Fibromatosis-like metaplastic carcinoma of the breast has a claudin-low immunohistochemical phenotype

Abstract

Fibromatosis-like metaplastic carcinoma (FLMCa) of the breast is a rare low-grade spindle cell carcinoma, of which the biological characteristics have not been well studied. This study aims to assess, in FLMCa, immunohistochemical expression of claudins (CLDN) and features connected with the claudin-low subtype, such as the presence of tumor initiating cells (TIC), epithelial-mesenchymal transition (EMT) phenotype, as well as EGFR activating mutations. Three cases of FLMCa were retrieved from our hospital archives. Histological and immunohistochemical characteristics were reviewed. Expression of CLDN-1, CLDN-3, CLDN-4 and CLDN-7, CD44 and CD24 (TIC phenotype), and vimentin and E-cadherin (EMT features) were studied. EGFR mutations on exons 18, 19, 20, and 21 were investigated by real-time PCR. In all cases, the low-grade spindle cell component was predominant, with two cases presenting <5 % of epithelioid and squamous areas. The tumors expressed basal cytokeratins and vimentin and were hormone receptor and ERBB2 negative. CLDN membrane expression was negative in the spindle cell component. The epithelioid areas were CLDN-1 positive. Nuclear/cytoplasmatic expression of CLDN-4 was observed in all components, except in one case in which it was strongly expressed in the non-spindle areas. All three cases were CD44+/CD24-. E-cadherin was focally expressed in epithelioid cells, only in the squamous areas. Activating EGFR mutations were not found. One patient developed local recurrences, metastases and died. FLMCa have the immunohistochemical profile of claudin-low breast tumors, with low expression of adhesion molecules, presence of TIC and EMT phenotype. No EGFR activating mutations were found.