In the phrase you mention there are two "de". When you say "La casa de Manuel", "De" is used to express possession. Manuel possesses that house. On the other hand, when you say "De dos pisos", you're using the preposition to describe a noun using another noun. "La casa de dos pisos", "El vaso de agua", "El juego de fútbol". In all of them "de" is used to describe nouns.