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Fulltext The Value of H3K27me3 Immunohistochemistry in Differentiating Malignant Peripheral Nerve Sheath Tumour with Its Histologic Mimickers

Mustapar N, Zawawi MSF, Tuan Sharif SE

Asian Pac J Cancer Prev, 2020 Mar 01;21(3):699-705.
PMID: 32212796 DOI: 10.31557/APJCP.2020.21.3.699

BACKGROUND: Diagnosis of malignant peripheral nerve sheath tumor (MPNST) is rather challenging due to its divergent morphologic heterogeneity and lack of specific ancillary test. The emergence of H3K27 trimethylation (H3K27me3) as a new immunohistochemistry (IHC) marker for MPNST have recently available to assist pathologists in differentiating MPNST from other histologic mimics. We aim to study the expression pattern of H3K27me3 in MPNST and its histologic mimickers and their association with the clinicopathological data.
METHODOLOGY: A total of 59 benign and malignant spindle cell tumours (18 MPNST and 41 of its histologic mimickers which included 10 schwannoma, 13 neurofibroma, 4 synovial sarcoma, 3 fibrosarcoma, 2 gastrointestinal stromal tumour (GIST), 4 leiomyosarcoma, 1 spindle cell liposarcoma, 1 solitary fibrous tumour, 2 low grade fibromyxoid sarcoma and 1 unclassified spindle cell sarcoma), diagnosed from January 1998 to April 2018 in Hospital Universiti Sains Malaysia (HUSM) were tested for H3K27me3 by IHC. The MPNST histological grade was assessed based on the French Fe'de' ration Nationale des Centres de LutteContre le Cancer (FNCLCC) for 3 tiers system (low grade, intermediate grade and high grade). The clinicopathological data were retrieved from the patients' record.
RESULTS: A total of 61.1% (11/18 MPNST) showed loss of H3K27me3 expression which is statistically significant as compared to its histologic mimics (p<0.001). Similar findings (p=0.026) were also observed in high grade MPNST (81.8%), intermediate grade MPNST (100%) and 0% in low grade MPNST.
CONCLUSION: H3K27me3, combined with other panel of markers, is useful in MPNST diagnosis to differentiate it from the histological mimickers.
Submuscular Plate Stabilisation After Lengthening: Standard and Modified Techniques

Munajat I, Sulaiman AR, Mohd EF, Zawawi M

Malays Orthop J, 2020 Mar;14(1):49-54.
PMID: 32296482 DOI: 10.5704/MOJ.2003.008

Introduction: Submuscular plating after lengthening shortened the period of external fixation in distraction osteogenesis of the femur. In the femur, where monolateral or ring fixators had been used for the distraction, plates, could be inserted laterally, anteriorly or medially. Specific technical modification of the plate insertion, however, would be necessary to accommodate the femoral varus angular correction created at the end of the distraction, in the pelvic support osteotomy lengthening.
Material and Methods: We reviewed a series of eight cases with standard and modified techniques of plating after lengthening. The amount of lengthening, the period of distraction, the external fixator index and the associated complications were assessed.
Results: The mean lengthening was 5cm, with a range of 3cm to 9cm. The external fixation index, the period of external fixators in days in relation to the length of distraction in cm, was between 18 days/cm to 58 days/cm. One patient with quadriceps contracture, underwent quadriceplasty to improve knee flexion. Three patients with transient knee stiffness had resolution with aggressive physiotherapy. One patient with transient hypoesthesia recovered spontaneously. None of the patients developed joint subluxation, deep infection, re-fracture or implant failures.
Conclusion: Standard and modified techniques of plating after lengthening were safe and required only a short period of external fixation. The modified technique offered an easier way of plate insertion in a deformed bone.
Fulltext Evaluation of the Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) Expression in Osteosarcoma and Its Association with the Clinicopathological Data

Chua HH, Tuan Sharif SE, Wan Ismail WFN, Zawawi MSF, Abdullah S

Asian Pac J Cancer Prev, 2021 Mar 01;22(3):741-747.
PMID: 33773537 DOI: 10.31557/APJCP.2021.22.3.741

BACKGROUND: The receptor activator of nuclear factor kappa B ligand (RANKL) is one of the key regulators of bone remodelling in bone oncology, including osteosarcoma. We assessed RANKL immunohistochemical expression in osteosarcoma, its association, and disease-free survival with the patients' clinicopathological characteristics.
METHODS: One hundred osteosarcoma cases from 2003 to 2018 in Hospital Universiti Sains Malaysia were retrieved. The tissue samples were stained for RANKL, and the association with the clinicopathological characteristics was evaluated. Staining was interpreted in a semiquantitative scoring system and classified into negative and positive expressions. Results: Eighty-two cases had a positive expression of RANKL in which 56 and 26 patients were classified as low expression and high expression, respectively. The positive expression of RANKL did not show a significant association with clinicopathological characteristics. However, Kaplan Meier survival analysis showed a significant improvement in the disease-free survival patients who underwent limb salvage surgery (LSS) than amputated patients (p-value 0.002), whereas poorer survival was observed among conventional osteosarcomas compared to non-conventional osteosarcoma (p-value 0.01).
CONCLUSION: Limb salvage surgery had proven to improve osteosarcoma patients' survival compared to amputation, which could improve overall quality of life in osteosarcoma patients. However, our data did not show a significant association between positive RANKL immunohistochemistry with any of the clinicopathological characteristics and patients' final survival. Further studies may be acquired to understand the suitability of using RANKL immunohistochemistry as prognostication in the management of osteosarcoma patients.
Fulltext Enhancement of Scaffold In Vivo Biodegradability for Bone Regeneration Using P28 Peptide Formulations

Azaman FA, Brennan Fournet ME, Sheikh Ab Hamid S, Zawawi MSF, da Silva Junior VA, Devine DM

Pharmaceuticals (Basel), 2023 Jun 13;16(6).
PMID: 37375823 DOI: 10.3390/ph16060876

The field of bone tissue engineering has shown a great variety of bone graft substitute materials under development to date, with the aim to reconstruct new bone tissue while maintaining characteristics close to the native bone. Currently, insufficient scaffold degradation remains the critical limitation for the success of tailoring the bone formation turnover rate. This study examines novel scaffold formulations to improve the degradation rate in vivo, utilising chitosan (CS), hydroxyapatite (HAp) and fluorapatite (FAp) at different ratios. Previously, the P28 peptide was reported to present similar, if not better performance in new bone production to its native protein, bone morphogenetic protein-2 (BMP-2), in promoting osteogenesis in vivo. Therefore, various P28 concentrations were incorporated into the CS/HAp/FAp scaffolds for implantation in vivo. H&E staining shows minimal scaffold traces in most of the defects induced after eight weeks, showing the enhanced biodegradability of the scaffolds in vivo. The HE stain highlighted the thickened periosteum indicating a new bone formation in the scaffolds, where CS/HAp/FAp/P28 75 µg and CS/HAp/FAp/P28 150 µg showed the cortical and trabecular thickening. CS/HAp/FAp 1:1 P28 150 µg scaffolds showed a higher intensity of calcein green label with the absence of xylenol orange label, which indicates that mineralisation and remodelling was not ongoing four days prior to sacrifice. Conversely, double labelling was observed in the CS/HAp/FAp 1:1 P28 25 µg and CS/HAp/FAp/P28 75 µg, which indicates continued mineralisation at days ten and four prior to sacrifice. Based on the HE and fluorochrome label, CS/HAp/FAp 1:1 with P28 peptides presented a consistent positive osteoinduction following the implantation in the femoral condyle defects. These results show the ability of this tailored formulation to improve the scaffold degradation for bone regeneration and present a cost-effective alternative to BMP-2.