title: Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis.
abstract: Adrenocortical carcinoma (ACC) is a rare, highly malignant neoplasm harboring marked histologic heterogeneity. The Ki-67 labeling index (LI) is one of the most effective diagnostic and prognostic markers in ACC. However, its assessment has by no means been standardized. Therefore, in this study, we analyzed the Ki-67 LI in 18 ACC cases both by seven pathologists using microscopes (MA; manual analysis) and with digital image analysis (DIA) and also compared the Ki-67 LI obtained by selecting "hot spots" and formulating the "average" reading of the whole tumor specimen. In addition, we performed statistical analysis of the association between Ki-67 LI and the clinical and pathologic features of individual cases. The DIA was significantly correlated with MA in hot spots but not in the average fields. The Ki-67 LI in hot spots was significantly and consistently higher than that in average areas by both MA and DIA, indicating intratumoral heterogeneity. The Ki-67 LI was significantly correlated with the Weiss criteria (eosinophilic cytoplasm, nuclear atypia, atypical mitoses, and sinusoidal invasion) by any mode of evaluation. The clinical outcome was significantly better in the patients with a Ki-67 < 10% than in those with a Ki-67 > 10% by MA in hot spots. The Ki-67 LI in hot spots measured by MA best reflected the clinical and pathologic features of ACC. Employment of DIA to obtain the Ki-67 LI in ACC requires further improvement, including correction of its overestimation of the value by counting non-tumorous cells and nuclear segmentation in areas of high cell density.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan. Electronic address: yasu-naka@patholo2.med.tohoku.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shibahara
authors.affiliation: Division of Pathology, Tohoku University Hospital, 980-8574, Sendai.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Konosu-Fukaya
authors.affiliation: Division of Pathology, Tohoku University Hospital, 980-8574, Sendai.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sato
authors.affiliation: Division of Pathology, Tohoku Rosai Hospital, Sendai.
authors.forename: Fumie
authors.initials: F
authors.lastname: Kubota-Nakayama
authors.affiliation: Department of Family and Community Medicine, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Shizuoka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oki
authors.affiliation: Department of Diagnostic Pathology, University Hospital Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Baba
authors.affiliation: Department of Radiation Health Management, Fukushima Medical University, Fukushima, 960-1295, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Midorikawa
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, 980-8575, Sendai.
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, 980-8575, Sendai.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018268:Adrenocortical Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D057205:Automation, Laboratory; D049109:Cell Proliferation; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007564:Japan; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D009367:Neoplasm Staging; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen
keywords: Adrenocortical carcinoma; Digital image analysis; Immunohistochemistry; Ki-67 labeling index; Weiss criteria