title: Promyelocytic leukemia zinc finger and histone H1.5 differentially stain low- and high-grade pulmonary neuroendocrine tumors: a pilot immunohistochemical study.
abstract: Promyelocytic leukemia zinc finger is a zinc finger transcription factor that functions as a transcriptional repressor. Its expression has been shown to be down-regulated in hematopoietic, melanocytic, and mesothelial malignancies. Histone H1.5 is a variant of histone H1, a family of linker proteins that organizes chromosomes into higher order structures. Its function is of key importance in gene expression and has been linked to more aggressive forms of prostatic carcinoma. This study aimed to investigate the immunohistochemical detectability of promyelocytic leukemia zinc finger and histone H1.5 in pulmonary neuroendocrine tumors, comprising 11 carcinoid tumorlets, 24 typical carcinoids, 12 atypical carcinoids, 20 small cell carcinomas, 11 large cell neuroendocrine carcinomas, and 2 combined small cell carcinomas-large cell neuroendocrine carcinomas. Promyelocytic leukemia zinc finger immunohistochemistry revealed moderate or strong nuclear staining in all carcinoid tumorlets, 23 of 24 typical carcinoids, and 7 of 12 atypical carcinoids in contrast to 9 of 11 large cell neuroendocrine carcinomas, all small cell carcinoma, and both combined small cell carcinoma-large cell neuroendocrine carcinomas, which showed no nuclear immunoreactivity. Histone H1.5 immunohistochemistry revealed only focal or no immunoreactivity in all carcinoid tumorlets and 19 of 24 typical carcinoids, whereas 7 of 12 atypical carcinoids, 19 of 20 small cell carcinomas, 10 of 11 large cell neuroendocrine carcinomas, and both combined small cell carcinomas-large cell neuroendocrine carcinomas displayed positive (≥ 10%) nuclear immunoreactivity-ranging from a minority of weak staining to a majority of strong staining cases. Our data suggest that the relative expression ratios of promyelocytic leukemia zinc finger and histone H1.5 may correlate with grade of pulmonary neuroendocrine tumors. Immunohistochemical stains for these markers, especially on small biopsies with crush artifact, may prove to be diagnostically useful.
authors: Department of Pathology, Mount Sinai School of Medicine and Medical Center, New York, NY 10029, USA. jaclyn.hechtman@mountsinai.org
authors: Jaclyn Frances
authors: JF
authors: Hechtman
authors: Mary Beth
authors: MB
authors: Beasley
authors: Yayoi
authors: Y
authors: Kinoshita
authors: Huaibin Mabel
authors: HM
authors: Ko
authors: Ke
authors: K
authors: Hao
authors: David E
authors: DE
authors: Burstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D010865:Pilot Projects; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C104345:H1-5 protein, human; D006657:Histones; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C092037:ZBTB16 protein, human