Strong nuclear EGFR expression in colorectal carcinomas is associated with cyclin-D1 but not with gene EGFR amplification

Abstract

BackgroundPrognostic and predictive significance of epidermal growth factor receptor (EGFR) in colorectal carcinomas (CRCs) is still controversial. The aim of the present study was to explore and correlate membrane and nuclear EGFR and cyclin-D1 protein expression with EGFR gene status of tumor cells.MethodsImmunohistochemical and FISH analysis was performed on 135 archival formalin fixed and paraffin embedded CRCs.ResultsStrong membrane and strong nuclear EGFR staining was detected in 16% and 57% of cases, respectively, and strong cyclin-D1 expression in 57% samples. Gene EGFR amplification was identified in 5.9% and polysomy in 7.4% of cases, while 87% showed no EGFR gene changes. A statistically significant difference was only found between tumor grade and expression of membrane EGFR, while nuclear EGFR and cyclin-D1 expression was not associated with the clinicopathologic characteristics analyzed. Tumor cells displaying gene amplification and strong protein membrane EGFR expression overlapped, while EGFR gene status showed no correlation with nuclear EGFR and cyclin-D1. There was no association between membrane EGFR and cyclin-D1, whereas nuclear EGFR expression was strongly related to cyclin-D1 expression.ConclusionsStudy results revealed heterogeneity among CRCs, which could have a predictive value by identifying biologically and probably clinically different subsets of tumors with the possibly diverse response to anti-EGFR therapies.

Right-sided rhabdoid colorectal tumors might be related to the Serrated Pathway

“…Usually, RCTs express high levels of EGFR [1,2], a finding that is recurrent also in other subgroups of highly aggressive CRCs . These results suggest that a combined assessment of CDX2, Vimentin and EGFR may be of clinical value to make a differential diagnosis, to predict a poor patients’ outcome or to choose the best fit biological therapy [17,18]. INI1 loss-of-function mutations have been identified in pediatric MRTs, whereas their role in adult extra-renal rhabdoid tumors is still elusive [5,6].…”

Prognostic significance and targeting of HER family in colorectal cancer

“…to therapy, tumour aggressiveness and poor survival (37)(38)(39)(40)(41)(42)(43). This demonstrates the complex mechanisms by which HER signalling may be activated and the need for further studies to unravel the role of nuclear HER family members in the proliferation and progression of tumour cells as wells as its potential as a prognostic marker, predictive biomarker and therapeutic target in colorectal cancer patients (39,40,(44)(45)(46)(47). Abbreviations: IHC Immunohistochemistry, FISH fluorescence in situ hybridisation, CISH chromogenic in situ hybridisation, RT-PCR real-time polymerase chain reaction, AR amphiregulin, EPI epiregulin, met metastatic…”

“…wild-type, mutated, soluble, phosphorylated EGFR) and their cellular locations (e.g. cytoplasmic, membranous or nuclear) and such studies should be conducted on a larger group of patients using a standard scoring system (39,40,44,56,(68)(69)(70)(71).…”

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“…Na mijelomskim stanicama analizirana je ekspresija ciklina D1, a sve u cilju predikcije odgovora na terapiju s bortezomibom. Pretpostavka je bila da će ekspresija biti udružena s boljom prognozom kao što su to dosadašnja istraživanja pokazala za karcinom dojke gdje je ekspresija ciklina D1 u premenopauzalnih pacijentica korelirala s dužim preživljenjem 2 , ili u kolorektalnom karcinomu gdje je udružena ekspresija nuklearnog EGFR-a i ciklina D1 imala kliničku implikaciju 3 . U sklopu mikrookoliša multiplog mijeloma istraživana je angiogeneza.…”