Expression of HER Receptor Proteins in Prostate Adenocarcinoma: A Perspective from North Central Nigeria

O I Ajetunmobi,O Odujoko,O A Oguntunde,R Buettner,O D Dzuachii,R A Vhritherire,O S Raphael,U Drebber

doi:10.4236/ojpathology.2019.93007

Abstract

Introduction: Members of the Human Epidermal Receptor [HER] family of receptor tyrosine kinases, such as HER2 and EGFR proteins are overexpressed in several epithelial malignancies and serve as effective therapeutic targets in cancer management. However, their role in prostate cancer development has been sparingly explored and with contrasting findings. Notably their relationship with prostate cancers cases seen in Sub-Saharan Africa is yet to be explored. Design: A retrospective study involving histologically diagnosed cases of adenocarcinomas of the prostate. Cases were classed according to the WHO/ISUP Gleason Prognostic groups [G1 - G5]. Immunohistochemical analysis was performed using monoclonal antibodies for HER2 and EGFR, while in situ hybridization employed DNA probes for the corresponding genes. Scores of +2 and +3 were regarded as positive for both antibodies, while a target gene: centromere ratio of >2 was set as the threshold for amplification. Results: A total of 44 cases were included in the study. The acinar type was the commonest morphologically, with Gleason group 5 [Gleason scores 8 - 10] accounting for close to half of the cases [47.7%]. The HER2 antibody stained negatively in the majority of cases [93.2%], being positive in only 3 [6.8%] of cases seen. High level expression of EGFR [+2/+3] was observed in 25% of cases, low level expression was identified in 6 [13.6%] cases. All HER2 positive malignancies displayed overexpression of EGFR. In situ-hybridization revealed the absence of high level amplification for both HER2 and EGFR, while polysomy was not detected in any of the cases. Conclusion: The overexpression of EGFR in prostate cancers has been demonstrated in a native African population, affirming its suitability for targeted therapy. Overexpression of HER2 in prostate cancer is inconstant, and amplification of the HER2 gene is less frequent than as compared to malignancies of the Breast and Ovary. There’s a need for a standardized protocol for assessing HER2 in prostate cancer.

Highlights

Members of the Human Epidermal Receptor [HER] family of receptor tyrosine kinases, such as HER2 and EGFR proteins are overexpressed in several epithelial malignancies and serve as effective therapeutic targets in cancer management
In situ-hybridization revealed the absence of high level amplification for both HER2 and EGFR, while polysomy was not detected in any of the cases
Gene amplification of HER2 has been found in up to a third of breast cancers, while amplification of the EGFR gene is found in 40% of Glioblastoma multiforme [GBM] and 5% - 10% of non-small cell lung carcinomas [NSCLCs] [1] [2]

Summary

Introduction

Members of the Human Epidermal Receptor [HER] family of receptor tyrosine kinases, such as HER2 and EGFR proteins are overexpressed in several epithelial malignancies and serve as effective therapeutic targets in cancer management Their role in prostate cancer development has been sparingly explored and with contrasting findings. The HER receptor family of receptor tyrosine kinases [RTK] includes proteins such as Epidermal Growth factor Receptor [EGFR], HER2/c-erbB2, HER3, and HER4 They represent the most extensively studied group of the RTKs especially with regards to their roles in normal mammalian development, physiology and formation of human cancers. Following ligand binding, these receptors undergo conformational changes such as dimerization and autophosphorylation their intrinsic tyrosine kinase residues. Our grasp of their complex function and molecular regulatory networks has fuelled the development of revolutionary therapeutic options in the management of cancers over the last decade [4]

Methods

Results

Conclusion