title: Pleomorphic carcinomas of the lung show a selective distribution of gene products involved in cell differentiation, cell cycle control, tumor growth, and tumor cell motility: a clinicopathologic and immunohistochemical study of 31 cases.
abstract: We investigated 31 cases of pleomorphic carcinomas of the lung, with a double component of neoplastic epithelial cells and of spindle and/or giant cells. To correlate the morphologic diversity of these two cell components with their immunophenotype, we evaluated the expression of several gene products involved in cell differentiation (cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, vimentin, S-100 protein, smooth muscle actin, desmin), cell cycle control and apoptosis (p53, p21Waf1, p27Kip1, FHIT), tumor growth (proliferative fraction, assessed by Ki-67 antigen, and microvascular density, assessed by CD34 immunostaining), and tumor cell motility (fascin). We found the epithelial component to be significantly more immunoreactive for cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, cell cycle inhibitors p21Waf1, p27Kip1 and tumor suppressor gene FHIT, whereas the sarcomatoid component, independent of tumor stage and size, was more immunoreactive for vimentin, fascin, and microvascular density. Accordingly, we suggest a model of tumorigenesis whereby the mesenchymal phenotype of pleomorphic cells is likely induced by the selective activation and segregation of several molecules involved in cell differentiation, cell cycle control, and tumor cell growth and motility. Whether pleomorphic carcinomas of the lung are tumors with a dismal prognosis still remains an unsettled issue. In our series, however, stage I pleomorphic carcinomas have the same clinical behavior as ordinary non-small cell lung cancer, and only a high proliferative index (Ki-67 labeling index >35%) is associated with a worse prognosis in these tumors.
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute of European Oncology and University of Milan School of Medicine, Italy. giuseppe.pelosi@ieo.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
authors.forename: Filippo
authors.initials: F
authors.lastname: Fraggetta
authors.forename: Oscar
authors.initials: O
authors.lastname: Nappi
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Felice
authors.initials: F
authors.lastname: Pasini
authors.forename: Antonio
authors.initials: A
authors.lastname: Iannucci
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Solli
authors.forename: Hossein S
authors.initials: HS
authors.lastname: Musavinasab
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Manzoni
authors.forename: Alberto
authors.initials: A
authors.lastname: Terzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor