Tumor tissue microarrays for rapid molecular profiling

Abstract

An array-based technology facilitates rapid correlated gene copy number and expression profiling of a very large number of human tumors. Hundreds of cylindrical tissue biopsies (diameter 0.6 mm) from morphologically representative regions of individual tumors can be arrayed in a single paraffin block. Consecutive sections from such arrays provide targets for parrallel in situ visualization and quantitation of DNA, RNA or protein targets. For example, amplifications of six loci (mybL2, erbB2, Cyclin-D1, myc, 17q23 and 20q13) were rapidly determined by fluorescence in situ hybridization from 372 ethanol-fixed breast cancers. Stratification of tumors by estrogen receptor and p53 expression data revealed distinct patterns of gene amplification in the various subgroups of breast cancer that may have prognostic utility. The tissue array technology is useful in the rapid molecular profiling of hundreds of normal and pathological tissue specimens or cultured cells.

1 . An automated system for making arrays of biological specimens for serial analysis, the system comprising: 
 a recipient array having a plurality of spaced elongated receptacles into which different biological specimens can be placed in fixed positions;    a reciprocating punch for introducing sequential biological specimens into different receptacles at assigned coordinate positions of the array; and    a recorder for identifying the biological specimen in each of the different receptacles at the assigned coordinate positions.    
   
   
       2 . The automated system of  claim 1 , further comprising a recorder for recording clinical or laboratory information about the biological specimen, or both.  
   
   
       3 . The automated system of  claim 2  further comprising a correlating device for correlating the clinical or laboratory information, or both, with the serial analysis performed on sequential sections of the recipient array.  
   
   
       4 . The system of  claim 1 , wherein the system further comprises a donor block providing a biological specimen.  
   
   
       5 . The system of  claim 4 , wherein the recipient array is formed by punching an elongated receptacle in the recipient array, automatically moving the recipient array or punch incrementally to align the punch with a new coordinate position on the recipient array, and punching another elongated receptacle in the new position.  
   
   
       6 . The system of  claim 5 , wherein the delivery mechanism delivers each biological specimen to a receptacle at a recorded position in the recipient array.  
   
   
       7 . The system of  claim 1 , further comprising an incremental positioner that incrementally moves the recipient array or delivery mechanism to the assigned coordinate positions after each sequential biological specimen is introduced into each receptacle.  
   
   
       8 . The system of  claim 1 , wherein the delivery mechanism is a punch which punches a tissue specimen from a donor receptacle.  
   
   
       9 . An automated system for making arrays of biological specimens, the system comprising: 
 a recipient punch configured to punch an array of receptacles in a recipient block;    a donor punch configured to introduce biological specimens into different receptacles in the recipient block at assigned coordinate positions of the array; and    a recorder for identifying the biological specimen in each of the difference receptacles at the assigned coordinate positions.    
   
   
       10 . The system of  claim 9 , further comprising a sectioning device for sectioning the recipient block into sections.