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Expression of Apocrine Differentiation Markers in Neuroendocrine Breast Carcinomas of Aged Women

Anna Sapino, Luisella Righi, Paola Cassoni, Mauro Papotti, Patrizia Gugliotta and Gianni Bussolati

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FIGURE 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

FIGURE 1.

Expression of ChA and GCDFP-15 in different histotypes of NE breast cancers (mucinous, solid papillary, and solid cohesive types). A cribriform sheet of cells is floating within the mucin lakes in a mucinous NE–apocrine carcinoma (A). The same tumor is positive for ChA (B) and GCDFP-15 (C) in >50% of cells. In a solid papillary carcinoma, a solid nest of cells (upper) is separated from a mucin-producing area by sclerotic stroma (D). ChA is expressed only in the mucinous component (E), whereas GCDFP-15 is expressed in both counterparts (F). Solid cohesive NE–apocrine carcinoma showing rosettelike structures and peripheral cell palisading are reminiscent of carcinoid tumors (G). Both ChA (H) and GCDFP-15 (I) are expressed.

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FIGURE 2.

Expression of ChA, ChB, GCDFP-15, and AR in different histotypes of NE breast cancers (solid cohesive, alveolar, and poorly differentiated types). Double immunostaining of a case of solid-cohesive carcinoma (immunoperoxidase and beta-galactosidase). ChA-positive NE cells are in brown, whereas apocrine-differentiated cells expressing GCDFP-15 are in blue (A). At higher magnification, the coexpression of ChA and GCDFP-15 in the same cells (arrows) is evident (B). Pure NE alveolar carcinoma featuring round alveolarlike structures, separated by scanty dense stroma, is formed by a homogeneous population of large clear cells, with faintly granular cytoplasm (C), positive for ChA (D). Poorly differentiated NE carcinoma shows clusters of cells, with moderate to abundant cytoplasm, nuclei with vesicular to finely granular chromatin, and high number of mitoses (E). Immunostaining for ChB shows an intense cytoplasmic granular staining (F). In a case of solid-cohesive spindle cell NE-apocrine carcinoma (G), the presence of specific mRNAs for ChA GCDFP-15 (nitroblue tetrazolium salt substrate) is demonstrated with in situ hybridization (H). The nuclei of the same tumor are intensely and diffusely positive for AR (I).

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FIGURE 3.

Kaplan-Meier curves of 35 patients. (A) Patients' survival is influenced by the histological type of tumors. The patients with mucinous and solid papillary carcinomas (producing some degree of mucin; a) have a significantly longer survival than patients with tumors of the other histological types (P = .05; b). (B) In short-term follow-up, the survival is not significantly modified by the immunophenotype (pure NE versus NE-apocrine tumors, P = .1), but 5 years after surgery, there is a tendency to a better prognosis for patients with NE-apocrine tumors. (C) The histological grade influenced prognosis; in fact, patients with G1 tumors are all alive at 13 years, those with G2 tumors have an intermediate prognosis; and all patients with G3 tumors had died by the 6-year follow-up. Patients with ER- (D) and PR- (E) tumors have significantly poorer prognosis than patients with ER+ and PR+ tumors.

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