title: Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma.
abstract: Mitotic count on hematoxylin and eosin slides is a fundamental morphological criterion in the diagnosis and grading of adrenocortical carcinoma in any scoring system employed. Moreover, it is the unique term strongly associated with patient's prognosis. Phospho-histone H3 is a mitosis-specific antibody, which was already proven to facilitate mitotic count in melanoma and other tumors. Therefore, a study was designed to assess the diagnostic and prognostic role of phospho-histone H3 in 52 adrenocortical carcinomas, comparing manual and computerized count to standard manual hematoxylin- and eosin-based method and Ki-67 index. Manual hematoxylin and eosin and phospho-histone H3 mitotic counts were highly correlated (r=0.9077, P<0.0001), better than computer-assisted phospho-histone H3 evaluations, and had an excellent inter-observer reproducibility at Bland-Altman analysis. Three of 15 cases having <5 mitotic figures per 50 high-power fields by standard count on hematoxylin and eosin gained the mitotic figure point of Weiss Score after a manual count on phospho-histone H3 slides. Traditional mitotic count confirmed to be a strong predictor of overall survival (P=0.0043), better than phospho-histone H3-based evaluation (P=0.051), but not as strong as the Ki-67 index (P<0.0001). The latter further segregated adrenocortical carcinomas into three prognostic groups, stratifying cases by low (<20%), intermediate (20-50%), and high (>50%) Ki-67 values. We conclude that (a) phospho-histone H3 staining is a useful diagnostic complementary tool to standard hematoxylin and eosin mitotic count, enabling optimal mitotic figure evaluation (including atypical mitotic figures) even in adrenocortical carcinomas with a low mitotic index and with a very high reproducibility; (b) Ki-67 proved to be the best prognostic indicator of overall survival, being superior to the mitotic index, irrespective of the method (standard on hematoxylin and eosin or phospho-histone H3-based) used to count mitotic figures.
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Duregon
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Molinaro
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.affiliation: Department of Statistics, University of Padua, Padova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ventura
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, Italy.
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bolla
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin at San Luigi Hospital, Orbassano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.affiliation: Department of Oncology, University of Turin at San Luigi Hospital, Orbassano, Italy.
authors.forename: Mauro G
authors.initials: MG
authors.lastname: Papotti
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D004801:Eosine Yellowish-(YS); D005260:Female; D006416:Hematoxylin; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D010766:Phosphorylation; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D006657:Histones; D019394:Ki-67 Antigen; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin