Profiling immunohistochemical expression of NOTCH1-3, JAGGED1, cMET, and phospho-MAPK in 100 carcinomas of unknown primary
Date
2012Author
Krikelis, D.
Goussia, Anna
Siozopoulou, V.
Bobos, M.
Petrakis, Dimitrios
Stoyianni, A.
Golfinopoulos, Vassilis
Cervantes, A.
Ciuleanu, T.
Fountzilas, George
Malamou-Mitsi, Vassiliki D.

Source
Clinical and Experimental MetastasisVolume
29Issue
6Pages
603-614Google Scholar check
Keyword(s):
Metadata
Show full item recordAbstract
Cancer of unknown primary (CUP) is a heterogeneous entity, managed on the basis of "one size fits all" therapeutic concepts; insights into the molecular biology of CUP are urgently needed. We retrospectively examined the immunohistochemical (IHC) expression of Notch1, 2, 3, Jagged1, cMET, and pMAPK biomolecules in 100 CUP tumors using tissue microarrays, aiming to study their correlation to clinicopathologic characteristics and prognostic utility for patient outcome. Notch3 and pMAPK were most frequently expressed (97 and 91 %, respectively). A linear correlation of Notch3 and cMET expression was found (p = 0.001), while pMAPK emerged as the major adverse prognostic factor (median overall survival OS 9 vs. 17 months, p = 0.016), carrying also a significantly positive predictive value (p = 0.02). Our study indicated a favorable prognostic impact of cMET expression in CUP, both in univariate (median OS 15 vs. 9 months, p = 0.05) and in multivariate analysis (Relative Risk RR for death 0.48, p = 0.025). cMET and Notch3 expression were found to be statistically more frequent in squamous carcinomas (positive in 90 % of cases), associated with a unique metastatic IHC pattern (cMET-high in soft tissue/lymph node metastases, p < 0.001, Notch3-high in visceral, peritoneal/pleural and soft tissue/lymph node metastases, p < 0.001). Our study points to the MAPK and cMET axes as crucial in defining cancer progression and outcome in CUP patients and, if validated, could justify attempts at their therapeutic modulation. © 2012 Springer Science+Business Media, LLC.
Collections
Cite as
Related items
Showing items related by title, author, creator and subject.
-
Article
Overexpression of the m4 and mα genes of the E(spl)-Complex antagonizes Notch mediated lateral inhibition
Apidianakis, Yiorgos; Nagel, A. C.; Chalkiadaki, Angeliki; Preiss, A.; Delidakis, Christos (1999)Intercellular signalling mediated by Notch proteins is crucial to many cell fate decisions in metazoans. Its profound effects on cell fate and proliferation require that a complex set of responses involving positive and ...
-
Article
The interplay between DSL proteins and ubiquitin ligases in Notch signaling
Pitsouli, Chrysoula; Delidakis, Christos (2005)Lateral inhibition is a pattern refining process that generates single neural precursors from a field of equipotent cells and is mediated via Notch signaling. Of the two Notch ligands Delta and Serrate, only the former was ...
-
Article
Role of conserved intracellular motifs in Serrate signalling, cis-inhibition and endocytosis
Glittenberg, M.; Pitsouli, Chrysoula; Garvey, C.; Delidakis, Christos; Bray, S. (2006)Notch is the receptor in a signalling pathway that operates in a diverse spectrum of developmental processes. Its ligands (e.g. Serrate) are transmembrane proteins whose signalling competence is regulated by the ...