Automated image analysis of cyclin D1 protein expression in invasive lobular breast carcinoma provides independent prognostic information
Författare
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.
Avdelning/ar
Publiceringsår
2012
Språk
Engelska
Sidor
2053-2061
Publikation/Tidskrift/Serie
Human Pathology
Volym
43
Issue
11
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Cell and Molecular Biology
- Cancer and Oncology
Nyckelord
- Automated image analysis
- Cyclin D1
- Invasive lobular breast carcinoma
- Recurrence-free survival
Status
Published
Forskningsgrupp
- Pathology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1532-8392