BACR4
Expression of embryonic stem cell markers, OCT4 and NANOG, in breast, thyroid, brain and colorectal carcinomas
Zahra Madjd1, Forogh Hashemi2, Nasrin Shayanfar2, Amir H Zarnani4, Enseieh Farahani1, Ahmad Makhmalbaf2, Ali M. Sharifi3
1Oncopathology Research Centre, Iran University of Medical Sciences, Tehran, Iran 2Dep Pathology, Iran University of Medical Sciences, Tehran, Iran, 3Cellular Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran, 4Reproductive Biotechnology Research Centre, Avesina Research Institute, Tehran, Iran
Background
According to cancer stem cell (CSC) concept, only a subpopulation of cells within a tumour are tumourigenic, which are responsible for maintaining the tumour mass. A number of factors that govern the fate of adult stem cells also play a role in malignant cell transformation. OCT4 and NANOG are key regulators of self-renewal and pluripotency in embryonic stem cells (ESC). Expression of such genes is correlated with tumourigenesis, tumour recurrence or resistance to therapies. Therefore these genes may either play a direct role in different types of carcinoma progression or serve as valuable markers of tumourigenesis.
Method
Immunohistochemistry was used to assess the expression of embryonic stem cell markers OCT4 and NANOG on a panel of tumours including breast, thyroid, brain and colorectal carcinomas. The level of expression of these proteins was then compared to different tumour types and degree of differentiation.
Results
Nanog and OCT4 were expressed at the highest levels on nuclear site of seminoma compared with other tumours. These proteins were detectable in both nucleus and the cytoplasm of breast carcinoma cells, whereas normal breast tissue did not express detectable levels of any stem cell genes. Expression of OCT4 and NANOG was also noted on poorly differentiated papillary carcinoma of thyroid compared to normal follicles of thyroid gland adjacent to tumour as well as nuclei of colorectal carcinomas and metastatic brain tumours.
Conclusion
The intensity of immunoreactivity was variable among positive cells, suggesting that the cells within tumours are heterogeneous in terms of NANOG and OCT4 expression. These carcinomas express elevated levels of embryonic stem cell, showing that these tumours may contain cells indicative of embryonic-like stem cells. Identification of CSC in different malignant tumours leading to a new strategy for targeting the CSCs and may help to cure cancer recurrence and metastasis.
