Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules

Abstract

Matrix-producing carcinoma of the breast is a well-established entity in the group of metaplastic carcinoma, which is histologically characterized by myxochondroid matrix formation and is extremely rare. We describe here four additional cases of matrix-producing carcinoma of the breast. All cases of matrix-producing carcinoma show nest-like, sheet-like, and cord-like growth of tumor cells with cellular atypia, in addition to scattered cancer cells within myxoid or myxohyalinous stroma. Three of four cases showed an acellular or oligocellular matrix-rich zone in the center of the tumor. Immunohistochemically, cancer cells of all cases were positive for cytokeratins and epithelial membrane antigens and partially positive for sox9 and p63. Aggrecan and type II collagen, which are cartilage-specific matrix molecules, were deposited in the stroma of all cases. Type I and type IV collagens were also deposited on the stroma of all cases. These findings suggest that, although cancer cells of matrix-producing carcinoma of the breast are epithelial, they transdifferentiate to chondrocyte-like cells and produce cartilage-specific matrix molecules, which are useful markers for diagnosing matrix-producing carcinoma. Modern Pathology (2008Pathology ( ) 21, 1282Pathology ( -1292 doi:10.1038/modpathol.2008 published online 11 July 2008 Keywords: aggrecan; collagens; matrix-producing carcinoma; breast; immunohistochemistry; electron-microscopy Matrix-producing carcinoma of the breast is an extremely rare and specialized variant of metaplastic carcinoma of the breast, which is a well-established entity; 1,2 because of its rarity, the features of its stroma have remained unclear.Aggrecan is a cartilage-specific major proteoglycan. 3 This macromolecule deposits in the hypertrophic zones of growth plate cartilage, 4 although it was reported to deposit in the salivary pleomorphic adenoma, which frequently showed mesenchyme-like elements, including myxoid and chondroid tissues. 5,6 Type II collagen, which is a cartilage-specific major collagen, and chondromodulin-I (ChM-I), which is cartilage-specific noncollagenous matrix protein, 4,7,8 are deposited in the normal cartilaginous matrix. These molecules can be useful markers of cartilaginous differentiation. As sox9 is a transcription factor, the expression of which induces cartilaginous differentiation, 9-11 this molecule is also a useful marker of chondroid differentiation in normal and neoplastic tissues. [9][10][11][12] We investigated the deposition of matrix molecules in matrix-producing carcinoma of the breast, histochemically and immunohistochemically.

Distinctive Features of Advancing Breast Cancer Cells and Interactions with Surrounding Stroma Observed Under the Scanning Electron Microscope

“…In order to metastasise, tumour cells need to invade across the surrounding ECM where the majority of stroma is fibrillar collagen, particularly collagen type I (Provenzano et al, 2006 andKusafuka et al, 2008). Collagens are the main structural proteins responsible for the structural integrity of vertebrates and many other multicellular organisms (Luparello et al, 1991).…”

Intracellular Location of the SOX9 Protein in Breast Disease

“…We also found, however, consistent expression of SOX9 in over 90% of normal breast epithelial cell nuclei and in the nuclei of a vast majority of lobular carcinomas as well. Kusafuka et al found less nuclear expression in the areas of typical carcinoma in their 4 metaplastic breast carcinoma cases [10]. Likewise, in our ductal breast carcinomas that did not exhibit any metaplastic features, SOX9 was occasionally absent.…”

“…Its up-regulation by retinoic acid receptor agonists suggests it may play a role in normal breast physiology [19]. A recent report identified SOX9 in the nucleus of 4 out of 4 metaplastic breast carcinomas exhibiting chondroid differentiation [10]. There was little mentioned about the presence of SOX9 or the intracellular location of the protein in normal breast epithelial cells.…”

“…Recently, a report by Kusafuka et al showed SOX9 to be present in 4 out of 4 cases of a subset of breast carcinomas that are metaplastic with cartilaginous features [10]. Metaplastic breast carcinoma is a rare tumor with a worse prognosis than typical breast cancer [11].…”

Matrix-Producing Carcinoma of the Breast: Case Report

“…In addition, partial immunopositivity for p63, a myoepithelial marker, was considered myoepithelial cell-like differentiation. They also demonstrated desmosome-like intercellular junctional structures, tonofilaments, and actin filaments in carcinoma cells ultrastructurally (7). Because the majority of MPC cases reported in the literature showed triple -negative features [estrogen receptor (−), progesterone receptor (−), and Her2/neu (−)] and a basal-like phenotype (cytokeratin 5/6, cytokeratin 14, and epidermal growth factor receptor positivity) (5,6,8,9), systemic chemotherapy following surgery is the treatment of choice at present (6).…”