Centrosome amplification: a quantifiable cancer cell trait with prognostic value in solid malignancies
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CLINICAL
Centrosome amplification: a quantifiable cancer cell trait with prognostic value in solid malignancies Karuna Mittal 1 & Jaspreet Kaur 1 & Meghan Jaczko 1 & Guanhao Wei 1 & Michael S. Toss 2 & Emad A. Rakha 2 & Emiel Adrianus Maria Janssen 3 & Håvard Søiland 4 & Omer Kucuk 5 & Michelle Dian Reid 6 & Meenakshi V. Gupta 7 & Ritu Aneja 1 Received: 4 September 2020 / Accepted: 12 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Numerical and/or structural centrosome amplification (CA) is a hallmark of cancers that is often associated with the aberrant tumor karyotypes and poor clinical outcomes. Mechanistically, CA compromises mitotic fidelity and leads to chromosome instability (CIN), which underlies tumor initiation and progression. Recent technological advances in microscopy and image analysis platforms have enabled better-than-ever detection and quantification of centrosomal aberrancies in cancer. Numerous studies have thenceforth correlated the presence and the degree of CA with indicators of poor prognosis such as higher tumor grade and ability to recur and metastasize. We have pioneered a novel semi-automated pipeline that integrates immunofluorescence confocal microscopy with digital image analysis to yield a quantitative centrosome amplification score (CAS), which is a summation of the severity and frequency of structural and numerical centrosome aberrations in tumor samples. Recent studies in breast cancer show that CA increases across the disease progression continuum, while normal breast tissue exhibited the lowest CA, followed by cancer-adjacent apparently normal, ductal carcinoma in situ and invasive tumors, which showed the highest CA. This finding strengthens the notion that CA could be evolutionarily favored and can promote tumor progression and metastasis. In this review, we discuss the prevalence, extent, and severity of CA in various solid cancer types, the utility of quantifying amplified centrosomes as an independent prognostic marker. We also highlight the clinical feasibility of a CA-based risk score for predicting recurrence, metastasis, and overall prognosis in patients with solid cancers. Keywords Centrosome amplification . Prognostic biomarker . Solid tumors . Formalin-fixed paraffin-embedded tissue sections . DCIS
1 Introduction * Ritu Aneja [email protected] 1
Department of Biology, Georgia State University, 100 Piedmont Ave, Atlanta, GA 30303, USA
2
Department of Pathology, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
3
Department of Pathology, Stavanger University Hospital, Stavanger, Norway
4
Department of Breast and Endocrine Surgery, Stavanger University Hospital, Stavanger, Norway
5
Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University Hospital, Atlanta, GA, USA
6
Department of Pathology, Emory University Hospital, Atlanta, GA, USA
7
Chestatee Pathology, Atlanta, GA, USA
Over a century ago, Edouard van Beneden (1883) discovered a minute cell organelle [
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