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J Clin Endocrinol Metab. 2017 Sep 1;102(9):3491-3498. doi: 10.1210/jc.2017-00984.

Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma.

Author information

1
Department of Internal Medicine I - Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, 97080 Wurzburg, Germany.
2
Université Côte d'Azur, Sophia Antipolis, 06560 Valbonne, France.
3
CNRS UMR7275, Sophia Antipolis, 06560 Valbonne, France.
4
NEOGENEX CNRS International Associated Laboratory, Sophia Antipolis, 06560 Valbonne, France.
5
Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, 06560 Valbonne, France.
6
Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, 3000 CA Rotterdam, The Netherlands.
7
Department of Pathology, Reinier de Graaf Hospital, 2625 AD Delft, The Netherlands.
8
Department of Internal Medicine, Máxima Medical Centre, 5631 BM Eindhoven/Veldhoven, The Netherlands.
9
Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre+, 6202 AZ Maastricht, The Netherlands.
10
Maastricht University, CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, 6200 MD Maastricht, The Netherlands.
11
Department of Oncology, University of Turin at San Luigi Hospital, 10043 Orbassano, Italy.
12
Department of Clinical and Biological Sciences, University of Turin at San Luigi Hospital, 10043 Orbassano, Italy.
13
Department of Experimental and Clinical Biomedical Sciences "Mario Serio," University of Florence, 50139 Florence, Italy.
14
Inserm U1016, Institut Cochin, 75014 Paris, France.
15
CNRS UMR8104, 75014 Paris, France.
16
Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
17
Division of Endocrinology and Metabolic Diseases, Catholic University of the Sacred Heart, 00168 Rome, Italy.
18
Division of Anatomic Pathology and Histology, Catholic University of the Sacred Heart, 00168 Rome, Italy.
19
Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
20
Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, 8091 Zurich, Switzerland.
21
Comprehensive Cancer Center Mainfranken, University of Würzburg, 97080 Wurzburg, Germany.

Abstract

Context:

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has a major prognostic role in localized ACC after complete resection, but its estimates may suffer from considerable intra- and interobserver variability. VAV2 overexpression induced by increased Steroidogenic Factor-1 dosage is an essential factor driving ACC tumor cell invasion.

Objective:

To assess the prognostic role of VAV2 expression in ACC by investigation of a large cohort of patients.

Design, Setting, and Participants:

A total of 171 ACC cases (157 primary tumors, six local recurrences, eight metastases) from seven European Network for the Study of Adrenal Tumors centers were studied.

Outcome Measurements:

H-scores were generated to quantify VAV2 expression. VAV2 expression was divided into two categories: low (H-score, <2) and high (H-score, ≥2). The Ki67 LI retrieved from patients' pathology records was also categorized into low (<20%) and high (≥20%). Clinical and immunohistochemical markers were correlated with progression-free survival (PFS) and overall survival (OS).

Results:

VAV2 expression and Ki67 LI were significantly correlated with each other and with PFS and OS. Heterogeneity of VAV2 expression inside the same tumor was very low. Combined assessment of VAV2 expression and Ki67 LI improved patient stratification to low-risk and high-risk groups.

Conclusion:

Combined assessment of Ki67 LI and VAV2 expression improves prognostic prediction in ACC.

PMID:
28911143
DOI:
10.1210/jc.2017-00984
[Indexed for MEDLINE]

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