Introduction: The Hedgehog (Hh) signalling pathway is a developmental signalling pathway involved in normal mammalian developmental and homeostasis of adult renewable tissues. In most adult tissues, this pathway remains silent and previous studies have shown that constitutive activation of Hedgehog signalling pathway leads to various types of malignancies including medulloblastomas, basal cell carcinoma, gastrointestinal, breast and prostate cancer. The purpose of this study was to investigate the immunohistochemical expression of Hedgehog pathway proteins in Diffuse Large B-cell Lymphoma and determine their association with overall survival (OS). Methods: Positive control using normal tonsils were included in each batch of immunohistochemical staining procedure. Results: PTCH1 proteins were highly expressed in DLBCL and showed strong staining intensity in 107 (100%) cases and SMO proteins were expressed in 105 (98.1%) cases. PTCH1 proteins were localised in the nucleus of tumour cells, whereas SMO proteins were mainly localised in the cytoplasm of tumour cells. Positive expression of PTCH1 and SMO proteins and overall survival of DLBCL patients were correlated with age, gender, race and tumour location. There was no significant correlation between the expression of these two proteins with any of the parameters. PTCH1 expression showed significant association with SMO expression (P=0.03). Conclusions: Our findings suggest that high expression of both PTCH1 and SMO may be important in the pathogenesis of DLBCL. However, additional mechanisms that may contribute to the activation of HH signalling in DLBCL needs to be further explored.

Introduction: Lin-11, Isl-1 and Mec-3 domains (LIM) homeobox genes are among the most important sub-families of homeobox genes. These genes are thought to play an important role in cancer. In this study, the protein expression of these genes was examined in urothelial carcinoma of the bladder. The expression pattern of Islet-1 (ISL1) and LIM homeobox 5 (LHX5) across different cancer stages and grades, as well as the association between the protein expression of these genes and patient demographics and clinicopathological features, were examined. Methods: A total of 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues were selected from the Department of Pathology, Hospital Kuala Lumpur and the protein expression of ISL1 and LHX5 was determined using immunohistochemistry. Results: Positive expression of ISL1 and LHX5 was detected in 94% and 98% of the samples, respectively. There were no distinct LHX5 expression patterns associated with different cancer stages, but the proportion of high-expressing tumours was higher in high-grade tumours. In addition, there was a significant association between the expression of LHX5 and tumour grade. The proportion of tumours expressing high levels of ISL1 was found to be highest in later stage tumours. Conclusion: The high percentage of tumours expressing both these genes suggests that ISL1 and LHX5 play an important role in bladder tumourigenesis across multiple stages.

Urothelial carcinoma is a common malignant neoplasm that has a poor prognosis and a high frequencyof recurrence and metastasis. Constant disease surveillance with periodic and long term cystoscopyexamination is necessary for management of the disease. However, the monitoring and therapyregimen is expensive, incurring a massive burden to patients and the government. Therefore, thedevelopment of specific biomarkers for urothelial carcinoma at an early stage and recurrence detectionbecomes a priority. Homeobox genes are a family of genes that are involved in tumourigenesis.They might be potential prognostic markers for urothelial carcinoma. The study investigated theexpression pattern of NANOG which is one of a homeobox gene in different stages and grades ofurothelial carcinoma. NANOG expressions were also correlated with patient demographic factors andclinicopathological parameters. The expression of NANOG in 100 formalin-fixed paraffin-embeddedurothelial carcinoma tissues was determined by immunohistochemistry. Immunohistochemistryshowed positive expression of NANOG in all specimens with detection in the cytoplasm, nucleiand the nuclear membrane of the cancer cells. The immunohistochemical expression of NANOGincreased across stages and grades of the tumour. The expression of NANOG was not significantlyassociated with demographic factors; gender (p = 0.376), race (p = 0.718) and age (p = 0.058) aswell as with most of the clinicopathological parameters; pathological stage (p = 0.144), grade (p =0.625), lymph node involvement (p = 0.174) and distant metastasis (p = 0.228). However, NANOGexpression showed significant correlation with tumour invasion (p = 0.019). We concluded thatNANOG might be a potential biomarker for early diagnosis of urothelial carcinoma of the bladder.

Liposarcoma is one of the most common mesenchymal tumour in adults but it is rare to occur in the breast. Our case was a 50 year old single nulliparous woman who presented with a right breast mass for one year duration. The mass was progressively increasing in size in the last few months. Breast examination showed a huge mass measuring 5 x 8 x 6 cm occupying the entire right breast. Mammogram showed a large homogenous soft tissue mass occupying the entire right breast with foci of calcification. A trucut biopsy showed a cellular tumour which was thought to be an invasive carcinoma. The patient underwent right modified radical mastectomy with axillary clearance. Macroscopy showed a well circumscribed lobulated solid haemorrhagic yellowish tumour mass measuring 180 x 110 x 50 mm. Microscopically the tumour was heterogenous comprising cellular round nonlipogenic mesenchymal cells and loose myxoid areas containing small cells. The typical arborizing ‘chicken wire’ capillaries were observed. Vacuolated lipoblasts were seen. All eleven axillary lymph nodes sampled showed no metastasis. A diagnosis of a myxoid liposarcoma was made. To raise the suspicion of a possible mesenchymal tumour, it is very important for clinicians to relay the clinical and radiological findings to the pathologist to avoid misdiagnosis in a trucut biopsy.

Aflatoxin B1 (AFB1) is a toxin produced by Aspergillus species of fungi. Findings in the literature has shown the potential of probiotic treatment to alleviate AFB1 toxicity. This study explores the effects of Lacticaseibacillus paracasei Shirota (LcS) supplementation on the growth performance, intestinal health, and excretion of faecal AFB1 metabolite of AFB1- exposed rats. Thirty-two male Sprague Dawley rats were divided into control, AFB1, AFB1+LcS and LcS groups. AFB1 was given at a complete dosage of 25 µg AFB1/kg body weight, while LcS supplementation at 2×109 CFU/mL per day for four weeks. The average body weight of the AFB1 group showed no significant increase from week 2 to 4, while other groups had an increment throughout the study. The food intake of the AFB1 and AFB1+LcS groups had significantly reduced throughout the treatment period. AFB1 exposure caused several changes in the histomorphometry parameters but was normalised with LcS supplementation. The AFB1 group showed mild to moderate inflammation in all intestinal parts, whereas only mild inflammation was observed in the jejunum and ileum of the AFB1+LcS group. Faecal Bifidobacterium spp. counts showed an increment in three groups, while the AFB1 group showed a significant reduction. The faecal AFB1 in the AFB1 group was significantly lower than in the AFB1+LcS group. In conclusion, AFB1 affected growth performance and intestinal health, and wherein the effects were alleviated by LcS supplementation. Further investigation on intestinal permeability and serum and urinary AFB1 level is suggested to understand the mechanism of probiotic-AFB1 interaction in alleviating AFB1 toxicity.