Higher peripheral blood mitochondrial DNA copy number and relative telomere length in under 48 years Indonesian breast cancer patients.

OBJECTIVE: Breast cancer is the leading cause of cancer incidence and mortality among Indonesian women. A comprehensive investigation is required to enhance the early detection of this disease. Mitochondrial DNA copy number (mtDNA-CN) and relative telomere length (RTL) have been proposed as potential biomarkers for several cancer risks, as they are linked through oxidative stress mechanisms. We conducted a case-control study to examine peripheral blood mtDNA-CN and RTL patterns in Indonesian breast cancer patients (n = 175) and healthy individuals (n = 181). The relative ratios of mtDNA-CN and RTL were determined using quantitative real-time PCR (qPCR). RESULTS: Median values of mtDNA-CN and RTL were 1.62 and 0.70 in healthy subjects and 1.79 and 0.73 in breast cancer patients, respectively. We found a positive association between peripheral blood mtDNA-CN and RTL (p < 0.001). In under 48 years old breast cancer patients, higher peripheral blood mtDNA-CN (mtDNA-CN ≥ 1.73 (median), p = 0.009) and RTL (continuous variable, p = 0.010) were observed, compared to the corresponding healthy subjects. We also found a significantly higher 'High-High' pattern of mtDNA-CN and RTL in breast cancer patients under 48 years old (p = 0.011). Our findings suggest that peripheral blood mtDNA-CN and RTL could serve as additional minimally invasive biomarkers for breast cancer risk evaluation.

The role of HMGCR expression in combination therapy of simvastatin and FAC treated locally advanced breast cancer patients.

OBJECTIVE: Several studies have shown the role of statin added to the patient's chemotherapy regimen and the role of Hydroxymethylglutaryl-CoA Reductase (HMGCR) expression in predicting breast cancer patient outcomes. In our previous study, adding statins improved clinical and pathological responses in LABC patients. Furthermore, we planned to study statin's role as a combination to neoadjuvant chemotherapy (NAC) in treating locally advanced breast cancers on the basis of HMGCR expression. Moreover, we aimed to study the association between the patients' clinicopathological characteristics and HMGCR expression. METHODS: This study is a randomized, double-blinded, placebo-controlled trial in two health centers in Indonesia. Each patient enrolled with written informed consent and then randomized to receive either simvastatin 40 mg/day or a placebo, combined with the fluorouracil, adriamycin, and cyclophosphamide (FAC) NAC. RESULTS: HMGCR was associated with low staging and normal serum cholesterol in the high Ki67 level group (p = 0.042 and p = 0.021, respectively). The pre-and post-chemotherapy tumor sizes are significantly correlated in two groups (HMGCR negative expression, p = 0.000 and HMGCR moderate expression, p = 0.001) with a more considerable average decrease in tumor size compared to HMGCR strong expression group. CONCLUSION: Statin therapy might work better in HMGCR-negative or low-expression tumors, although HGMCR expression is associated with better clinical parameters in our study.

Antibacterial activity of medicinal plants in Indonesia on Streptococcus pneumoniae.

Streptococcus pneumoniae is a human pathogenic bacterium able to cause invasive pneumococcal diseases. Some studies have reported medicinal plants having antibacterial activity against pathogenic bacteria. However, antibacterial studies of medicinal plants against S. pneumoniae remains limited. Therefore, this study aims to describe the antibacterial activity of medicinal plants in Indonesia against S. pneumoniae. Medicinal plants were extracted by maceration with n-hexane, ethanol, ethyl acetate and water. Antibacterial activity was defined by inhibition zone and minimum inhibitory concentration (MIC). Bactericidal activity was measured by culture and time-killing measurement. Methods used to describe the mechanism of action of the strongest extract were done by absorbance at 595 nm, broth culture combined with 1% crystal violet, qRT-PCR targeting lytA, peZT and peZA, and transmission electron microscope to measure bacterial lysis, antibiofilm, LytA and peZAT gene expression, and ultrastructure changes respectively. Among 13 medicinal plants, L. inermis Linn. ethyl acetate extract showed the strongest antibacterial activity against S. pneumoniae with an MIC value of 0,16 mg/ml. Bactericidal activity was observed at 0,16 mg/ml for 1 hour incubation. Lawsonia inermis extract showed some mechanism of actions including bacterial lysis, antibiofilm, and ultrastructure changes such as cell wall disruption, decreasing cell membrane integrity and morphological disorder. Increasing of lytA and decreasing of peZA and peZT expression were also observed after incubation with the extract. In addition, liquid chromatography mass spectrophotometer showed phenolic compounds as the commonest compound in L. inermis ethyl acetate extract. This study describes the strong antibacterial activity of L. inermis with various mechanism of action including ultrastructure changes.

Circadian as a prognostic factor for radiation responses in patients with cervical cancer: A nested case­control study.

The radiation response of cervical cancer is thought to be enhanced by the levels of melatonin due to its roles in the circadian cycle and cancer growth. In the present study, the roles of circadian rhythms and melatonin levels as prognostic factors for predicting the radiation response in patients with cervical cancer were examined. In this nested case­control study, patients with good and poor responses to radiotherapy were assessed in terms of the time­of­day radiation treatment was administered and further influencing factors. The radiation time was determined, as the subjects were either irradiated in the morning (06.00­10.00 am) or afternoon (04.00­06.00 pm). Data on tumour size and other biological parameters were collected and analysed by binary logistic regression. Among the 56 patients examined, most subjects had good radiation responses. Most patients were <50 years old with an initial body weight of >50 kg, no pain prior to radiation, low erythrocyte sedimentation rates, normal intravenous urography results, moderate or good differentiation on pathology and histo­pathologically non­keratinised cells. According to the multivariate analysis, the irradiation time as a surrogate of the circadian cycle (morning vs. afternoon), the initial haemoglobin (Hb) level and the clinical tumour size were significant predictors of the radiation response. The circadian cycle, tumour size and Hb levels may affect the radiation response in patients with cervical cancer. In addition, the morning group had better 5­year overall survival, but it was not significant, possibly due to the small cohort size. Further research is required to identify more relevant prognostic factors using different radiotherapy techniques [National Clinical Trial (NCT) no. NCT05511740, registration date, 08/20/2022].

Two young patients with extranodal natural killer/T-cell non-Hodgkin lymphoma, nasal-type (ENKTL-NT) masquerading inflammatory processes: A case series.

Extranodal natural-killer/T-cell lymphoma (ENKTL) is a rare type of non-Hodgkin lymphoma. However, it is common in Asia and South America. ENKTL, nasal type (ENKTL-NT), predominantly presents initial unspecific clinical manifestations involving the nasal cavity and its adjacent structures. We present two cases to increase the awareness of the ENKTL-NT cases masquerading inflammatory processes. Although the main clinical feature is a rapidly progressive facial destruction, none of these patients experienced the mentioned complaint. Its various manifestations frequently lead to misdiagnosis and delayed treatment, particularly in those with marked ocular, not nasal symptoms. Our patients were previously diagnosed with inflammatory conditions, namely sinusitis, idiopathic orbital inflammation, dacryocystitis, and orbital cellulitis. The combined approach of chemotherapy and radiotherapy has been proposed as the treatment of choice. Both cases showed young adults treated with combined therapy, yet showing poor outcomes. Clinicians should be aware of its existence and have to consider ENKTL-NT as one of the differential diagnoses in sinonasal or orbital inflammatory cases with unusually rapid progression or unresponsive to treatment.

The Association Between Triglyceride-Glucose Index as a Marker of Insulin Resistance and the Risk of Breast Cancer.

Background: This study aims to evaluate the association and dose-response between triglyceride-glucose (TyG) index and breast cancer. Method: This is a multicenter case-control study conducted in six public referral hospitals in Indonesia. Cases are individuals aged 19 years or above who were diagnosed with breast cancer within 1 year of diagnosis, based on histopathology and immunohistochemistry. Controls were recruited from corresponding hospitals. TyG index was determined by the formula: ln (fasting TG [mg/dl] × fasting glucose [mg/dl]). Results: There were 212 participants in the breast cancer group and 212 participants in the control group. TyG index was higher in patients with breast cancer (median 8.65 [7.38, 10.9] vs. 8.30 [7.09, 10.84], p < 0.001). When compared with TyG quartile of Q1, Q4 was associated with an OR of 2.42 (1.77, 3.31), p < 0.001, Q3 was associated with an OR of 1.53 (1.21, 1.93), p < 0.001, Q2 was associated with an OR of 1.39 (1.12, 1.73), p = 0.002 for the risk of breast cancer. The dose-response relationship was nonlinear (p < 0.001). On univariate analysis, smoking (OR 2.15 [1.44, 3.22], p < 0.001), use of contraception (1.73 [1.15, 2.60], p = 0.008), alcohol consumption (OR 2.04 [0.96, 4.35], p = 0.064), and TyG Index >8.87 (OR 3.08 [1.93, 4.93], p < 0.001) were associated with risk of breast cancer. Independently associated with increased risk of breast cancer included smoking (OR 1.93 [1.23, 3.01], p = 0.004), use of contraception (OR 1.59 [1.02, 2.48], p = 0.039), and TyG Index >8.87 (OR 2.93 [1.72, 4.98], p < 0.001). Conclusion: TyG index was associated with breast cancer in a nonlinear dose-response fashion.

Neuroprotective Effects of Citicoline on Methanol-Intoxicated Retina Model in Rats.

Purpose: This study aims to evaluate the effect of citicoline administration in suppressing retinal damage due to methanol intoxication. This study hypothesizes that citicoline will minimize the loss of retinal ganglion cells (RGCs), minimize disruption of photoreceptors, suppress ganglion layer edema, increase expression of bcl-2 as the antiapoptotic protein, and decrease expression of caspase-3 as the proapoptotic protein. Methods: Fifteen Sprague-Dawley rats were divided into 5 groups, including the control group (A); methanol groups, observed on day 3 (B1) and day 7 (B2); and methanol+citicoline groups, observed on day 3 (C1) and day 7 (C2). Rats in groups B and C were placed in an inhalation chamber filled with N2O:O2 during the experiment, then methanol was administered orally. Citicoline, 1 g/kg every 24 h, was orally administered for group C. Enucleation was performed and retinas of rats were prepared for histology and immunohistochemistry examination to evaluate photoreceptor morphology and RGC density, as well as bcl-2 and caspase-3 expression. Results: RGC density of citicoline-treated intoxicated rats was higher than no-citicoline methanol-intoxicated rats on both day 3 (P < 0.001) and day 7 (P < 0.001). The ganglion layer thickness of citicoline-treated intoxicated rats was thinner than no-citicoline intoxicated rats, which means citicoline-treated rats had milder ganglion layer edema. Citicoline-treated rats showed higher bcl-2 and lower caspase-3 expression than no-citicoline rats. No differences were found in photoreceptor findings among groups. Conclusions: This study demonstrated citicoline's potential benefits for management of ocular methanol intoxication. However, more preclinical and clinical trials are needed to obtain a preferred dosage and timing of citicoline administration.

Comparison between PRP and PRFM on FTSG healing profile: Macroscopic, microscopic and ELISA evaluation.

BACKGROUND: Studies had shown the benefit of PRFM and PRP in wound healing but their use in skin graft healing was rarely studied. This study aims to compare the use of PRP and PRFM in accelerating wound healing process of skin full-thickness skin graft (FTSG). MATERIALS AND METHODS: Five pigs were used to look at the wound healing effect of PRP and PRFM usage prior to FTSG implantation. Subsequent punch biopsies were then conducted on the 1st, 3rd, 7th, 14th, and 30th day to obtain samples for macroscopic (skin color), extracellular matrix (collagen), microscopic (PMN, macrophage, and fibroblast), and ELISA (TGFß1 and PDGF) analysis to determine the level of wound healing activity. ImageJ software was used to photograph for macroscopic and extracellular matrix analysis. RESULTS: Macroscopic, extracellular matrix, and ELISA evaluation show no significant difference in FTSG survival rates for all treatment groups. Microscopic examination showed an increase in PMN, macrophage, and fibroblast levels with PRFM application showing higher increases in all observed microscopic variables compared to PRP and control. CONCLUSION: This study observed that both PRFM and PRP as autologous platelet preparation accelerate wound healing in FTSG, with PRFM being superior due to the higher number of PMN, macrophage, and fibroblast.

Bone Growth Capacity of Human Umbilical Cord Mesenchymal Stem Cells and BMP-2 Seeded Into Hydroxyapatite/Chitosan/Gelatin Scaffold in Alveolar Cleft Defects: An Experimental Study in Goat.

OBJECTIVE: To evaluate bone regeneration in alveolar defects treated with human umbilical cord-derived mesenchymal stem cells (hUCMSCs), hydroxyapatite/chitosan/gelatin (HA/CS/Gel) scaffold, and bone morphogenic protein-2 (BMP-2) in Capra hircus models. DESIGN: Randomized posttest-only control group design. SETTING: Animal Hospital at Bogor Agricultural Institute. PARTICIPANTS: Healthy and equally treated 24 female Capra hircus/goats. INTERVENTION: Animals were randomly assigned to 3 experimental group design (iliac crest alveolar bone graft/ICABG [control], HA/Cs/Gel+BMP-2 [Novosys], and HA/Cs/Gel+BMP-2+UCMSCs). Graft materials were implanted in surgically made alveolar defects. MAIN OUTCOME MEASURES: Postoperative functional score and operating time were assessed. New bone growth, bone density, inflammatory cells recruitment, and neoangiogenesis were evaluated based on radiological and histological approach at 2 time points, week 4 and 12. Statistical analysis was done between treatment groups. RESULTS: Operating time was 34% faster and functional score 94.5% more superior in HA/Cs/Gel+BMP-2+hUCMSC group. Bone growth capacity in HA/Cs/Gel+BMP-2+UCMSCs mimicked ICABG, but ICABG showed possibility of bone loss between week 4 and 12. The HA/Cs/Gel+BMP-2+UCMSCs showed early bone repopulation and unseen inflammatory cells and angiogenesis on week 12. DISCUSSION AND CONCLUSION: The HA/Cs/Gel+BMP-2+hUCMSCs were superior in enhancing new bone growth without donor site morbidity compared to ICABG. The presence of hUCMSCs in tissue-engineered alveolar bone graft (ABG), supported with paracrine activity of the resident stem cells, initiated earlier new bone repopulation, and completed faster bone regeneration. The HA/Cs/Gel scaffold seeded with UCMSCs+BMP-2 is a safe substitute of ICABG to close alveolar bone defects suitable for patients with cleft lip, alveolus, and palate.

Cancer-associated fibroblast (CAF) secretomes-induced epithelial-mesenchymal transition on HT-29 colorectal carcinoma cells associated with hepatocyte growth factor (HGF) signalling.

OBJECTIVE: The aim of this study was to investigate the effect of cancer-associated fibroblasts (CAF) secretomes on the epithelial-mesenchymal transition (EMT) of colorectal carcinoma (CRC) cells and its association with hepatocyte growth factor (HGF) signalling focussing on the HGF receptor, c-Mesenchymal epithelial transition (c-Met), and the EMT markers, vimentin and e-cadherin, in CRC cells. METHODS: Conditioned mediums (CM) containing secretomes from colorectal CAFs and their counterpart normal fibroblasts (NFs) of three CRC patients were collected and supplemented to the HT-29 CRC cells. The mRNA levels of a-smooth muscle actin (a-SMA) and HGF in both fibroblasts, as well as c-Met, vimentin, and e-cadherin in HT-29 cells after supplemented with CAF- and NF-CM were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). HGF protein level in the CM of CAFs and NFs was measured using enzyme-linked immunosorbent assay (ELISA). Vimentin and e-cadherin protein expressions were observed in HT-29 cells using immunofluorescent (IF) staining. RESULTS: Compared to the non-cancerous colon, fibroblasts from cancerous area of CRC substantially expressed higher mRNA levels of a-SMA, a CAF marker. The HGF mRNA expressions in CAFs and NFs were in line with the HGF protein level in the secretomes of both cells. CAF-CM increased c-Met and vimentin mRNA levels in HT-29 cells. Surprisingly, e-cadherin mRNA level in HT-29 cells was increased following CAF-CM supplementation. We also demonstrated the co-localization of e-cadherin and vimentin in the HT-29 cell cytoplasm. CONCLUSIONS: CAF secretomes of CRC promote a hybrid type of EMT associated with HGF signalling.

Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

PURPOSE: The efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) is limited due to drug resistance and cardiotoxic effects. Preclinical studies have shown that statin induces apoptosis and decreases breast cancer cell growth. This study aims to evaluate the role of statin in combination with fluorouracil, adriamycin, and cyclophosphamide (FAC) therapy in LABC patients. MATERIALS AND METHODS: We undertook a randomized, double-blinded, placebo-controlled trial in two centers of Indonesia. Patients were randomly assigned to FAC plus simvastatin (40 mg/day orally) or FAC plus placebo (40 mg/day) for 21 days. The FAC regimen was repeated every 3 weeks. We evaluated the clinical response, pathological response, and toxicities. RESULTS: The objective response rate (ORR) for FAC plus simvastatin was 90% (95% confidence interval [CI], 0.99 to 1.67) by per-protocol analysis. No complete responses (CR) were recorded, but there were 48 partial responses. No significant difference was observed between the two groups with the ORR (p=0.103). The pathological CR rate was 6.25% (2 in simvastatin group and 1 in placebo group). Adverse events in both arms were generally mild, mainly consisted of myotoxicity. Human epidermal growth factor receptor 2 (HER2) expression was a factor related to the success of therapeutic response (odds ratio, 4.2; 95% CI, 1.121 to 15.731; p=0.033). CONCLUSION: This study suggests that simvastatin combined with FAC shows improvements in ORR and pathological response in patients with LABC. Although no statistically significant difference was documented, there was a trend for better activity and tolerability. The addition of 40 mg simvastatin may improve the efficacy of FAC in LABC patients with HER2 overexpression.

Ganglion cells apoptosis in diabetic rats as early prediction of glaucoma: a study of Brn3b gene expression and association with change of quantity of NO, caspase-3, NF-κB, and TNF-α.

AIM: To find a new concept to show whether or not apoptosis of retinal ganglion cells (RGCs) can be determined in the histology of acute hyperglycemia in the role of expressed Brn3b gene related to nitric oxide (NO), caspase-3, nuclear factor kappa-B (NF-κB), and tumor necrosis factor-α (TNF-α) as an early predictor of primary open angle glaucoma (POAG) eyes and their associations. METHODS: Experimental in vivo study was carried out using adult male, white Sprague-Dawley rats aged ≥2mo, weighing 150-200 g. The animals were divided into two groups, one group receiving intraperitoneal injection of streptozotociz 50 mg/kg in 0.01 mol/L citric buffer and pH 4.5 and a comparison made with the control group. Retinal tissue was divided into two parts (both experimental and control groups respectively): a) right retina for immunohistochemistry (IHC; caspase-3 and TNF-α); b) left retina was divided into two parts for the purpose of real-time polymerase chain reaction (PCR) test (RNA extraction for Brn3b gene expression analysis) and ELISA test (NO and NF-κB). RESULTS: The experimental group showed a decrease in Brn3b gene expression compared to the control group (1.3-fold lower in 2nd month; 1.1-fold lower in 4th month and 2.5-fold lower in 6th month). However, there was a decrease of NO, caspase-3, and an increase of NF-κB and TNF-α quantity. CONCLUSION: The expression of mRNA Brn3b gene is inversely proportional to apoptosis in RGCs. The quantity of NO, caspase-3, NF-κB and TNF-α is influential in expression of Brn3b in RGCs caused by hyperglycemia in diabetic rats.

Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer.

OBJECTIVES: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. METHODS: We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. RESULTS: Strong expression of SOX2 (p = 0.011, p = 0.001) and OCT4 (p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). CONCLUSIONS: Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer.

New Bone Formation in Tuberculous-Infected Vertebral Body Defect after Administration of Bone Marrow Stromal Cells in Rabbit Model.

STUDY DESIGN: Preliminary experimental study using a rabbit spondylitis model. PURPOSE: To observe the ossification in a micro-environment containing live Mycobacterium tuberculosis transplanted with bone marrow stromal cells (BMSCs) in rabbits. OVERVIEW OF LITERATURE: BMSCs differentiate to osteoblasts and then osteocytes during ossification. Mycobacterium tuberculosis does not affect BMSC growth in vitro. METHODS: Six rabbits were divided into two groups of three rabbits. One group was positive for spondylitis tuberculosis by culture, polymerase chain reaction (PCR), and histopathologically. The other group was positive by PCR and histopathologically. Both groups were treated using BMSC transplantation and anti-tuberculosis drugs. After 6 weeks, ossification was evaluated by enumerating the number of osteoblasts, osteocytes, and lesion level of calcium. RESULTS: Mean number of osteoblasts was 207.00±31.00 in the first group and 220.33±73.46 in the second group. Mean number of intra-lesions osteocytes was in the first and second group was 18.33±30.04 and 31.00±26.87, respectively. Mean calcium level in the first group and second group was 2.94%±0.89% and 2.51%±0.13%, respectively. Total ossification score in the first and second group was 31.00 and 25.67, respectively. CONCLUSIONS: Mycobacterium tuberculosis provides support for new bone formation by stimulating intra-lesion calcium metabolism. The microscopic environment containing live Mycobacterium tuberculosis enhances ossification.

Fibrodysplasia Ossificans Progressiva: Difficulty in Diagnosis and Management A case report and literature review.

INTRODUCTION: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant genetic disorder and characterized by postnatal progressive heterotopic ossification of the connective tissue. There are difficulties in diagnosing FOP, thus delayed or misdiagnosis and mismanagement is common. 3D printers have now become widely available and inexpensive, and can be used to rapidly produce life-size models based on CT scans of an individual patient. The availability of patient specific, accurate and detailed models of complex acetabular fractures can aid planning of surgical management on a patient specific basis. CASE REPORT: We present the diagnosis and surgical management of a 9-year old Indonesian girl with FOP. She presented with extensive involvement of cervical spine and both shoulders. Total excision of occipito-cervico-lumbar and paravertebral ossification and also exostoses at bilateral shoulder was done. At three years follow up, she had local recurrence with similar range of movement of the shoulder and cervical spine. CONCLUSION: FOP is an extremely rare case. It is difficult to diagnose and manage FOP, therefore delayed or misdiagnosis and also inappropriate management is common.

Overexpression and amplification of Murine double minute 2 as a diagnostic tool in large lipomatous tumor and its correlation with Ki67 proliferation index: an institutional experience.

CONTEXT: Well-differentiated liposarcoma (WDLPS) is the most common type of liposarcoma and sometimes can be difficult to distinguish from large lipoma due to the similar morphology. AIMS: This study proposed to evaluate the expression and amplification of Murine double minute 2 (MDM2) gene and determine its correlation with Ki67 proliferation index. SETTINGS AND DESIGN: This study used cross-sectional design. MATERIALS AND METHODS: This study enrolled 37 cases of lipomatous tumors with >5 cm in size. Eighteen cases of WDLPS and 19 cases of lipoma were stained for MDM2 and Ki67 immunohistochemistry, followed by MDM2 in situ hybridization in 12 selected cases. STATISTICAL ANALYSIS USED: MDM2 overexpression and amplification status for both groups were compared using Chi-square test, with the alternative of Fisher's exact test. Correlation test between MDM2 overexpression and clinical characteristics with the Ki67 proliferation index were performed using Pearson's test with the alternative of Spearman's rho test. RESULTS: MDM2 overexpression was detected in all WDLPS cases and in 3 (16%) of lipoma cases with significance difference (P = 0.000), whereas MDM2 amplification was found in all WDLPS and in 1 of lipoma cases (P = 0.200). There was a strong correlation between MDM2 overexpression and higher Ki67 proliferation index (r = 0.645, P = 0.000). CONCLUSION: Evaluation of MDM2 overexpression can be used as a useful adjunct to differentiate WDLPS from large lipoma and seems to be related with Ki67 proliferation index.