1.Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate
The Malaysian Journal of Pathology 2018;40(2):103-110
Introduction: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. Methods: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. Results: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). Conclusion: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.
ethnic variation
2.The role of heat shock proteins and glucose regulated proteins in cancer
Jia Shin Jessica Tan ; Kien Chai Ong ; Anthony Rhodes
The Malaysian Journal of Pathology 2016;38(2):75-82
Heat shock proteins (HSPs) are a family of evolutionary conserved proteins that work as molecular
chaperones for cellular proteins essential for cell viability and growth as well as having numerous
cyto-protective roles. They are sub-categorised based on their molecular weights; amongst which
some of the most extensively studied are the HSP90 and HSP70 families. Important members of
these two families; Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90), are the glucose
regulated proteins (GRP). These stress-inducible chaperones possess distinct roles from that of the
other HSPs, residing mostly in the endoplasmic reticulum and mitochondria, but they can also be
translocated to other cellular locations. Their ability in adapting to stress conditions in the tumour
microenvironment suggests novel functions in cancer. GRPs have been implicated in many crucial
steps of carcinogenesis to include stabilization of oncogenic proteins, induction of tumour angiogenesis,
inhibition of apoptosis and replicative senescence, and promotion of invasion and metastasis.
3.Polymorphisms in the androgen receptor CAG repeat sequence are related to tumour stage but not to ERG or androgen receptor expression in Malaysian men with prostate cancer
The Malaysian Journal of Pathology 2019;41(3):243-251
Introduction: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene
may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG
fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed
in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression
of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients
relate this to the length of the CAG repeat sequence in their AR gene. Materials and Methods:
From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood
and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR
gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and
compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies.
Results: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign
prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in
men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or
tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were
expressed in 36% and 86% of the cancers, respectively. There was no significant association between
CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship
between ERG and AR expression. In addition, a significantly great proportion of Indian men had
ERG positive tumours, compared to men of Malay or Chinese descent. Conclusions: CAG repeat
length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears
to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of
other Malaysian ethnicities and its expression in this study was inversely related to AR expression.