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.

Introduction: According to the predefined 2010 World Health Organisation criteria, serrated colonic polyps (SCP) are pathologically classified into hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia and traditional serrated adenoma (TSA). Sessile serrated adenoma/polyp is acknowledged as a precursor of colorectal carcinoma through the serrated neoplastic pathway. Hyperplastic polyps display similar histological features to SSA/P, in comparison to other types of SCP. It is noteworthy to discriminate between HP and SSA/P, since only the latter has a malignant potential. Method: A total of 198 cases of SCP were identified and the slides were reexamined and reclassified accordingly. Analysis on the proportion of SSA/P among SCP and underdiagnosed cases of SSA/P was performed. The association between SSA/P and non-SSA/P with demographic data and colonoscopic findings were also studied. Results: From the 198 cases of SCP, 164, 29 and five cases were reclassified as HP, SSA/P and TSA respectively. Sixteen cases of SSA/P were underdiagnosed as HP. From among 29 cases of SSA/P, the majority were ≥ 65 years old (17; 58.6%), male (21; 72.4 %) and Chinese (17; 58.6%). Most of the SSA/P (16; 55.2 %) were located in the right colon and measured ≥ 10mm (9; 31%) in size. Location (p=0.004) and size (p=0.013) of the colonoscopic findings were significantly associated with SSA/P. Conclusion: Underdiagnosed cases of SSA/P among HP were identified most likely because of the resemblance of their histological features. The location and size of SCP may suggest the probability of SSA/P.

Introduction: Endometrial carcinoma is the most common gynaecological malignancy in developed countries and the sixth most common cancer among women worldwide. Cancer staging is vital in treatment decisions and the prediction of prognoses, and is based on imaging studies, histological results and surgery. Therefore, a simple and fast preoperative tool to predict the precise cancer stage of patients is needed. CA 125, a cancer antigen, is used in assessing therapeutic response and cancer surveillance in endometrial carcinoma. However, this tumour marker is not routinely performed in the mentioned circumstances. Studies have shown that preoperative CA 125 was significantly high in patients in a higher stage of endometrial cancer. Thus, this study aims to assess the primary role of CA 125 in predicting the stage of endometrial carcinoma, by correlating preoperative serum CA 125 with clinicopathological parameters. Method: The retrospective data of endometrial carcinoma cases consisting of demographic and clinicopathological parameters as well as preoperative serum CA 125 levels were retrieved from Laboratories Information System (LIS) at Hospital Selayang, Selangor, Malaysia, from January 2000 until June 2016. Only 20 cases fulfilled the inclusion and exclusion criteria. Preoperative serum CA 125 was correlated with demographic and clinicopathological parameters, and was analysed using a Kruskal-Wallis test. Results: There was a significant association between elevated serum CA 125 with myometrial and cervical stroma invasion in endometrial carcinoma (p<0.05). Conclusion: Preoperative serum CA 125 is a useful marker in predicting early stages of endometrial carcinoma, and plays a role in pre-operative cancer staging in endometrial carcinoma.