Prognostic significance of WNT and hedgehog pathway activation markers in cancer of unknown primary
Malamou-Mitsi, Vassiliki D.
SourceEuropean journal of clinical investigation
Google Scholar check
MetadataShow full item record
Background: Cancer of unknown primary (CUP) possesses distinct biology and peculiar natural history, in which the roles of the winged and hedgehog signalling pathways are unclear. Materials and methods: We constructed tissue microarrays and studied the immunohistochemical (IHC) expression of β-catenin, smoothened (SMO) and the transcription factors TCF, LEF, GLI1 in 87 CUP cases for prognostic significance. Results: A low rate of IHC expression of proteins was seen, the cut-off used being any expression in ≥ 1% of tumour cells. At univariate analysis, only nuclear IHC SMO expression displayed a statistically significant association with favourable outcome [median Overall survival (OS) of 19 months in SMO-positive vs. 12 months in SMO-negative cases, P = 0·01]. An activated Wnt pathway, defined as IHC expression of any of nuclear β-catenin, TCF and LEF, was significantly associated with favourable progression free survival (median 9 vs. 5 months, P = 0·037) and OS (median 19 vs. 13 months, P = 0·04). This prognostic impact on OS was mainly driven by nuclear expression of TCF and/or LEF (P = 0·03). No prognostic significance of the hedgehog pathway activation status, defined as IHC expression of SMO or nuclear GLI1, could be established. A favourable prognostic impact of the concurrent activation of both pathways was observed. A trend for association of activated Wnt with response to chemotherapy (responders 67% among activated Wnt cases vs. 35% among nonactivated Wnt cases, P = 0·07) was observed in CUP adenocarcinomas. Conclusions: Activation of the Wnt pathway was a positive prognostic factor in a small CUP series, possibly via enhanced chemosensitivity. Independent validation is warranted. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.
Showing items related by title, author, creator and subject.
Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: Interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes Pentheroudakis, George; Kotoula, V.; Roock, W. De; Kouvatseas, G.; Papakostas, P.; Makatsoris, T.; Papamichael, D.; Xanthakis, I.; Sgouros, J.; Televantou, D.; Kafiri, G.; Tsamandas, A. C.; Razi, E. D.; Galani, E.; Bafaloukos, Dimitrios; Efstratiou, I.; Bompolaki, I.; Pectasides, Dimitrios; Pavlidis, Nicholas; Tejpar, S.; Fountzilas, George (2013)Background: More than half of patients with KRAS-wild type advanced colorectal cancer (CRC) fail anti-EGFR monoclonal antibodies. We studied EGFR-axis messenger RNA (mRNA) expression and RAS, RAF, PIK3CA mutations in order ...
Kamposioras, K.; Pentheroudakis, George; Pavlidis, Nicholas (2013)Background: Cancer of unknown primary (CUP) ranks among the ten most common malignancies worldwide. Cancer of unknown primary presents as disseminated disease, has a dismal prognosis and remains a diagnosis of exclusion. ...
Serous papillary peritoneal carcinoma: Unknown primary tumour, ovarian cancer counterpart or a distinct entity? A systematic review Pentheroudakis, George; Pavlidis, Nicholas (2010)Introduction: Serous peritoneal papillary carcinoma (SPPC), though managed according to ovarian cancer therapeutic principles, has been variably considered as an ovarian cancer counterpart, a peritoneal malignancy with ...