Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma

Silviu Sbiera; Iuliu Sbiera; Carmen Ruggiero; Mabrouka Doghman-Bouguerra; Esther Korpershoek; Ronald R. de Krijger; Hester Ettaieb; Harm Haak; Marco Volante; Mauro Papotti; Giuseppe Reimondo; Massimo Terzolo; Michaela Luconi; Gabriella Nesi; Massimo Mannelli; Rossella Libe; Bruno Ragazzon; Guillaume Assie; Jerome Bertherat; Barbara Altieri; Guido Fadda; Natalie Rogowski-Lehmann; Martin Reincke; Felix Beuschlein; Martin Fassnacht; Enzo Lalli

doi:10.1210/jc.2017-00984

Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma

Silviu Sbiera^*, Iuliu Sbiera, Carmen Ruggiero, Mabrouka Doghman-Bouguerra, Esther Korpershoek, Ronald R. de Krijger, Hester Ettaieb, Harm Haak, Marco Volante, Mauro Papotti, Giuseppe Reimondo, Massimo Terzolo, Michaela Luconi, Gabriella Nesi, Massimo Mannelli, Rossella Libe, Bruno Ragazzon, Guillaume Assie, Jerome Bertherat, Barbara AltieriGuido Fadda, Natalie Rogowski-Lehmann, Martin Reincke, Felix Beuschlein, Martin Fassnacht, Enzo Lalli^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has amajor 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%). 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.

Original language	English
Pages (from-to)	3491-3498
Number of pages	8
Journal	Journal of Clinical Endocrinology & Metabolism
Volume	102
Issue number	9
DOIs	https://doi.org/10.1210/jc.2017-00984
Publication status	Published - Sept 2017

Keywords

GENE-EXPRESSION
GENOMIC CHARACTERIZATION
HELSINKI SCORE
TUMORS
CANCER
PROLIFERATION
MARKER
CLASSIFICATION
VALIDATION
RECURRENCE

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Cite this

Sbiera, S., Sbiera, I., Ruggiero, C., Doghman-Bouguerra, M., Korpershoek, E., de Krijger, R. R., Ettaieb, H., Haak, H., Volante, M., Papotti, M., Reimondo, G., Terzolo, M., Luconi, M., Nesi, G., Mannelli, M., Libe, R., Ragazzon, B., Assie, G., Bertherat, J., ... Lalli, E. (2017). Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma. Journal of Clinical Endocrinology & Metabolism, 102(9), 3491-3498. https://doi.org/10.1210/jc.2017-00984

@article{af80760218a44ba48d5d285a95c0d751,

title = "Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma",

abstract = "Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has amajor 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%). 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.",

keywords = "GENE-EXPRESSION, GENOMIC CHARACTERIZATION, HELSINKI SCORE, TUMORS, CANCER, PROLIFERATION, MARKER, CLASSIFICATION, VALIDATION, RECURRENCE",

author = "Silviu Sbiera and Iuliu Sbiera and Carmen Ruggiero and Mabrouka Doghman-Bouguerra and Esther Korpershoek and {de Krijger}, {Ronald R.} and Hester Ettaieb and Harm Haak and Marco Volante and Mauro Papotti and Giuseppe Reimondo and Massimo Terzolo and Michaela Luconi and Gabriella Nesi and Massimo Mannelli and Rossella Libe and Bruno Ragazzon and Guillaume Assie and Jerome Bertherat and Barbara Altieri and Guido Fadda and Natalie Rogowski-Lehmann and Martin Reincke and Felix Beuschlein and Martin Fassnacht and Enzo Lalli",

year = "2017",

month = sep,

doi = "10.1210/jc.2017-00984",

language = "English",

volume = "102",

pages = "3491--3498",

journal = "Journal of Clinical Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "9",

}

Sbiera, S, Sbiera, I, Ruggiero, C, Doghman-Bouguerra, M, Korpershoek, E, de Krijger, RR, Ettaieb, H, Haak, H, Volante, M, Papotti, M, Reimondo, G, Terzolo, M, Luconi, M, Nesi, G, Mannelli, M, Libe, R, Ragazzon, B, Assie, G, Bertherat, J, Altieri, B, Fadda, G, Rogowski-Lehmann, N, Reincke, M, Beuschlein, F, Fassnacht, M & Lalli, E 2017, 'Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma', Journal of Clinical Endocrinology & Metabolism, vol. 102, no. 9, pp. 3491-3498. https://doi.org/10.1210/jc.2017-00984

TY - JOUR

T1 - Assessment of VAV2 Expression Refines Prognostic Prediction in Adrenocortical Carcinoma

AU - Sbiera, Silviu

AU - Sbiera, Iuliu

AU - Ruggiero, Carmen

AU - Doghman-Bouguerra, Mabrouka

AU - Korpershoek, Esther

AU - de Krijger, Ronald R.

AU - Ettaieb, Hester

AU - Haak, Harm

AU - Volante, Marco

AU - Papotti, Mauro

AU - Reimondo, Giuseppe

AU - Terzolo, Massimo

AU - Luconi, Michaela

AU - Nesi, Gabriella

AU - Mannelli, Massimo

AU - Libe, Rossella

AU - Ragazzon, Bruno

AU - Assie, Guillaume

AU - Bertherat, Jerome

AU - Altieri, Barbara

AU - Fadda, Guido

AU - Rogowski-Lehmann, Natalie

AU - Reincke, Martin

AU - Beuschlein, Felix

AU - Fassnacht, Martin

AU - Lalli, Enzo

PY - 2017/9

Y1 - 2017/9

N2 - Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has amajor 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%). 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.

AB - Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with overall poor prognosis. The Ki67 labeling index (LI) has amajor 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%). 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.

KW - GENE-EXPRESSION

KW - GENOMIC CHARACTERIZATION

KW - HELSINKI SCORE

KW - TUMORS

KW - CANCER

KW - PROLIFERATION

KW - MARKER

KW - CLASSIFICATION

KW - VALIDATION

KW - RECURRENCE

U2 - 10.1210/jc.2017-00984

DO - 10.1210/jc.2017-00984

M3 - Article

C2 - 28911143

SN - 0021-972X

VL - 102

SP - 3491

EP - 3498

JO - Journal of Clinical Endocrinology & Metabolism

JF - Journal of Clinical Endocrinology & Metabolism

IS - 9

ER -