Immunohistochemistry of a Proliferation Marker Ki67/MIB1 in Adrenocortical Carcinomas: Ki67/MIB1 Labeling Index Is a Predictor for Recurrence of Adrenocortical Carcinomas

Morimoto, Ryo; Satoh, Fumitoshi; Murakami, Osamu; Suzuki, Takashi; Abe, Takaaki; Tanemoto, Masayuki; Abe, Michiaki; Uruno, Akira; Ishidoya, Shigeto; Arai, Yoichi; Takahashi, Kazuhiro; Sasano, Hironobu; Ito, Sadayoshi

doi:10.1507/endocrj.k07-079

Cited by 125 publications

(90 citation statements)

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“…The immunohistochemical assessment of cell proliferation by the analysis of cell cycle-associated antigens, such as MIB-1 (Ki-67) helps in determining the biology of the tumour. A high Ki-67 index is associated with shortened disease-free and overall survival [25,26]. Ki-67 index was not performed in our series, but mitotic index was.…”

Section: Discussionmentioning

confidence: 75%

Adrenocortical Carcinoma - A 25 Years Tertiary Centre Experience and Short Review of the Literature

Nunes¹

2018

EMIJ

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We performed an informatics search of the medical registers of our centre (filtered by age -over 18-years-old) for the diagnosis codes 'adrenal neoplasia' and 'adrenocortical carcinoma', and Review ArticleEndocrinol Metab Int J 2018, 6(1): 00148 AbstractPurpose: Adrenocortical carcinoma (ACC) is an uncommon and aggressive malignancy. We aimed to investigate the clinical and pathological findings of ACC diagnosed/treated in our hospital from January/1988 to January/2013.Methods: Analysis of presentation, imagiology, histopathology review, staging and survival data. Results:We reviewed 31 patients. The average age at diagnosis was 54.6±12.6years and 51.6% were females. At diagnosis, 11.8% were asymptomatic, 23.5% presented back pain, 17.6% general malaise, 9.4% hypercortisolism and 17.6% hirsutism/virilization. Tumours had 11.7±6.6cm, 53.3% located on the right side, 72.7% with local invasion, 25% inferior vena cava invasion and 63.7% distant metastasis. Ten were submitted to adrenalectomy: 80% presented atypical mitosis, 20% diffuse architecture, 60% ≤25% clear cells, 90% necrosis, 70% venous invasion, 90% sinusoidal invasion, 60% capsule invasion, mitotic index 41.2/50HPF (±36.8). One patient was treated with adjuvant radiotherapy, three with cytotoxic therapy and five with adrenolytic treatment (the remaining didn't start mitotane due to death or difficulties in obtaining the drug). Two patients, on stage II ENSAT, maintain follow up with mitotane and no evidence of recurrence. The mean overall survival was 59.2±52.4 months for stages I+II and 6.2±6.8 months for stages III+IV (ENSAT) (p=0.004). Conclusion:Our series reinforces the importance of early diagnosis by demonstrating a worse prognosis in more advanced stages and the need for a multidisciplinary approach from a team of experts in the management of such a rare malignancy.

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Section: Discussionmentioning

confidence: 75%

Adrenocortical Carcinoma - A 25 Years Tertiary Centre Experience and Short Review of the Literature

Nunes¹

2018

EMIJ

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“…A proliferation index over 5% has only been observed in ACC [27], but ACC with low proliferation index can exist, parallel to those observed in adrenocortical adenoma (ACA) [27,29,37]. Some papers [29,39] reported that a high level of Ki-67 seems to correlate with a shortness disease survival and maybe useful as a marker of worse prognosis. However, at present for adrenocortical neoplasms, variability in Ki-67 staining procedure and evaluation might be responsible for poor standardization and applicability of this marker as a diagnostic tool, and detailed recommendation is therefore needed.…”

Section: Ki-67 Proliferation Indexmentioning

confidence: 95%

The Weiss Score and Beyond—Histopathology for Adrenocortical Carcinoma

et al. 2011

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The pathological diagnosis of adrenocortical carcinoma (ACC) is still challenging for its rarity and the presence of special variants (pediatric, oncocytic, myxoid, and sarcomatoid). It is based on the recognition at light microscopy of at least three among nine morphological parameters, according to the Weiss scoring system, which has been introduced 27 years ago and nowadays is the most widely employed. Nevertheless, the diagnostic performance of this system is very high but does not reach a sensitivity and specificity of 100%, its diagnostic applicability is potentially low among non-expert pathologists, and a group of borderline cases with only one or two criteria exist of uncertain behavior. Moreover, it is scarcely reproducible in the ACC morphological variants. In fact, specifically for the pure oncocytic neoplasms that seem to have a better prognosis in comparison to the conventional ACCs, a modified system (the Lin-Weiss-Bisceglia) has been proposed. With the aim to simplify the ACC diagnosis, 2 years ago, the "reticulin" diagnostic algorithm has been proposed, based on the observation that the tumoral reticulin framework (highlighted by reticulin silver-based histochemical staining) is consistently disrupted in malignant cases but only in a small subset of benign cases. Following this algorithm, in the presence of reticulin alterations, malignancy is further defined through the identification of at least one of the following parameters: necrosis, high mitotic rate, and venous invasion. As a complement to the morphological approach, some immunohistochemical markers (such as steroidogenic factor 1) have been proposed as diagnostic and prognostic adjuncts but still lack wide clinical validation.

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“…41 The Ki-67 index represents an alternative method for assessing the proliferative potential in adrenocortical tumors and has already been shown to differentiate adrenocortical adenoma from carcinoma, [42][43][44][45][46][47][48][49] and to predict tumor behavior. 42,50,51 However, the use of the Ki-67 index is not officially incorporated in the diagnostic work up of adrenocortical carcinoma, which still largely relies on histomorphological parameters. 52 On the basis of the foregoing, our study was designed on a relatively large series of 52 adrenocortical carcinomas to assess the diagnostic and prognostic roles of phospho-histone H3 immunostaining in comparison with both manual and computer-assisted hematoxylin and eosin mitotic count and Ki-67 index determination.…”

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confidence: 99%

Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma

et al. 2014

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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 ¼ 0.9077, Po0.0001), better than computer-assisted phospho-histone H3 evaluations, and had an excellent inter-observer reproducibility at Bland-Altman analysis. Three of 15 cases having o5 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 ¼ 0.0043), better than phospho-histone H3-based evaluation (P ¼ 0.051), but not as strong as the Ki-67 index (Po0.0001). The latter further segregated adrenocortical carcinomas into three prognostic groups, stratifying cases by low (o20%), intermediate (20-50%), and high (450%) Ki-67 values. We conclude that (a) phosphohistone 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.

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Immunohistochemistry of a Proliferation Marker Ki67/MIB1 in Adrenocortical Carcinomas: Ki67/MIB1 Labeling Index Is a Predictor for Recurrence of Adrenocortical Carcinomas

Cited by 125 publications

References 17 publications

Adrenocortical Carcinoma - A 25 Years Tertiary Centre Experience and Short Review of the Literature

Adrenocortical Carcinoma - A 25 Years Tertiary Centre Experience and Short Review of the Literature

The Weiss Score and Beyond—Histopathology for Adrenocortical Carcinoma

Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma

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