1.MGMT and SPOCK2 Promoter Methylation in Diffuse Large B-Cell Lymphoma: A Study in Two Tertiary Health Centres in the East Coast of Malaysia
Norafiza Zainuddin ; Lailatul Jalilah Mohd Ridah ; Aqilah Nabihah Omar ; Norlelawati A. Talib ; Naznin Muhammad ; Faezahtul Arbaeyah Hussain
Malaysian Journal of Health Sciences 2017;15(2):77-82
MGMT (O6
-Methylguanine-DNA Methyltransferase) suppresses tumor development by removing alkyl adduct, while
SPOCK2 (SPARC/Osteonectin CWCV and Kazal-like domains proteoglycan) abolishes the inhibition of membrane-type
matrix metalloproteinases (MT-MMP) which leads to angiogenesis. Hence, MGMT methylation may initiate malignant cells
transformation. In contrast, SPOCK2 methylation is hypothesized not to be a common event in diffuse large B-cell lymphoma
(DLBCL). In this study, we examined the methylation status of MGMT and SPOCK2 in DLBCL as in Malaysia the information
is extremely lacking. A total of 88 formalin-fixed paraffin-embedded tissue of patients diagnosed with DLBCL from the
year 2006 to 2013 were retrieved from Hospital Universiti Sains Malaysia, Kelantan and Hospital Tengku Ampuan Afzan,
Pahang. Methylation-specific polymerase chain reaction (MSP) was used to examine the methylation status of both genes.
Interestingly, methylation of MGMT was detected in all the 88 DLBCL samples, whereas SPOCK2 was found to be methylated
in 83 of 88 (94.3%) DLBCL cases. Our study showed a remarkably high percentage of promoter methylation of both
MGMT and SPOCK2 genes. Our finding also negates initial expectation that SPOCK2 methylation would be an uncommon
event in the majority of DLBCL cases. This study has shown a very high percentage of promoter methylation of MGMT and
SPOCK2 in the DLBCL cases studied by MSP, using archival lymphoma tissues. Nonetheless, additional research is needed
to quantitatively evaluate MGMT and SPOCK2 methylation, and to analyse gene expression and/or protein expression in
order to further understand the role of MGMT and SPOCK2 methylation in the pathogenesis of DLBCL.
2.Anti-HER2 Antibodies In Combination With Chemotherapy Or Chemotherapy-Free Regimens Targeting Her2-Positive Breast Cancer: A Systematic Review
Siti Muhamad Nur Husna ; Faezahtul Arbaeyah Hussain ; Maya Mazuwin Yahya ; Anne Dyhl-Polk ; Kah Keng Wong
Malaysian Journal of Public Health Medicine 2020;20(2):285-306
Breast cancer is the leading cause of cancer-related death in female worldwide. Human epidermal growth factor receptor 2 (HER2) amplification is observed in approximately 20% of breast cancer cases and is associated with poor clinical outcomes. Dual HER2 blockade without chemotherapy represents an attractive therapeutic approach, and it remains unresolved if anti-HER2 therapeutic antibodies are sufficient to replace chemotherapy regimens. In this review, we discuss the approved therapeutic monoclonal antibodies (pertuzumab and trastuzumab) and antibody-drug conjugate (trastuzumab emtansine or T-DM1) for the treatment of HER2-positive breast cancer patients. In summary, phase II and III clinical trials have demonstrated that dual HER2 blockade (pertuzumab and trastuzumab) plus chemotherapy regimens confer better efficacy compared with dual HER2 blockade alone, or anti-HER2 antibody monotherapy, in HER2-positive breast cancer patients. Dual HER2 blockade (pertuzumab and trastuzumab) combined with chemotherapies (5-fluorouracil, epirubicin, cyclophosphamide and docetaxel) yield superior response. Moreover, dual HER2 blockade (T-DM1 and pertuzumab) in combination with docetaxel represents a promising treatment regimen containing T-DM1. Ongoing clinical trials are assessing the optimal chemotherapy of choice with anti-HER2 antibodies combinations. In conclusion, improved outcomes are attributable to selection for the optimal chemotherapy regimen in combination with anti-HER2 antibodies instead of replacing chemotherapy altogether with the current line of anti-HER2 therapeutic antibodies.
3.Classifying DLBCL according cell of origin using Hans algorithm and its association with clinicopathological parameters: A single centre experience
Wan Nor Najmiyah Wan Abdul Wahab ; Azlan Husin ; Faezahtul Arbaeyah Hussain
The Medical Journal of Malaysia 2020;75(2):98-102
Introduction: In recent years, "double hit" and "double
protein" involving gene rearrangement and protein
expression of c-MYC and BCL2 and/or BCL6 are the most
used terms to describe poor prognostic factors in diffuse
large B-cell lymphoma (DLBCL). This study was to
determine the frequency of double or triple protein
expression by using immunohistochemistry (IHC) and
comparing the result with clinicopathological features and
cell of origin (COO) classification.
Methods: We conducted a cross-sectional study by using 29
archived formalin-fixed paraffin embedded tissue blocks of
DLBCL. All the samples were evaluated for the subgrouping
of COO DLBCL was determined by expression of CD10,
BCL6 and MUM1 based on Hans classification. In addition,
expressions of c-MYC, BCL2 and BCL6 were detected by
IHC.
Results: Among the 29 cases, MYC, BCL2 and BCL6 proteins
were detected in 72.4%, 62.1% and 62.1% of patients,
respectively. Concurrent expression (c-MYC positive/BCL2
positive and/or BCL6 positive) was present in 58.6% of
patients. 34.5% were categorised as germinal centre like
(GCB) subgroup and 65.5% were categorised as nongerminal centre like (non-GCB) subgroup. Among the
clinicopathological features, the double/triple protein
expression lymphoma was significantly associated with
elevated LDH level (p=0.018), IPI score (p=0.003), Ann Arbor
stage (p=0.011) and complete response rate (p=0.011).
Conclusion: Double/triple protein lymphoma was strongly
associated more adverse clinical risk factors. Thus,
analyses of MYC, BCL2 and BCL6 expression by IHC
represents a rapid and inexpensive approach to risk-stratify
patients with DLBCL at diagnosis.
4.Kimura Disease as a Rare Cause of Proptosis: A Case Report
V Sha Kri Eh Dam ; Irfan Mohamad ; Evelyn Li Min Tai ; Adil Hussein ; Khairil Amir Sayuti ; Fatihatul Munirah Amiruddin ; Faezahtul Arbaeyah Hussain
Archives of Orofacial Sciences 2021;16(2):259-265
ABSTRACT
Kimura disease (KD) is a rare chronic inflammatory disorder of unknown aetiology that primarily affects
the head and neck region with lymph node involvement. Young to middle-aged adult Asian males are
predominantly affected. The most common presentation is painless subcutaneous swelling in the head
and neck region, while proptosis or orbital involvement is very rarely reported. KD shares some features
with other inflammatory and neoplastic disorders, including lymphoma; thus, investigations to confirm
the diagnosis should not be delayed. Systemic corticosteroids are commonly used to treat KD and show
an excellent response; however, the optimal treatment is still uncertain, and KD has a high recurrence
rate. We describe the case of a patient with KD who presented with proptosis and post-auricular
swelling, which responded well to oral prednisolone treatment.
Kimura Disease
;
Exophthalmos
5.Phaehyphomycosis or Eumycetoma: A Case Report of a Diagnostic Dilemma
Md Salim Siti Norfairuz ; Wan Ismail Wan Faisham ; Amiruddin Fatihatul Munirah ; Hussain Faezahtul Arbaeyah ; Abdullah Rosmaniza ; Abdul Rahman Zaidah
Malaysian Journal of Medicine and Health Sciences 2024;20(No.1):392-394
We reported a case of recurrent subcutaneous swelling on the left foot of a diabetic patient. Two different organisms,
Cladosporium spp. and Phaeoacremonium krajdenii were isolated, both of which are associated with phaeohyphomycosis and eumycetoma. The cure was achieved through surgical excision of the lesion and a course of antifungal
therapy. The diagnosis was uncertain since clinical manifestations and laboratory results were insufficient to distinguish the two diseases.