title: Achaete-scute homolog 1 as a marker of poorly differentiated neuroendocrine carcinomas of different sites: a validation study using immunohistochemistry and quantitative real-time polymerase chain reaction on 335 cases.
abstract: Neuroendocrine carcinomas show overlapping morphological and immunohistochemical features independently of their site of origin, which makes identification of the primary location problematic when they are diagnosed as metastases of unknown origin. Neuroendocrine carcinomas are easily morphologically differentiated from neuroendocrine tumors in surgical material, although this distinction can be difficult when using small biopsy specimens. The diagnostic usefulness of different transcription factors as site-specific markers or as discriminating markers between neuroendocrine carcinomas and neuroendocrine tumors has been previously studied with sometimes contradictory results. In this respect, the role of achaete-scute homolog 1 has been poorly investigated, although some recent findings demonstrate its expression in neuroendocrine carcinomas. Using immunohistochemistry and quantitative real-time polymerase chain reaction, we investigated the expression of achaete-scute homolog 1 in 335 neuroendocrine neoplasms (194 neuroendocrine carcinomas and 141 neuroendocrine tumors) of different sites, to check its possible utility as diagnostic marker. High concordance between immunohistochemical and molecular findings was found. Achaete-scute homolog 1 expression was identified in 82% of lung neuroendocrine carcinomas and 70% of extrapulmonary neuroendocrine carcinomas. Achaete-scute homolog 1 was not detected in any gastroenteropancreatic neuroendocrine tumor and was found in only a minority of lung carcinoids. The diagnostic sensitivity and specificity of achaete-scute homolog 1 expression were 82.4% and 89.7% in distinguishing neuroendocrine carcinomas from neuroendocrine tumors of the lung, 40.6% and 100% to differentiate extrapulmonary neuroendocrine carcinomas from neuroendocrine tumors, and 82.4% and 59.4% in distinguishing lung from extrapulmonary neuroendocrine carcinomas. Our data suggest that achaete-scute homolog 1 is not a site-specific marker. However, achaete-scute homolog 1 may be proposed as a diagnostic marker of poor differentiation and may help to differentiate neuroendocrine carcinomas from neuroendocrine tumors in difficult cases.
authors: Department of Pathology, Ospedale di Circolo, 21100 Varese, Italy. stefano.larosa@ospedale.varese.it
authors: Stefano
authors: S
authors: La Rosa
authors: Alessandro
authors: A
authors: Marando
authors: Gaia
authors: G
authors: Gatti
authors: Ida
authors: I
authors: Rapa
authors: Marco
authors: M
authors: Volante
authors: Mauro
authors: M
authors: Papotti
authors: Fausto
authors: F
authors: Sessa
authors: Carlo
authors: C
authors: Capella
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; C065500:ASCL1 protein, human