6533b824fe1ef96bd1281637

RESEARCH PRODUCT

Cytokeratin 8 immunostaining pattern and E-cadherin expression distinguish lobular from ductal breast carcinoma.

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Immunohistochemistry using antibodies to cytokeratin 8 can serve as a valuable diagnostic tool for the differentiation of lobular from ductal carcinomas of the breast. In contrast with ductal carcinomas, which exhibit a peripheral-predominant immunostaining pattern, adjacent tumor cells “molding” to each other, lobular carcinomas exhibit a ring-like perinuclear immunostaining pattern, creating a “bag of marbles” appearance with neighboring tumor cells. This immunostaining pattern is stable even in the tumors that otherwise do not exhibit characteristic histomorphologic features (ie, solid or pleomorphic type of a lobular carcinoma) and tumors that mimic growth patterns characteristic of the respective other tumor type (ie, targetoid or single-file growth pattern in a ductal carcinoma). Furthermore, we demonstrate that ductal carcinomas express E-cadherin in a similar peripheral-predominant immunostaining pattern (33/33 cases), while all 15 lobular carcinomas were negative for E-cadherin, suggesting a role for E-cadherin in the architectural organization of the cytoskeletal scaffolding within the tumor cells. Infiltrating lobular carcinoma of the breast, which accounts for roughly 10% to 15% of breast cancer cases, is distinguished histologically from infiltrating ductal carcinoma by its characteristic small cells with inconspicuous nucleoli. Lobular carcinomas demonstrate a different infiltrative pattern, typically as linear arrays (files) or single cells, and classically forming targetoid patterns around nonneoplastic ducts. 1 Infiltration typically occurs in a manner that does not destroy anatomic structures or excite a substantial connective tissue response. Pure lobular carcinomas have been associated with a prolonged disease-free survival compared with cases of infiltrating ductal carcinoma, in particular during the early stages of the disease. 2,3 However, a number of variants of invasive lobular carcinoma have been described, including solid, alveolar, mixed, histiocytoid, tubulolobular, and pleomorphic types, the latter exhibiting moderate to high nuclear grades. Besides their characteristic histologic features, these variants are characterized by an increased risk of recurrence and an overall less favorable prognosis than classic lobular carcinoma. 4