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WO2002018658A1 - Detection de la dysplasie epitheliale - Google Patents

Detection de la dysplasie epitheliale Download PDF

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Publication number
WO2002018658A1
WO2002018658A1 PCT/US2001/041531 US0141531W WO0218658A1 WO 2002018658 A1 WO2002018658 A1 WO 2002018658A1 US 0141531 W US0141531 W US 0141531W WO 0218658 A1 WO0218658 A1 WO 0218658A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
epithelial
sample
cell
abnormalities
Prior art date
Application number
PCT/US2001/041531
Other languages
English (en)
Other versions
WO2002018658A9 (fr
Inventor
Mark Rutenberg
Drore Eisen
Stephen Frist
Donald Alan Kristt
Original Assignee
Oralscan Laboratories, 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 Laboratories, Inc. filed Critical Oralscan Laboratories, 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

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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
  • oral lesions transform, de novo, into carcinoma without passing through a dysplastic, pre-
  • FISH fluorescence in situ hybridization
  • cyclin Dl also has been demonstrated in cancers of the head and neck.
  • SCC Squamous Cell Carcinomas
  • LHO heterozygosity
  • allelic gene loss has been detected not only
  • p53 is an early event in oral carcinogenesis
  • CD44v6 exhibits a change in its expression pattern progressively from non-neoplastic
  • epithelial lesions expressed positive staining patterns comparable to those of the normal
  • Another marker for early oral cancer are the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by the antigens recognized by
  • Altered reactivity patterns of MAb 17.13 are associated with epithelial dysplasia and may be of assistance in detecting precancerous
  • GST glutathione S-transferase
  • centromere-associated protein CENP-F which is a centromere-associated protein
  • CENP-F has been shown to be increased compared to specimens from normal oral
  • dysplasia which utilizes non-lacerational trans-epithelial biopsy specimens based on
  • 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 and precancerous cells.
  • Diagram 2 is a flowchart of a method in accordance with another embodiment of
  • Diagram 3 is a flowchart of a method in accordance with the preferred embodiment
  • epithelial sample is preferably obtained using the device disclosed in the '186 application,
  • sample may or may not be of significance since some lesions represent carcinoma, others
  • the present invention can be utilized
  • tissue is examined for abnormalities in cellular morphology, DNA concentration, and
  • Atypical cells are selected for by the computer and a DNA ploidy
  • sample may be analyzed with molecular diagnostic techniques
  • An advantage of this invention is the application of a DNA ploidy analysis
  • Another advantage of this invention is the increased sensitivity compared to all existing methods by themselves, including histopathology, cytology, and
  • the molecular diagnostic techniques can be applied before or after the trans-
  • epithelial sample of epithelial tissue is examined for abnormalities in cellular morphology
  • DNA ploidy determination may be made either independently or in conjunction with the
  • the 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.
  • final DNA ploidy determination is conducted by a pathologist on a cell by cell basis.
  • Dysplasia is characterized as being either high-risk (aneuploid), intermediate-risk
  • an indicator on the histogram serves to represent the relative DNA ploidy determination
  • 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
  • Fig. 1 and 2 display atypical cells warranting further investigation of the respective
  • quadrant 10 indicates that the cell of interest has a
  • nucleus absorbs a larger portion of the cytometric dye.
  • cells of interest gives the pathologist a greater degree of accuracy. Further investigation may include additional harvesting of cells from the region of interest.
  • Fig. 2 displays cells of a second patient also warranting further
  • Quadrants 60 and 65 indicate a relatively high nuclear to
  • the pathologist is able to determine that the low nuclear to cytoplasmic ratio is attributed to a cell which is no longer intact.
  • Fig 3. shows cells positive for dysplasia or carcinoma. As indicated by the display in the bottom left hand corner of quadrants 150, 155 and 160, there is a dramatic increase in
  • the final interpretation of the image analysis histogram may be conducted in
  • all the image results may then be integrated into the corresponding biopsy

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 true WO2002018658A1 (fr) 2002-03-07
WO2002018658A9 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)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007134189A3 (fr) * 2006-05-10 2008-07-03 Univ Texas Détection de biomarqueurs tumoraux dans le cancer de la bouche

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000043750A2 (fr) * 1999-01-25 2000-07-27 Newton Laboratories, Inc. Imagerie de tissus au moyen de lumiere polarisee
US6258044B1 (en) * 1998-07-23 2001-07-10 Oralscan/Trylon Joint Venture Apparatus and method for obtaining transepithelial specimen of a body surface using a non-lacerating technique

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6258044B1 (en) * 1998-07-23 2001-07-10 Oralscan/Trylon Joint Venture Apparatus and method for obtaining transepithelial specimen of a body surface using a non-lacerating technique
WO2000043750A2 (fr) * 1999-01-25 2000-07-27 Newton Laboratories, Inc. Imagerie de tissus au moyen de lumiere polarisee

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BAHAR R. ET AL.: "CD44 variant 6 (CD44vl) expression as a progression marker in benign, premalignant and malignant oral epithelial tissues", INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, vol. 26, no. 6, December 1997 (1997-12-01), pages 443 - 446, XP002907037 *
ITAKURA Y. ET AL.: "DNA ploidy, P53 expression and cellular proliferation in normal epithelium and squamous dysplasia of non-cancerous and cancerous human oesophagi", ANTICANCER RESEARCH, vol. 16, no. 1, January 1996 (1996-01-01) - February 1996 (1996-02-01), pages 201 - 208, XP002907038 *
YOKOZAKI M. ET AL.: "Differentiation of atypical adenomatous hyperplasia and adenocarcinoma of the lung by use of DNA ploidy and morphometric analysis", MODERN PATHOLOGY, vol. 9, no. 12, December 1996 (1996-12-01), pages 1156 - 1164, XP002907036 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007134189A3 (fr) * 2006-05-10 2008-07-03 Univ Texas Détection de biomarqueurs tumoraux dans le cancer de la bouche
EP2021491A4 (fr) * 2006-05-10 2010-02-24 Univ Texas Détection de biomarqueurs tumoraux dans le cancer de la bouche

Also Published As

Publication number Publication date
AU2001294997A1 (en) 2002-03-13
WO2002018658A9 (fr) 2003-05-15

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