Method for Improved Diagnosis of Dysplasias
The present invention relates to a method for improved diagnosis of dysplasias based on simultaneous detection of INK 4 a gene products and at least one marker for cell proliferation. Particularly the present invention provides a method for discriminating dysplastic cells over-expressing INK 4 a gene products from cells over-expressing INK 4 a gene products without being dysplastic by detection of a marker suitable for characterising the proliferation properties of the respective cell. The characterisation of the proliferation properties may comprise the detection of a marker or a set of markers characteristic for active cell proliferation and/or a marker or a set of markers characteristic for retarded or ceased cell proliferation. The method presented herein thus enables for a specific diagnosis of dysplasias in histological and cytological specimens.
1 .- 38 . (canceled)
39 . A kit comprising one or more probes for detecting the presence of one or more HPV nucleic acids from a high risk HPV subtype and antibody probes for specifically detecting at least one INK4a gene product and at least one cell proliferation marker gene product in biological samples, wherein the INK4a gene product is p16 INK4a and wherein the cell proliferation marker gene products are selected from the group consisting of Ki67 and PCNA.
40 . The kit of claim 39 comprising probes for the detection of p16 INK4a and Ki67.
41 . The kit of claim 39 comprising probes for the detection of p16 INK4a and PCNA.
42 . A kit comprising probes for detection of nucleic acids and gene products in biological samples, the probes consisting essentially of one or more probes for detecting the presence of one or more HPV nucleic acids from a high risk HPV subtype, antibody probes for specifically detecting p16 INK4a , and antibody probes for specifically detecting one or more cell proliferation marker gene products selected from the group consisting of Ki67 and PCNA.
43 . The kit of claim 42 wherein the antibody probes are one or more probes capable of specifically binding to p16 INK4a and one or more probes capable of specifically binding to Ki67.
44 . The kit of claim 42 wherein the antibody probes are one or more antibodies capable of specifically binding to p16 INK4a and one or more antibodies capable of specifically binding to PCNA.