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Virchows Arch. 2017 Oct;471(4):521-530. doi: 10.1007/s00428-017-2215-y. Epub 2017 Aug 24.

Expression of neurotensin receptor 1 in endometrial adenocarcinoma is correlated with histological grade and clinical outcome.

Author information

1
Department of Medical Gynecology, CHRU de Nancy, Université de Lorraine, Vandœuvre-lès-Nancy, France.
2
INSERM U954, Université de Lorraine, Vandœuvre-lès-Nancy, France.
3
INSERM U1007, Université Paris Descartes, 45, Rue des Saints-Pères, 75006, Paris, France. patricia.forgez@inserm.fr.
4
Department of Pathology, CHRU de Nancy, Université de Lorraine, Nancy, France.
5
Centre de Ressources Biologiques, BB-0033-00035, CHRU de Nancy, Nancy, France.
6
Department of Radiotherapy, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France.
7
ESPRI-BioBase, Plateforme d'Aide à la Recherche Clinique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
8
Department of Gynecology and Obstetrics, CHRU de Nancy, Université de Lorraine, Nancy, France.
9
Department of Genetics, CHRU de Nancy, Université de Lorraine, Vandœuvre-lès-Nancy, France.
10
INSERM U1007, Université Paris Descartes, 45, Rue des Saints-Pères, 75006, Paris, France.
11
Université Paris Descartes, Department of Medical Gynecology, Hôpital Cochin Port-Royal, AP-HP, Paris, France.
12
INSERM U954, Université de Lorraine, Vandœuvre-lès-Nancy, France. g.gauchotte@chru-nancy.fr.
13
Department of Pathology, CHRU de Nancy, Université de Lorraine, Nancy, France. g.gauchotte@chru-nancy.fr.

Abstract

The promalignant effects of neurotensin (NTS) are sustained in many solid tumors, including hormone-dependent cancers. As the endometrium is also subjected to hormonal regulation, we evaluated the contribution of NTS to endometrial carcinogenesis. Neurotensin receptor 1 (NTSR1) expression and NTSR1 promoter methylation (HM450) were analyzed in 385 cases of endometrial carcinoma from The Cancer Genome Atlas (TCGA). Additionally, from a series of 100 endometrial carcinomas, and 66 benign endometrium samples, NTS and NTSR1 labeling was evaluated by immunohistochemistry. Using TCGA series, NTSR1 messenger RNA (mRNA) level was negatively correlated with overall survival (OS) and progression-free survival (PFS) (p = 0.0012 and p = 0.0116, respectively), and positively correlated with the grade (p = 0.0008). When including only endometrioid carcinomas, NTSR1 mRNA level continued to be negatively correlated with OS (log-rank: p < 0.0001) and PFS (log-rank: p = 0.002). A higher NTSR1 mRNA level was significantly associated with a loss of NTSR1 promoter methylation. Immunohistochemical expression of NTS and NTSR1 was significantly increased in adenocarcinoma (n = 100), as compared to benign endometrium (p < 0.001). NTSR1 expression was positively correlated with grade (p = 0.004). High immunohistochemical expression of cytoplasmic NTSR1 was significantly correlated with a shorter OS and PFS (p < 0.001 and p = 0.001, respectively). This correlation remained significant when excluding non-endometrioid subtypes (p = 0.04 and p = 0.02, respectively). In multivariate analysis, the expression of NTSR1 was an independent prognostic factor (p = 0.004). NTSR1 overexpression is a poor prognostic factor in endometrial cancer, highlighting the contribution of NTS in endometrial cancer progression and its uses as a prognostic marker, and as a potential therapeutic target.

KEYWORDS:

Cancer; Endometrial adenocarcinoma; Endometrium; NTSR1; Neurotensin

PMID:
28836043
DOI:
10.1007/s00428-017-2215-y
[Indexed for MEDLINE]

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