Cell-based detection and differentiation of lung cancer

Abstract

The present invention provides a method for detecting and differentiating disease states with high sensitivity and specificity. The method allows for a determination of whether a cell-based sample contains abnormal cells and, for certain diseases, is capable of determining the histologic type of disease present. The method detects changes in the level and pattern of expression of the molecular markers in the cell-based sample. Panel selection and validation procedures are also provided.

1 .- 34 . (canceled)  
     
     
         35 . A panel for discriminating adenocarcinoma among other types of lung cancer, wherein the panel comprises a plurality of probes each of which specifically binds to a marker associated with a specific type of lung cancer, wherein: 
 (a) the pattern of binding of the component probes of the panel to cells in a cytology sample discriminates adenocarcinoma among other types of lung cancer, and    (b) the plurality of probes comprises a probe that binds to Mucin 1 or a correlate marker thereof and a probe that binds to thyroid transcription factor 1 or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         36 . The panel of  claim 35 , wherein the plurality of probes further comprises at least one probe that binds to a marker selected from the group consisting of VEGF, SP-A, BCL-2, ER-related (p29), Glut 3, and correlate markers thereof as depicted in the correlation matrix shown in  FIG. 4 .  
     
     
         37 . A panel for discriminating squamous cell carcinoma among other types of lung cancer, wherein the panel comprises a plurality of probes each of which specifically binds to a marker associated with a specific type of lung cancer, wherein: 
 (a) the pattern of binding of the component probes of the panel to cells in a cytology sample discriminates squamous cell carcinoma among other types of lung cancer, and    (b) the plurality of probes comprises a probe that binds to CD44v6 or a correlate marker thereof and a probe that binds to ER-related (p29) or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         38 . The panel of  claim 37 , wherein the plurality of probes further comprises at least one probe that binds to a marker selected from the group consisting of VEGF, thrombomodulin, Glut 1, MAGE 3, and correlate markers thereof as depicted in the correlation matrix shown in  FIG. 4 .  
     
     
         39 . A panel for discriminating large cell carcinoma among other types of lung cancer, wherein the panel comprises a plurality of probes each of which specifically binds to a marker associated with a specific type of lung cancer, wherein: 
 (a) the pattern of binding of the component probes of the panel to cells in a cytology sample discriminates large cell carcinoma among other types of lung cancer, and    (b) the plurality of probes comprises a probe that binds to VEGF or a correlate marker thereof and a probe that binds to P120 or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         40 . The panel of  claim 39 , wherein the plurality of probes further comprises a probe that binds to Cyclin A or a correlate marker thereof as depicted in the correlation matrix shown in  FIG. 4 .  
     
     
         41 . A panel for discriminating mesothelioma among other types of lung cancer, wherein the panel comprises a plurality of probes each of which specifically binds to a marker associated with a specific type of lung cancer, wherein: 
 (a) the pattern of binding of the component probes of the panel to cells in a cytology sample discriminates mesothelioma among other types of lung cancer, and    (b) the plurality of probes comprises a probe that binds to CD44v6 or a correlate marker thereof, a probe that binds to PCNA or a correlate marker thereof and a probe that binds to HERA or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         42 . A panel for discriminating mesothelioma among other types of lung cancer, wherein the panel comprises a plurality of probes each of which specifically binds to a marker associated with a specific type of lung cancer, wherein: 
 (a) the pattern of binding of the component probes of the panel to cells in a cytology sample discriminates mesothelioma among other types of lung cancer, and    (b) the plurality of probes comprises a probe that binds to CD44v6 or a correlate marker thereof as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         43 . A panel for discriminating mesothelioma among other types of lung cancer, wherein the panel comprises a plurality of probes each of which specifically binds to a marker associated with a specific type of lung cancer, wherein: 
 (a) the pattern of binding of the component probes of the panel to cells in a cytology sample discriminates mesothelioma among other types of lung cancer, and    (b) the plurality of probes comprises a probe that binds to PCNA or a correlate marker thereof as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         44 . A panel for discriminating small cell carcinoma among other types of lung cancer, wherein the panel comprises a plurality of probes each of which specifically binds to a marker associated with a specific type of lung cancer, wherein: 
 (a) the pattern of binding of the component probes of the panel to cells in a cytology sample discriminates small cell carcinoma among other types of lung cancer, and    (b) the plurality of probes comprises a probe that binds to PCNA or a correlate marker thereof, a probe that binds to BCL-2 or a correlate marker thereof, and a probe that binds to EGFR or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         45 . A cell-based method for discriminating adenocarcinoma among other types of lung cancer comprising: 
 (a) contacting cells from a cytology sample on one or more microscope slides with a panel comprising a plurality of probes; and    (b) analyzing the pattern of binding of the component probes of the panel to cells in the cytology sample to discriminate adenocarcinoma among other types of lung cancer,    wherein the plurality of probes comprises a probe that binds to Mucin 1 or a correlate marker thereof and a probe that binds to thyroid transcription factor 1 or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         46 . The method of  claim 45 , wherein the plurality of probes further comprises at least one probe that binds to a marker selected from the group consisting of VEGF, SP-A, BCL-2, ER-related (p29), Glut 3, and correlate markers thereof as depicted in the correlation matrix shown in  FIG. 4 .  
     
     
         47 . A cell-based method for discriminating squamous cell carcinoma among other types of lung cancer comprising: 
 (a) contacting cells from a cytology sample on one or more microscope slides with a panel comprising a plurality of probes; and    (b) analyzing the pattern of binding of the component probes of the panel to cells in the cytology sample to discriminate squamous cell carcinoma among other types of lung cancer,    wherein the plurality of probes comprises a probe that binds to CD44v6 or a correlate marker thereof and a probe that binds to ER-related (p29) or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         48 . The method of  claim 47 , wherein said plurality of probes further comprises at least one probe that binds to a marker selected from the group consisting of VEGF, thrombomodulin, Glut 1, MAGE 3, and correlate markers thereof as depicted in the correlation matrix shown in  FIG. 4 .  
     
     
         49 . A cell-based method for discriminating large cell carcinoma among other types of lung cancer comprising: 
 (a) contacting cells from a cytology sample on one or more microscope slides with a panel comprising a plurality of probes; and    (b) analyzing the pattern of binding of the component probes of the panel to cells in the cytology sample to discriminate large cell carcinoma among other types of lung cancer,    wherein the plurality of probes comprises a probe that binds to VEGF or a correlate marker thereof and a probe that binds to P120 or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         50 . The method of  claim 49 , wherein the plurality of probes further comprises a probe that binds to Cyclin A or a correlate marker thereof as depicted in the correlation matrix shown in  FIG. 4 .  
     
     
         51 . A cell-based method for discriminating mesothelioma among other types of lung cancer comprising: 
 (a) contacting cells from a cytology sample on one or more microscope slides with a panel comprising a plurality of probes; and    (b) analyzing the pattern of binding of the component probes of the panel to cells in the cytology sample to discriminate mesothelioma among other types of lung cancer,    wherein the plurality of probes comprises a probe that binds to CD44v6 or a correlate marker thereof, a probe that binds to PCNA or a correlate marker thereof, and a probe that binds to HERA or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         52 . A cell-based method for discriminating mesothelioma among other types of lung cancer comprising: 
 (a) contacting cells from a cytology sample on one or more microscope slides with a panel comprising a plurality of probes; and    (b) analyzing the pattern of binding of the component probes of the panel to cells in the cytology sample to discriminate mesothelioma among other types of lung cancer,    wherein the plurality of probes comprises a probe that binds to CD44v6 or a correlate marker thereof as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         53 . A cell-based method for discriminating mesothelioma among other types of lung cancer comprising: 
 (a) contacting cell's from a cytology sample on one or more microscope slides with a panel comprising a plurality of probes; and    (b) analyzing the pattern of binding of the component probes of the panel to cells in the cytology sample to discriminate mesothelioma among other types of lung cancer,    wherein the plurality of probes comprises a probe that binds to PCNA or a correlate marker thereof as depicted in the correlation matrix shown in  FIG. 4 .    
     
     
         54 . A cell-based method for discriminating small cell carcinoma among other types of lung cancer comprising: 
 (a) contacting cells from a cytology sample on one or more microscope slides with a panel comprising a plurality of probes; and    (b) analyzing the pattern of binding of the component probes of the panel to cells in the cytology sample to discriminate small cell carcinoma among other types of lung cancer,    wherein the plurality of probes comprises a probe that binds to PCNA or a correlate marker thereof, a probe that binds to BCL-2 or a correlate marker thereof, and a probe that binds to EGFR or a correlate marker thereof, wherein “correlate markers” are as depicted in the correlation matrix shown in  FIG. 4 .