Detection of Human Cytomegalovirus Proteins in Paraffin-Embedded Breast Cancer Tissue Specimens-A Novel, Automated Immunohistochemical Staining Protocol.

Joel Touma,Torill Sauer,Jürgen Geisler,Katja Vetvik,Yan Liu,Cecilia Söderberg-Nauclér,Afsar Rahbar,Nerea Martin Almazan,Mattia Russel Pantalone

doi:10.3390/microorganisms9051059

Abstract

Emerging evidence supports a significant association between human cytomegalovirus (HCMV) and human malignancies, suggesting HCMV as a human oncomodulatory virus. HCMV gene products are found in >90% of breast cancer tumors and seem to be correlated with more aggressive disease. The definitive diagnosis of HCMV relies on identification of virus inclusions and/or viral proteins by different techniques including immunohistochemical staining. In order to reduce biases and improve clinical value of HCMV diagnostics in oncological pathology, automation of the procedure is needed and this was the purpose of this study. Tumor specimens from 115 patients treated for primary breast cancer at Akershus University Hospital in Norway were available for the validation of the staining method in this retrospective study. We demonstrate that our method is highly sensitive and delivers excellent reproducibility for staining of HCMV late antigen (LA), which makes this method useful for future routine diagnostics and scientific applications.

Highlights

Breast cancer is the most commonly diagnosed malignancy and leading cause of cancer related death among women worldwide, where 1 out 8 women are at risk of developing the disease during their lifetime [1], this malignancy is a major public health problem and global data predict incidence and mortality to still be on the rise [2]
We found that 83 out of 111 (~75%) of the breast cancer patient samples were positive for human cytomegalovirus (HCMV) late antigen (LA) in tumor tissue and/or lymph node metastasis from breast cancer, and 9 out of 111 (~8%) samples were positive for HCMV immediate early (IE) proteins (Table 2)
We found that 83 out of 111 (~75%) of the breast cancer patient samples were positive for HCMV LA and 9 out of 111 (~8%) samples were positive for HCMV IE proteins (Table 2)

Summary

Introduction

Breast cancer is the most commonly diagnosed malignancy and leading cause of cancer related death among women worldwide, where 1 out 8 women are at risk of developing the disease during their lifetime [1], this malignancy is a major public health problem and global data predict incidence and mortality to still be on the rise [2]. Some of the known risk factors for this malignancy include age, early age at menarche, late age of menopause, hormone replacement therapy usage, and positive family history [4]. Up to 80% of patients diagnosed with breast cancer do not present with any of the known risk factors and the disease is considered sporadic [4]. The etiology remains unclear for the majority of breast cancer patients and it is important to further 4.0/).

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