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Stromal Signatures of Breast Carcinogenesis in Fibroadenoma-A Pilot Study

Rani Kanthan, Jenna-Lynn Senger and Kanthan SC

Background: Fibroadenoma (FA) is a benign breast neoplasm associated with an increased risk of subsequent carcinogenesis; yet, the relationship between these two events remains undetermined. Traditional breast paradigms that focus on the epithelial cell as the primary origin of cancer need to be revisited. Our working hypothesis is that, stromal dysfunction through epithelial-stromal ‘cross-talk’ in the host microenvironment is perhaps the earliest initiating event in breast carcinogenesis.
 
Methods: 60 cases of randomly selected FA were analyzed in this study. Paraffin embedded tissue samples were analyzed using the antibodies TAG72, ErbB2, p53, CD10, Ki67, Bcl2, CD31, Nestin, and Laminin. Stromal and epithelial components were scored and compared on a semi-quantitative scale.
 
Results: Six of the 60 cases subsequently developed breast cancer between 1-12 years after the diagnosis of FA. Comparison of the stromal:epithelial (S:E) ratio of immunohistochemical scores yielded four significant trends suggestive of stromal dysfunction. In pre-cancerous lesions, S:E ratios of non-cancerous vs. pre-cancerous FA were lower for a) CD10 at 40:100 vs. 15:95 (p=0.045), b) Bcl2 at 40:85 vs. 20:80 (p=0.048), c) CD31 at 30:0 vs. 9:0 (p=0.0156) and d) Nestin at 40:80 vs. 15:80 (p=0.013).
 
Conclusion: This preliminary study suggests early alterations in the stroma precede development of the epithelial phenotype of breast cancer. Improved understanding of host stromal microenvironmental changes can lead to the recognition of ‘stromal signatures’ as risk assessment markers in FA for future breast carcinogenesis. In the future, exploration in both benign and malignant proliferations of breast lesions should be undertaken to further elucidate these ‘stromal signatures’ in breast cancer for men and women.