Britain's absence from the EU's 60th birthday celebrations is "a sad moment", EU chief Jean-Claude Juncker has said.
The president of the European Commission also restated his view that the UK's departure from the bloc after more than 40 years was "a tragedy".
Mr Juncker was speaking at a meeting of the remaining 27 member states in Rome to mark the 60th anniversary of the signing of the Treaty of Rome, the founding agreement of the EU.
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Britain is set to trigger Article 50 next Wednesday that will start the formal two-year divorce proceedings from Brussels.
As he arrived at the anniversary ceremony, Mr Juncker said: "It is a very sad moment, I do think that the Brexit, the exit of Britain, is a tragedy."
But he believed the EU was strong enough to see through the challenges it faced from economic problems and the migration crisis to the terrorist threat and rise of populist anti-Europe movements.
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Recalling how the new Europe was built from the ashes of World War II, he said: "Daunting as they are, the challenges we face today are in no way comparable to those faced by the founding fathers."
EU Council President Donald Tusk also called on government heads to be strong.
He said: "Prove today that you are the leaders of Europe, that you can care for this great legacy we inherited from the heroes of European integration 60 years ago.
"Europe as a political entity will either be united, or will not be at all. Only a united Europe can be a sovereign Europe in relation to the rest of the world.
"Only a sovereign Europe guarantees independence for its nations, guarantees freedom for its citizens."
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Pope Francis had earlier warned on the eve of the summit that the crisis-hit bloc "risks dying" without a new vision.
Meanwhile, Washington has congratulated the EU on its 60th birthday, in a shift in tone for President Donald Trump's administration which has been sceptical towards Brussels.
A White House statement said: "Our two continents share the same values and, above all, the same commitment to promote peace and prosperity through freedom, democracy, and the rule of law."
Security was tight at the Rome meeting with snipers on rooftops, drones in the skies and 3,000 police officers on the streets following the terror attack in London on Wednesday.