Disclosed herein is the discovery of a soluble MN / CA IX (s-CA IX) in body fluids, such as,
urine and serum. Said s-CA IX comprises the
extracellular domain of CA IX or portions thereof. The Predominant s-CA IX species is the
extracellular domain comprising a
proteoglycan-like (PG) domain and
carbonic anhydrase (CA) domain, and having a molecular weight of about 50 / 54 kilodaltons (kd) upon
Western blot. A smaller s-CA IX form of about 20 to about 30 kd comprising the CA domain or parts thereof, not linked to the PG domain, has also been found in body fluids. Diagnostic / prognostic methods for precancer and
cancer that detect or detect and quantitate said s-CA IX in body fluids, are described. Also disclosed herein is the coexpression of CA IX and HER-2 / neu / c-
erbB-2 that provides parallel, alternative and potentially synergistic diagnostic / prognostic and therapeutic strategies for precancer and
cancer. Further disclosed are new MN / CA IX-specific antibodies generated from MN / CA IX-deficient mice, preferably
monoclonal antibodies and immunoreactive fragments and engineered variants thereof. Such new MN / CA IX-specific antibodies, fragments and variants are useful diagnostically / prognostically and therapeutically for
cancer and precancer. Particularly preferred are the new
monoclonal antibodies, fragments and variants that are specific for the non-
immunodominant epitopes of MN / CA IX, which antibodies are, among other uses, useful to detect soluble MN / CA IX (s-CA IX) in body fluids, alone but preferably in combination with antibodies specific to the
immunodominant epitopes of MN / CA IX, for example, in a sandwich
assay.