WO2002018658A9 - Detection de la dysplasie epitheliale - Google Patents

Detection de la dysplasie epitheliale

Info

Publication number
WO2002018658A9
WO2002018658A9 PCT/US2001/041531 US0141531W WO0218658A9 WO 2002018658 A9 WO2002018658 A9 WO 2002018658A9 US 0141531 W US0141531 W US 0141531W WO 0218658 A9 WO0218658 A9 WO 0218658A9
Authority
WO
WIPO (PCT)
Prior art keywords
cells
epithelial
cell
population
analysis
Prior art date
Application number
PCT/US2001/041531
Other languages
English (en)
Other versions
WO2002018658A1 (fr
Inventor
Mark Rutenberg
Drore Eisen
Stephen Frist
Donald Alan Kristt
Original Assignee
Oralscan Lab Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Oralscan Lab Inc filed Critical Oralscan Lab Inc
Priority to AU2001294997A priority Critical patent/AU2001294997A1/en
Publication of WO2002018658A1 publication Critical patent/WO2002018658A1/fr
Publication of WO2002018658A9 publication Critical patent/WO2002018658A9/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Definitions

  • the present invention relates to a method for the detection of epithelial dysplasia using
  • FISH fluorescence in situ hybridization
  • SCC Squamous Cell Carcinomas
  • LHO heterozygosity
  • allelic gene loss has been detected not only in oral cancers, but in precancers as well.
  • CD44 variant 6 exhibits a change in its
  • MAbs monoclonal antibodies
  • MAb 17.13 are associated with epithelial dysplasia and may be of
  • GST glutathione S-transferase
  • the method involves proliferation markers such as the centromere-associated protein CENP-F,
  • CENP-F has been shown to be increased compared to specimens from normal oral
  • Detectable nuclear DNA content detectable may be
  • dysplasia which utilizes non-lacerational trans-epithelial biopsy specimens based on combining
  • Both '218 and '219 describe a system for selecting cells using computer assisted analysis.
  • dysplasia as well as further enhancing the system by conducting DNA ploidy analysis.
  • An object of the present invention is to provide a pathologist with the means to
  • Diagram 1 is a flowchart of a method in accordance with one embodiment of the
  • present invention which utilizes biomarker in the process of identifying cancerous
  • Diagram 2 is a flowchart of a method in accordance with another embodiment of the
  • Diagram 3 is a flowchart of a method in accordance with the preferred embodiment of
  • trans-epithelial sample is
  • sample may or may not be of significance since some lesions represent carcinoma, others
  • the present invention can be utilized as
  • the trans-epithelial sample of epithelial tissue is the trans-epithelial sample of epithelial tissue
  • sample may be analyzed with molecular diagnostic techniques
  • CD44 variant 6 protein by immunohistochemistry, monoclonal antibodies reactivity patterns,
  • cell cycle and proliferation markers such as the centromere-associated protein.
  • diagnostic techniques to cellular samples obtained with a noninvasive apparatus such as that cell cycle and proliferation markers such as the centromere-associated protein.
  • the molecular diagnostic techniques can be applied before or after the trans-epithelial
  • DNA ploidy determination may be
  • results of the computer analysis may be displayed as a DNA histogram.
  • a histogram is plotted based on the DNA ploidy of the cell population.
  • DNA ploidy of a cell population are eliminated due to the fact that the final DNA ploidy
  • Dysplasia is characterized as being either high-risk (aneuploid), intermediate-risk
  • a light indicator on the histogram alerts
  • the pathologist as to the DNA ploidy of the selected cell of interest.
  • Figs. 1-3 present data from superficial, intermediate and basal cell layers of the oral
  • Each quadrant contains a suspect cell found within the population under review and
  • Fig. 1 and 2 display atypical cells warranting further investigation of the respective
  • cytoplasmic ratio cytoplasmic ratio
  • nuclear crowding with a loss of polarity.
  • quadrants 10, 15, 20, 25, 30, 35, 40, 45, 50, and 55 show an increase in nuclear
  • quadrant 10 indicates that the cell of interest has a high nuclear to
  • cytoplasmic ratio (of 1: 9). This is observed by an increase in density as the nucleus absorbs a
  • FIG. 2 displays cells of a second patient also warranting further investigation
  • Quadrants 60 and 65 indicate a relatively high nuclear to cytoplasmic ratio of
  • quadrants 125 and 130 contain naked
  • Fig 3. shows cells positive for dysplasia or carcinoma. As indicated by the display in
  • the final interpretation of the image analysis histogram may be conducted in conjunction with the patient's history, biopsy findings, or any other pertinent test results.
  • all the image results may then be integrated into the corresponding biopsy report
  • a molecular diagnostic technique including but not limited to, fluorescence in situ hybridization, loss of heterozygosity, clonal genetic alterations, PCR, p53 expression and the expression pattern of CD44 variant 6 protein by immunohistochemistry, monoclonal antibodies reactivity patterns, glutathione
  • S-transferase activity measuring the number of nucleolar organizer regions and cell-cycle and proliferation markers such as the centromere-associated protein.
  • Analyzing the sample for a DNA ploidy analysis said DNA ploidy determination being conducted by a pathologist.
  • Analyzing the sample with a molecular diagnostic technique and/or for a DNA ploidy analysis said DNA ploidy determination being conducted by a pathologist and said molecular diagnostic technique including but not limited to, fluorescence in situ hybridization, loss of heterozygosity, clonal genetic alterations, PCR, p53 expression and the expression pattern of CD44 variant 6 protein by immunohistochemistry, monoclonal antibodies reactivity patterns, glutathione
  • S-transferase activity measuring the number of nucleolar organizer regions and cell-cycle and proliferation markers such as the centromere-associated protein.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne un système permettant de détecter la dysplasie épithéliale en examinant des cellules obtenues par un dispositif transépithélial ne provoquant pas de déchirure. Ce système sélecte des cellules suspectes en fonction d'une morphologie ou d'une cytométrie anormale et/ou à l'aide de techniques de diagnostic moléculaire. Selon un mode de réalisation préféré, les résultats de l'analyse informatique sont affichés sous forme d'un histogramme et les images des cellules suspectes sont étudiées par un pathologiste cellule par cellule pour rechercher l'ADN-ploïdie.
PCT/US2001/041531 2000-08-14 2001-08-03 Detection de la dysplasie epitheliale WO2002018658A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001294997A AU2001294997A1 (en) 2000-08-14 2001-08-03 Detection of epithelial dysplasia

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US22518600P 2000-08-14 2000-08-14
US60/225,186 2000-08-14

Publications (2)

Publication Number Publication Date
WO2002018658A1 WO2002018658A1 (fr) 2002-03-07
WO2002018658A9 true WO2002018658A9 (fr) 2003-05-15

Family

ID=22843883

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/041531 WO2002018658A1 (fr) 2000-08-14 2001-08-03 Detection de la dysplasie epitheliale

Country Status (2)

Country Link
AU (1) AU2001294997A1 (fr)
WO (1) WO2002018658A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2487248A1 (fr) * 2006-05-10 2012-08-15 The Board of Regents of the University of Texas System Détection de biomarqueurs tumoraux dans le cancer de la bouche

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000004833A1 (fr) * 1998-07-23 2000-02-03 The Oralscan/Trylon Joint Venture Instrument permettant de prelever des echantillons trans-epitheliaux sur une surface corporelle sans lacerer celle-ci et methode afferente
NZ513118A (en) * 1999-01-25 2004-02-27 Newton Lab Inc Imaging of a tissue by detecting polarized and unpolarized images to form a processed image of a region of interest

Also Published As

Publication number Publication date
WO2002018658A1 (fr) 2002-03-07
AU2001294997A1 (en) 2002-03-13

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