A Retrospective Hospital-Based Study of HMGCR Expression in HER2 IHC 2+ and 3+ Breast Cancer.

Malisalaora Mohamed,Hasnan Jaafar,Noorasmaliza Paiman,Siti Norasikin Mohd Nafi

doi:10.31557/apjcp.2021.22.7.2043

Abstract

Objective:The role of HMG-CoA reductase (HMGCR) in relation to prognostic and treatment predictive information of HER2 positive breast cancer has been newly explored. In this study, we aimed to determine the expression of HMGCR in HER2 immunohistochemistry (IHC) scores of 2+ and 3+ breast cancer and to correlate with the patients’ outcomes.Methodology:Using a cross-sectional design, invasive breast carcinoma of no special type (NST) and HER2 IHC scores of 2+ and 3+ cases were selected over a 50-month period in Hospital Sultanah Bahiyah (HSB), Alor Setar. IHC staining for HMGCR was performed on paraffin-embedded tissues at the Pathology Laboratory, Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian using the standard staining procedure. The results were correlated with the patient’s demographic and clinicopathological data. Results:A total of 59 cases of HER2 IHC 2+ and 3+ invasive breast carcinoma were identified. The cases were predominant in young Malay women with tumours smaller than 50mm, higher grade and positive for lymphovascular invasion, axillary lymph nodes involvement and ER/PR expressions. HMGCR was positively expressed in HER2 IHC 2+ and 3+ breast cancer cases, which the staining intensities varied from weak, moderate to strong. Majority of the cases were scored 1+ for HMGCR expression. A low-positive HMGCR was more likely to be associated with less favourable outcomes of patients with HER2 IHC 2+ and 3+. However, the associations were statistically not significant. Conclusion:A study in a larger cohort of tumour samples is needed to further validate HMGCR expression as a potential prognostic biomarker for HER2 positive breast cancer. It is also suggested that all the HER2 IHC 2+ and 3+ cases need to be gene amplified using FISH analysis.

Highlights

The Malaysia National Cancer Registry Report stated an increase in female cancer cases in Malaysia from 20122016 (Registry, 2019)
Using a cross-sectional design, invasive breast carcinoma of no special type (NST) and HER2 IHC scores of 2+ and 3+ cases were selected over a 50-month period in Hospital Sultanah Bahiyah (HSB), Alor Setar
HMG-CoA reductase (HMGCR) was positively expressed in HER2 IHC 2+ and 3+ breast cancer cases, which the staining intensities varied from weak, moderate to strong

Summary

Introduction

The Malaysia National Cancer Registry Report stated an increase in female cancer cases in Malaysia from 20122016 (Registry, 2019). Among all female cancer subtypes, breast cancer has been reported the most common cancer among Malaysian population (Observatory, 2020). 30% of Malaysian female breast cancer patients are HER2-positive, which categorises an aggressive subtype (Tan et al, 2009). The utilization of trastuzumab, a monoclonal anti HER2 is the foundation of systemic treatment of HER2 positive breast cancer (Gajria and Chandarlapaty, 2011). Regardless of its noteworthy effect on HER2 positive breast cancer, resistance to trastuzumab remains a challenge, requesting further research to be done. Previous study suggests high cholesterol as a risk factor for breast cancer (Murai, 2015). A current study have evaluated the role of HMGCR in relation to prognostic and treatment predictive information of HER2 positive breast cancer (Sethunath et al, 2019). We aimed to determine the expression of HMGCR in HER2 IHC scores of 2+ and 3+ breast cancer and to correlate the expression with the patients’ outcomes

Materials and Methods

Results

Discussion