray. RNA was extracted from 13 fresh estrogen receptor (ER)-positive primary breast cancer tissues of untreated patients (7 = young age ≤45 years and 6 = old age ≥55 years). In silico validation for the differentially expressed genes (DEGs) by young-age patients was conducted using The Cancer Genome Atlas (TCGA) database. Next, we analyzed the protein expression encoded by two of the significantly down-regulated genes by young-age patients, Glycine N-acyltransferase-like 1 (GLYATL-1) and Ran-binding protein 3 like (RANBP3L), using immunohistochemical analysis in an independent cohort of 56 and 74 ER-positive pre-therapeutic primary breast cancer tissues, respectively. Results: 12 genes were significantly differentially expressed by young-age breast cancers (fold change >2 or <2- with FDR p-value < 0.05). TCGA data confirmed the differential expression of six genes. Protein expression analysis of GLYATL-1 and RANBP3L did not show heterogeneous expression between young and old-age breast cancer tissues. Loss of expression of GLYATL-1 was significantly (p-value 0.005) associated with positive lymph node status. Higher expression of RANBP3L was significantly associated with breast cancers with lower histopathological grades (p-value 0.038). Conclusions: At the transcriptomic level, breast cancer developed in young and old age patients seems homogenous. The variation in the transcriptomic profiles can be attributed to the other clinicopathological characteristics rather than the age of the patient.
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