Helsinki score—a novel model for prediction of metastases in adrenocortical carcinomas

Pennanen, Mirkka; Heiskanen, Ilkka; Sane, Timo; Remes, Satu Maria; Mustonen, Harri; Haglund, Caj; Arola, Johanna

doi:10.1016/j.humpath.2014.11.015

Cited by 84 publications

(122 citation statements)

References 20 publications

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“…The novel Helsinki score introduced by the authors2 was also determined. The Helsinki score includes 3 × mitotic rate (>5/50 high-power field)+5 × presence of necrosis + proliferation index (Ki67/mib-1).…”

Section: Methodsmentioning

confidence: 99%

“…Various histopathological criteria differentiate adrenocortical carcinomas from adenomas; the most common is the Weiss scoring system 1. Recently, we described the Helsinki score, a more objective and accurate tool to evaluate these tumours’ metastatic potential 2. Biomarkers reflecting the malignant potential of the tumour could further contribute to clinicopathological diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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C-myc expression in adrenocortical tumours

Pennanen¹,

Hagström

Heiskanen

et al. 2017

J Clin Pathol

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AimsWidespread use of high-resolution imaging techniques and thus increased prevalence of adrenal lesions has made diagnostics of adrenocortical tumours an increasingly important clinical issue. In non-metastatic tumours, diagnosis is based on histology. New or enhanced information for clinicopathological diagnosis, revealing the malignant potential of the tumour, could emerge by means of biomarkers. The connection of proto-oncogene c-myc to adrenocortical neoplasias is poorly known, although the Wnt/beta-catenin pathway, one of the signalling pathways leading to induction of c-myc expression, has been connected to development of adrenocortical neoplasias. We studied c-myc expression in adrenocortical tumours and investigated molecules associated with the signalling pathway of c-myc, including cell cycle-related proteins p27, cyclin E and cyclin D1.MethodsWe studied 195 consecutive adult patients with 197 primary adrenocortical tumours. Histopathological diagnosis was determined by Weiss score and the novel Helsinki score. C-myc, cyclin D1, cyclin E and p27 expressions were determined by immunohistochemistry.ResultsBenign adenomas showed prominent nuclear c-myc expression comparable to that of normal adrenocortical cells, whereas carcinomas showed increased cytoplasmic expression. Strong cytoplasmic and weak nuclear c-myc expressions associated with malignancy and adverse outcome. C-myc staining did not correlate with cyclin E. Cyclin D1 correlated with cytoplasmic c-myc expression and to a lesser extent with nuclear c-myc. P27 correlated with cytoplasmic c-myc, but not with nuclear c-myc. P27 correlated with cyclin E.ConclusionsStrong cytoplasmic c-myc expression and weak nuclear expression in adrenocortical tumours associated with malignancy and shorter survival.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C-myc expression in adrenocortical tumours

Pennanen¹,

Hagström

Heiskanen

et al. 2017

J Clin Pathol

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“…Different more simplified algorithms have been proposed with only the most reliable parameters included (Aubert et al 2002). Pennanen et al (2015) recently developed the Helsinki score, which consists of the sum of 3! mitotic rateC5!…”

Section: Current Tools To Diagnose Accsmentioning

confidence: 99%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

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Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

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“…For these reasons, a new scoring system (Helsinki score) was recently introduced, which is based on the combined evaluation of morphological parameters (necrosis and mitotic index >5/50 high-power fields) and of the Ki67 labeling index (LI) (see below). This system was shown to be able to predict the metastatic potential of ACC with very high sensitivity and specificity (Pennanen et al 2015). Another very recent study extended and confirmed the prognostic validity of the Helsinki score on a larger series of ACC cases (Duregon et al 2017).…”

Section: Histopathological Evaluation Of Malignancy In Act: Around Anmentioning

confidence: 81%

“…A recent large multicentric ENS@T study has shown that the KI67 LI is a very reliable parameter to predict disease recurrence (disease-free survival, DFS) and overall survival (OS) in ACC patients after complete tumor resection . Furthermore, Ki67 LI integration with morphological parameters in the newly introduced Helsinki score makes it to outperform the Weiss system as a prognostic indicator in ACC (see above) (Pennanen et al 2015, Duregon et al 2017. However, a limitation of the Ki67 LI consists in difficulties in its standardization and reproducibility when applied to many tumor types, including ACC (Papathomas et al 2016).…”

Section: Immunohistochemical Markers Improve Prognostic Assessment Inmentioning

confidence: 99%

The next step: mechanisms driving adrenocortical carcinoma metastasis

Lalli

Luconi²

2018

Endocrine-Related Cancer

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Endocrine tumors have the peculiarity to become clinically evident not only due to symptoms related to space occupation by the growing lesion, similarly to most other tumors, but also, and most often, because of their specific hormonal secretion, which significantly contributes to their pathological burden. Malignant endocrine tumors, in addition, have the ability to produce distant metastases. Here, we critically review the current knowledge about mechanisms and biomarkers characterizing the metastatic process in adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high risk of relapse and metastatization even when the primary tumor is diagnosed and surgically removed at an early stage. We highlight perspectives of future research in the domain and possible new therapeutic avenues based on targeting factors having an important role in the metastatic process of ACC.

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Helsinki score—a novel model for prediction of metastases in adrenocortical carcinomas

Cited by 84 publications

References 20 publications

C-myc expression in adrenocortical tumours

C-myc expression in adrenocortical tumours

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

The next step: mechanisms driving adrenocortical carcinoma metastasis

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