Cell analysis method, cell analyzer and sample screening method

Abstract

Disclosed is a cell analysis method comprising: extracting target cells from a population of cells derived from an epithelial tissue on the basis of N/C ratio representing a relative size of a nucleus to a cytoplasm; classifying the target cells into at least a first group and a second group by difference of amount of DNA; and evaluating a pathology of the epithelial tissue by comparing a ratio of numbers of cells between the first and second groups with a threshold; wherein the threshold varies according to a proportion of the target cells in the population.

What is claimed is: 
     
         1 . A cell analysis method comprising:
 extracting target cells from a population of cells derived from an epithelial tissue on the basis of N/C ratio representing a relative size of a nucleus to a cytoplasm;   classifying the target cells into at least a first group and a second group by difference of amount of DNA; and   evaluating a pathology of the epithelial tissue by comparing a ratio of numbers of cells between the first and second groups with a threshold;   wherein the threshold varies according to a proportion of the target cells in the population.   
     
     
         2 . The cell analysis method of  claim 1 , further comprising:
 measuring a measurement specimen including cells collected from epithelial tissue to obtain a first parameter of a nucleus size, a second parameter of a cell size, and a third parameter of an amount of DNA for at least respective some of the cells; and   obtaining the N/C ratio on the basis of the first and second parameters.   
     
     
         3 . The cell analysis method of  claim 1 , wherein
 the target cells are epithelial cells having a greater N/C ratio than a predetermined value.   
     
     
         4 . The cell analysis method of  claim 1 , wherein
 the threshold varies according to a ratio of a number of the target cells to a number of other cells having smaller N/C ratio than that of the target cells.   
     
     
         5 . The cell analysis method of  claim 1 , wherein
 the target cells are classified into at least the first group having an amount of DNA corresponds to cell cycle G0 to G1 phases and a second group having an amount of DNA greater than that of cells in the G0 to G1 phases.   
     
     
         6 . The cell analysis method of  claim 5 , comprising
 prompting retest of the epithelial tissue or a subject when a ratio of a numbers of cells in the second group relative to a number of cells in the first group is greater than or equal to the threshold.   
     
     
         7 . The cell analysis method of  claim 1 , comprising:
 avoiding the evaluation of pathology if the number of the target cells is not sufficient to the evaluation.   
     
     
         8 . The cell analysis method of  claim 1 , comprising:
 outputting an evaluation result together with information representing quantitatively or qualitatively the proportion of the target cells.   
     
     
         9 . The cell analysis method of  claim 1 , further comprising
 introducing a measurement specimen containing cells derived from an epithelial tissue collected from a subject into a flow cell;   irradiating the cells in the measurement specimen running in the flow cell and thereby producing light scatter and fluorescence;   detecting scattered light to output first signal waveform according to an intensity of the scattered light; and   detecting fluorescence to output second signal waveform according to an intensity of the fluorescence.   
     
     
         10 . The cell analysis method of  claim 9 , wherein
 a width of a wave of the first signal waveform corresponds to a size of a cell; and   a width of a wave of the second signal waveform corresponds to a size of a nucleus.   
     
     
         11 . The cell analysis method of  claim 10 , wherein
 an area under a wave of the second signal waveform corresponds to an amount of DNA.   
     
     
         12 . The cell analysis method of  claim 1 , wherein
 the epithelial tissue is epithelial tissue of uterine cervix.   
     
     
         13 . The cell analysis method of  claim 1 , wherein
 the target cells are cells on a basal layer side among the epithelial cells.   
     
     
         14 . A cell analyzer comprising:
 a measurement apparatus comprising a cytometer; and   a data processing device connected to the cytometer, and comprising a processor programmed to process data of cells obtained from the cytometer by:
 extracting target cells from a population of cells derived from an epithelial tissue on the basis of N/C ratio representing a relative size of a nucleus to a cytoplasm; 
 determining a threshold according to a proportion of the target cells in the population; 
 classifying the target cells into at least a first group and a second group by difference of amount of DNA; and 
 evaluating a pathology of the epithelial tissue by comparing a ratio of numbers of cells between the first and second groups with the threshold determined. 
   
     
     
         15 . The cell analyzer of  claim 14 , wherein
 the data processing device is programmed to perform operations comprising:
 obtaining, for each cell, first data regarding a cell nucleus size, second data regarding a cell size, and third data regarding an amount of DNA of the cell, based on a detection result by the cytometer; 
 calculating the N/C ratio based on the first and second data; and 
 calculating the amount of DNA based on the third data. 
   
     
     
         16 . The cell analyzer of  claim 14 , further comprising:
 an output unit, wherein   the data processing device is further programmed to cause the output unit to output an evaluation result together with information representing quantitatively or qualitatively the proportion of the target cells.   
     
     
         17 . The cell analyzer of  claim 14 , wherein
 the cytometer comprises:
 a flow cell through which a measurement specimen containing the cells prepared from the epithelial tissue runs; 
 a light source that irradiates the measurement specimen running in the flow cell; 
 a first detector that detects light scattered by the irradiation to output first signal waveform according to an intensity of the scattered light; and 
 a second detector that detects fluorescence produced by the irradiation to output second signal waveform according to an intensity of the fluorescence. 
   
     
     
         18 . The cell analyzer of  claim 17 , wherein
 the data processing device is programmed to:
 extract a parameter of a size of a cell from a width of a wave of the first signal waveform; and 
 extract a parameter of a size of a nucleus from a width of a wave of the second signal waveform. 
   
     
     
         19 . The cell analyzer of  claim 17 , wherein
 the data processing device is programmed to extract a parameter of an amount of DNA from an area under a wave of the second signal waveform.   
     
     
         20 . A sample screening method comprising:
 quantifying target cells in a measurement specimen prepared from a sample of epithelial tissue on the basis of N/C ratio representing a relative size of a nucleus to a cytoplasm;   evaluating on the basis of quantity of the target cells whether the sample was appropriately collected from a subject;   screening on the basis of amounts of DNA of the target cells the sample into groups of a cancer-suspected sample and other if the sample was appropriately collected;   avoiding the screening if the collection of sample was inappropriate.