title: Neuroendocrine differentiation in breast carcinoma: clinicopathological features and outcome.
abstract: OBJECTIVE
  Primary neuroendocrine (NE) breast carcinoma (BC) is an entity with a wide range of prevalence and poorly defined clinical behaviour. We evaluated the prevalence, clinicopathological features and clinical outcome of NEBC.
  
  
  RESULTS
  Immunohistochemical staining for synaptophysin and chromogranin A was performed on whole sections from 1232 consecutive cases of invasive BC. We divided NEBC into focal (10-49% positive cells) and diffuse (≥50% positive cells) and compared the outcome of patients with NEBC with strictly matched non-NEBC. A total of 128 BC showed NE differentiation (10.4%): 84 diffuse (6.8%) and 44 focal (3.6%). NE differentiation showed a significant association with T4 stage (P = 0.001), solid-papillary and mucinous histotype (P < 0.0001), G2 grading (P = 0.002), positive oestrogen receptor (ER) (P = 0.003) and progesterone receptor (PR) (P = 0.002). Almost 90% of NEBC were ER(+) /HER2(-) and more than half ER(+) /HER2(-) /Ki67≥14%. Kaplan-Meier analysis revealed that patients with NEBC showed worse disease-free survival (DFS) (P = 0.04) compared to matched non-NEBC. We did not find significant differences regarding clinicopathological features, DFS and CSS between diffuse and focal neuroendocrine BC.
  
  
  CONCLUSIONS
  This study demonstrates that NEBC represents 7-10% of invasive BC and that NE differentiation does not affect the prognosis of BC in terms of CSS.
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bogina
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.|Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bortesi
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Marconi
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sommaggio
authors.affiliation: Department of Oncology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Lunardi
authors.affiliation: Department of Oncology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.affiliation: Department of Surgery, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Massocco
authors.affiliation: Department of Oncology, ULSS 5 Ovest Vicentino, Vicenza, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Pegoraro
authors.affiliation: Department of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism / Q000473:pathology*; D053379:Chromogranin A / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016708:Synaptophysin
keywords: breast; cancer; neuroendocrine; outcome