title: Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma.
abstract: The American Association for the Study of Liver Diseases guidelines recommend the use of all available markers for improving the accuracy of the diagnosis of small hepatocellular carcinoma (HCC). To determine whether clathrin heavy chain (CHC), a novel HCC marker, is effective in combination with glypican 3 (GPC3), heat shock protein 70, and glutamine synthetase, we compared the performances of a three-marker panel (without CHC) and a four-marker panel (with CHC) in a series of small HCCs (≤2 cm) and nonsmall HCCs by core biopsy with a 20- to 21-gauge needle. The series included 39 nonsmall HCCs and 47 small HCCs (86 in all); the latter showed a well-differentiated histology [small grade 1 (G1)] in 30 cases (63.8%). The panel specificity was analyzed with the adjacent/extranodular cirrhotic liver (n = 30) and low-grade (n = 15) and high-grade dysplastic nodules (n = 16) as a control group. Absolute specificity (100%) for HCC was obtained only when at least two of the markers were positive (which two markers were positive did not matter). The addition of CHC to the panel increased the diagnostic accuracy for small HCCs (from 76.9% to 84.3%), and there was an important gain in sensitivity (from 46.8% to 63.8%). The four-marker panel had lower rates of accuracy (67.4%) and sensitivity (50%) for small G1 HCCs versus nonsmall G1 HCCs (93.9% and 88.2%, respectively). In seven cases (including six small G1 HCCs), there was no staining with any of the markers. Cirrhotic control livers were stained for CHC in four cases (13.3%) and for GPC3 in one case (3.3%).
  
  
  CONCLUSIONS
  The addition of CHC to the panel supports the diagnosis of small HCCs in challenging nodules on thin core biopsy samples. Small G1 HCCs include a group of earlier tumors characterized by a more silent phenotype and the progressive acquisition of the markers under study. The search for additional markers for early HCC diagnosis is warranted.
authors.affiliation: Department of Pathology, Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Di Tommaso
authors.forename: Annarita
authors.initials: A
authors.lastname: Destro
authors.forename: Valentina
authors.initials: V
authors.lastname: Fabbris
authors.forename: Gaia
authors.initials: G
authors.lastname: Spagnuolo
authors.forename: Anna
authors.initials: A
authors.lastname: Laura Fracanzani
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
authors.forename: Marco
authors.initials: M
authors.lastname: Maggioni
authors.forename: Carlo
authors.initials: C
authors.lastname: Patriarca
authors.forename: Roberto
authors.initials: R
authors.lastname: Maria Macchi
authors.forename: Michela
authors.initials: M
authors.lastname: Quagliuolo
authors.forename: Mauro
authors.initials: M
authors.lastname: Borzio
authors.forename: Massimo
authors.initials: M
authors.lastname: Iavarone
authors.forename: Angelo
authors.initials: A
authors.lastname: Sangiovanni
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000473:pathology*; D033922:Clathrin Heavy Chains / Q000032:analysis*; D004396:Coloring Agents; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D004396:Coloring Agents; D033922:Clathrin Heavy Chains