ArticleClinical & experimental metastasis2012
Profiling immunohistochemical expression of NOTCH1-3, JAGGED1, cMET, and phospho-MAPK in 100 carcinomas of unknown primary.
Article in Clinical & experimental metastasis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Synergic activity of FGFR2 and MEK inhibitors in the treatment of FGFR2-amplified cancers of unknown primary.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The association between NOTCH3 expression and the clinical outcome in the urothelial bladder cancer patients.Bosnian journal of basic medical sciences · 2022Article
- Cancer of unknown primary stem-like cells model multi-organ metastasis and unveil liability to MEK inhibition.Nature communications · 2021Article
- Progress in refining the clinical management of cancer of unknown primary in the molecular era.Nature reviews. Clinical oncology · 2020Review
- Exploring the biological hallmarks of cancer of unknown primary: where do we stand today?British journal of cancer · 2020Review
- A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma.Genome medicine · 2016Article
- Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin.BMC cancer · 2015Article
- Article
- Expression of Notch-1 and its clinical significance in different histological subtypes of human lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2013Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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