On integration into the host cervical keratinocyte genome, human papillomavirus (HPV) E7 protein binds pRB, releasing E2F from normally incompetent pRB-E2F complexes and allowing propagation of G1-S transition by the E2F. p16 INK4a, a tumour suppressor protein, increases in refl ex response to counter this. 29 histologically re-confi rmed low-grade squamous intraepithelial lesions (LSIL), 27 high-grade squamous intraepithelial lesions (HSIL) and 30 invasive cervical squamous carcinoma (SCC) were immunohistochemically stained for p16INK4a expression using the CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany) to re-affi rm the notion that integration of HPV occurs predominantly in SCC and possibly HSIL and less in LSIL and normal squamous epithelium (NSqE). Implicit was also the attempt to understand the role of E2F, as indicated by p16INK4a, in evolution of SCC from HSIL. No ethnic predilection was noted for LSIL, HSIL or SCC. Patients with SCC were signifi cantly older by about 14-years compared with HSIL (p<0.05) while there was no signifi cant age difference between HSIL and LSIL. p16INK4a expression was signifi cantly increased (p<0.05) in both HSIL (88.9%) and SCC (83.3%) compared with LSIL (3.4%) and NSqE (0%); the NSqE being normal squamous epithelium noted in 17 of the LSIL, 19 HSIL and 5 SCC. From these fi ndings there is suggestion that fundamental upstream events viz HPV integration, E7 upregulation followed by E2F activation occurs at point of transformation to HSIL and continues unrelentingly for another one to two decades before hitherto unclear factors convert a non-invasive lesion into an overtly invasive malignant counterpart. Interestingly, the occurrence of HSIL and LSIL in almost the same age group could mean that alteration from episomal to integrated form of HPV may not incur a prolonged incubation period, unlike from HSIL to SCC

Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profi les of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplifi cation by FISH, a small but certain percentage of patients would miss the benefi t of anti-cerbB- 2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to signifi cant ramifi cations on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.

In Malaysia, dialysis-treated end stage renal disease (ESRD) patients have been increasing rapidly. Haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) use a disproportionately large amount of limited healthcare resources. This study aims to estimate the costs of HD and CAPD from the Ministry of Health (MOH) perspective. One year prospective multicentre study was conducted from October 2016 to September 2017 to assess direct medical costs of 90 HD patients and 73 CAPD patients from five large MOH dialysis centres. A mixed method of activity-based costing and step-down was used. The capital costs included land, building, medical equipment and furnishing. The recurrent costs included staff emoluments, facility utilities, patients’ medical costs and dialysis consumables. One-way sensitivity analysis was performed to investigate variability in the data. One hundred and forty-one patients (82%) completed the study comprising of 77 patients on HD and 64 patients on CAPD. Majority of the patients were between 46-65 years old (n=75, 53.2%). The most common aetiology of ESRD was diabetes mellitus (44.2% in HD and 48.4% in CAPD). Cost per patient per year was RM39,790 for HD and RM37,576 for CAPD. The main cost drivers were staff emoluments (37.6%) and dialysis consumables (70.5%) for HD and CAPD respectively. HD is highly sensitive towards all the variables analysed except for dialysis consumables. In CAPD, there are minimal sensitivities except for the 5% discount rate. Knowledge of the costs of modalities are useful in the context of planning for dialysis services and to optimise the number of kidney failure patients treated by dialysis within the MOH.
Haemodialysis ; continuous ambulatory peritoneal dialysis ; end stage renal disease ; cost ; Malaysia