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Automated image analysis of cyclin D1 protein expression in invasive lobular breast carcinoma provides independent prognostic information

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Author

  • Nicholas P. Tobin
  • Katja L. Lundgren
  • Catherine Conway
  • Lola Anagnostaki
  • Sean Costello
  • Göran Landberg

Summary, in English

The emergence of automated image analysis algorithms has aided the enumeration, quantification, and immunohistochemical analyses of tumor cells in both whole section and tissue microarray samples. To date, the focus of such algorithms in the breast cancer setting has been on traditional markers in the common invasive ductal carcinoma subtype. Here, we aimed to optimize and validate an automated analysis of the cell cycle regulator cyclin D1 in a large collection of invasive lobular carcinoma and relate its expression to clinicopathologic data. The image analysis algorithm was trained to optimally match manual scoring of cyclin D1 protein expression in a subset of invasive lobular carcinoma tissue microarray cores. The algorithm was capable of distinguishing cyclin D1 positive cells and illustrated high correlation with traditional manual scoring (kappa = 0.63). It was then applied to our entire cohort of 483 patients, with subsequent statistical comparisons to clinical data. We found no correlation between cyclin D1 expression and tumor size, grade, and lymph node status. However, overexpression of the protein was associated with reduced recunrrence-free survival (P = .029), as was positive nodal status (P < .001) in patients with invasive lobular carcinoma. Finally, high cyclin D1 expression was associated with increased hazard ratio in multivariate analysis (hazard ratio, 1.75; 95% confidence interval, 1.05-2.89). In conclusion, we describe an image analysis algorithm capable of reliably analyzing cyclin D1 staining in invasive lobular carcinoma and have linked overexpression of the protein to increased recurrence risk. Our findings support the use of cyclin D1 as a clinically informative biomarker for invasive lobular breast cancer. (C) 2012 Elsevier Inc. All rights reserved.

Department/s

Publishing year

2012

Language

English

Pages

2053-2061

Publication/Series

Human Pathology

Volume

43

Issue

11

Document type

Journal article

Publisher

Elsevier

Topic

  • Cell and Molecular Biology
  • Cancer and Oncology

Keywords

  • Automated image analysis
  • Cyclin D1
  • Invasive lobular breast carcinoma
  • Recurrence-free survival

Status

Published

Research group

  • Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1532-8392