Automated image analysis of cyclin D1 protein expression in invasive lobular breast carcinoma provides independent prognostic information.
Affiliation
Breakthrough Breast Cancer Research Unit, School of Cancer, Enabling Sciences and Technology, University of Manchester, Manchester Academic Health Science Centre, Paterson Institute for Cancer Research, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UKIssue Date
2012-11
Metadata
Show full item recordAbstract
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 (κ = 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 recurrence-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.Citation
Automated image analysis of cyclin D1 protein expression in invasive lobular breast carcinoma provides independent prognostic information. 2012, 43 (11):2053-61 Hum PatholJournal
Human PathologyDOI
10.1016/j.humpath.2012.02.015PubMed ID
22647349Type
ArticleLanguage
enISSN
1532-8392ae974a485f413a2113503eed53cd6c53
10.1016/j.humpath.2012.02.015
Scopus Count
Collections
Related articles
- Expression and amplification of cyclin D1 in primary breast carcinomas: relationship with histopathological types and clinico-pathological parameters.
- Authors: Naidu R, Wahab NA, Yadav MM, Kutty MK
- Issue date: 2002 Mar-Apr
- Prognostic value of cell cycle regulator molecules in surgically resected stage I and II breast cancer.
- Authors: Peters MG, Vidal Mdel C, Giménez L, Mauro L, Armanasco E, Cresta C, Bal de Kier Joffé E, Puricelli L
- Issue date: 2004 Nov
- Cyclin D1 overexpression associates with favourable prognostic factors in invasive breast carcinoma.
- Authors: El-Hafez AA, El Aaty Shawky A, Hasan B
- Issue date: 2012
- Frequent overexpression of the cyclin D1 oncogene in invasive lobular carcinoma of the breast.
- Authors: Oyama T, Kashiwabara K, Yoshimoto K, Arnold A, Koerner F
- Issue date: 1998 Jul 1
- Abnormal expression of cell cycle regulatory proteins in ductal and lobular carcinomas of the breast.
- Authors: Geradts J, Ingram CD
- Issue date: 2000 Sep