title: hASH1 is a specific immunohistochemical marker for lung neuroendocrine tumors.
abstract: Mammalian/human achaete-scute homolog 1 (hASH1) regulates neuroendocrine cell development. No detailed comparative study has been conducted to explore the immunohistochemical utility of hASH1 in distinguishing different types of lung cancers. We investigated the expression of hASH1, synaptophysin, chromogranin, and CD56 in 101 squamous cell carcinomas (SCCs), 183 adenocarcinomas (ADCs), 37 typical carcinoids (TCs), 14 atypical carcinoids (ACs), 11 large cell neuroendocrine carcinomas (LCNECs), and 24 small cell lung carcinomas (SCLCs) of the lung by immunohistochemical staining with a monoclonal antibody against hASH1. Staining intensity was graded from 0 to 3, and percentage of tumor cells in each grade was estimated. All cases of ADC and SCC were discreetly negative for hASH1 in contrast to their low percentage positivity for synaptophysin, chromogranin, and CD56. hASH1 positively stained TC (64.9%), AC (64.3%), LCNEC (72.7%), and SCLC (79.2%) as did chromogranin (TC, 100%; AC, 78.6%; LCNEC, 9.0%; and SCLC, 4.2%), synaptophysin (TC, 100%; AC, 78.6%; LCNEC, 81.8%; and SCLC, 83.3%), and CD56 (TC, 59.5%; AC, 57.1%; LCNEC, 36.4%; and SCLC, 79.2%). TC and AC often showed weaker intensity and lower percentage of tumor cells positive for hASH1 (median score, 5) than LCNEC and SCLC (median score, 40 and 170, respectively). There were statistically significant differences in mean intensity scores between SCLC (148.8 ± 20.1) and other neuroendocrine tumors: TC (37.1 ± 9.2) and AC (28.6 ± 10.8) or LCNEC (51.8 ± 18.0). Our findings indicate that hASH1 is a specific marker to distinguish neuroendocrine tumors from SCC and ADC. Additionally, hASH1 is a useful diagnostic marker for segregating SCLC from other neuroendocrine tumors.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642; Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardio vascular Research Center, Minneapolis, MN 55455.
authors.forename: Bo
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Cappel
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Findeis-Hosey
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Loralee
authors.initials: L
authors.lastname: McMahon
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Guang-Qian
authors.initials: GQ
authors.lastname: Xiao
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095.
authors.forename: Haodong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642; Department of Laboratory Medicine and Pathology, University of Minnesota, Dwan Variety Club Cardio vascular Research Center, Minneapolis, MN 55455. Electronic address: lif@umn.edu.
authors.forename: Faqian
authors.initials: F
authors.lastname: Li
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; C065500:ASCL1 protein, human
keywords: Achaete-scute homolog 1; Carcinoid; Large cell neuroendocrine carcinoma; Lung; Neuroendocrine tumors; Small cell lung carcinoma; hASH1