Nestin as a Diagnostic and Prognostic Marker for Combined Hepatocellular-Cholangiocarcinoma.
(1)
,
(2)
,
(3)
,
(4)
,
(5)
,
,
(6, 7)
,
,
(8)
,
,
(9, 10)
,
,
,
,
,
(11)
,
(12, 11)
,
(13)
,
,
,
,
,
,
(14)
,
,
,
(15)
,
(16)
,
(17, 18)
,
(17, 18)
,
(19)
,
(9)
,
(20)
,
(21)
,
,
(22)
,
,
(23)
,
(24, 25)
,
(26)
,
(27, 28)
,
(29)
,
(29)
,
(17)
,
(30, 31)
,
(32)
,
(7, 33)
,
,
,
,
,
(18)
,
(34)
,
(35)
,
,
,
(36)
,
(37, 38, 39, 40)
,
(41)
,
(18, 17)
,
(17)
,
,
(42)
,
,
(43)
,
(44)
,
(45)
,
,
,
(46, 47)
,
(48, 9)
,
,
(49, 50)
,
(51)
,
,
(49, 52)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
Lara Heij
- Fonction : Auteur
Rondell P. Graham
- Fonction : Auteur
Suzanne Chartier
- Fonction : Auteur
Mukul Vij
- Fonction : Auteur
Daniela Allende
- Fonction : Auteur
Alba Diaz
- Fonction : Auteur
Carla Fuster
- Fonction : Auteur
Katja Evert
- Fonction : Auteur
Diego Francesco Calvisi
- Fonction : Auteur
Wei Qiang Leow
- Fonction : Auteur
Howard Ho Wai Leung
- Fonction : Auteur
Jan Bednarsch
- Fonction : Auteur
Mohamed Rela
- Fonction : Auteur
Anthony Wing-Hung Chan
- Fonction : Auteur
Lukas Otero Sanchez
- Fonction : Auteur
Denis Chatelain
- Fonction : Auteur
- PersonId : 1149906
- IdRef : 080482635
Myriam Remmelink
- Fonction : Auteur
Emmanuelle Kempf
- Fonction : Auteur
- PersonId : 752391
- IdHAL : emmanuelle-kempf
- ORCID : 0000-0002-9285-1966
Sophie Michalak-Provost
- Fonction : Auteur
Jakob Nikolas Kather
- Fonction : Auteur
Annette S. H. Gouw
- Fonction : Auteur
Purva Gopal
- Fonction : Auteur
Raffaele Brustia
- Fonction : Auteur
- PersonId : 177701
- IdHAL : raffaele-brustia
- ORCID : 0000-0001-6426-9533
- IdRef : 267306601
Darius F. Rüther
- Fonction : Auteur
Sören A. Weidemann
- Fonction : Auteur
Eleonora De Martin
- Fonction : Auteur
Pooja Navale
- Fonction : Auteur
Regina Cheuk-Lam Lo
- Fonction : Auteur
Mylène Sebbagh
- Fonction : Auteur
Marie Lequoy
- Fonction : Auteur
- PersonId : 1222955
- IdHAL : marie-lequoy
- ORCID : 0000-0001-8836-3487
Mina Komuta
- Fonction : Auteur
Jeanne Shen
- Fonction : Auteur
Résumé
BACKGROUND AND AIMS: Combined Hepatocellular-Cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLC. METHODS: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCC) and 221 intrahepatic cholangiocarcinomas (ICCA). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver operating characteristic curves and cox regression modeling. RESULTS: Nestin was able to distinguish cHCC-CCA from HCC with AUC of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from ICCA (AUC of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA ("Nestin High", >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies. CONCLUSION: We show in different clinical settings that Nestin has a diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. LAY SUMMARY: Combined Hepatocellular-Cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) that lacks robust tissue biomarkers. We show in different clinical settings that Nestin immunohistochemical staining has a diagnostic value and is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy.