HISTOMETRIC ANALYSIS OF PREMALIGNANT ENDOMETRIAL LESIONS

Summary

Principal Investigator: FRANCISCO AR GARCIA
Abstract: Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States. It accounts for about 36,000 cases of invasive cancer each year and is among the top five neoplasms affecting women. Hyperplastic abnormalities of the endometrium follow a continuum of severity, with the risk of progression to carcinoma being related to the complexity of the lesion. At this time dilation and curettage with hysteroscopy, remain the major means of diagnosis. The current management of atypical endometrial hyperplasia is limited to hysterectomy. The overall goal of this research is to establish the foundation for the objective characterization of hyperplastic endometrial lining abnormalities associated with neoplasia of the uterine corpus, based on computer histometric/karyometric analysis. We hypothesize that: 1) The orderly progression from normality, to simple hyperplasia, atypical hyperplasia, and endometrial carcinoma in the uterine lining has distinct morphometric characteristics that can be identified using computer-based histometric analysis. 2) Endometrial adenocarcinoma causes distinct identifiable changes in adjacent hyperplastic and otherwise normal endometrial surfaces, which permit its identification prior to hysterectomy. 3) The responsiveness of atypical hyperplasia to a chemopreventive regimen can be objectively quantified using histometric/karyometric analysis. Our specific aims are to: 1) Develop procedures for the automated digital processing of high resolution microscopic images of histopathologic sections of endometrial biopsies and hysterectomy specimens, including the development of a knowledge file for automated scene segmentation and karyometry. 2) Establish an objective, numeric assessment and grading system for endometrial lesions. 3) Define a nuclear signature of preneoplastic endometrial lesions. These will be accomplished within the context of an ongoing two-part study of atypical hyperplasia (GOG Protocol 167). The ubiquity of preneoplastic abnormalities of the endometrial lining of the uterus, and the potential morbidity, time loss and expense associated with their surgical therapy, require the development of novel diagnostic modalities that reliably predict malignant potential. Digital microscopy and nuclear morphometric analysis will extend the utility of the histopathologic analysis of otherwise negative endometrial biopsy material, by allowing the identification of women with synchronous endometrial carcinoma, or at risk for malignant progression of their hyperplasia. This will allow the development and testing of chemopreventive interventions in low risk patients, and facilitate efficient surgical therapy in those women with potentially aggressive disease. Such capabilities could prevent unnecessary surgery, as well as the vast majority of advanced endometrial cancers. The technique of computerized morphometric analysis has tremendous potential to increase our understanding of the biological behavior of endometrial cancer, as well as revolutionize its diagnosis and treatment endometrial cancer. This proposed research project fits within the context, of a highly structured, multi-faceted, Mentored Patient Oriented Research Career Development Plan that focuses on the prevention and control of preneoplastic gynecologic disease. It utilizes the unique resources available at the University of Arizona, to foster an environment in which academic productivity is optimized and the necessary supervision is received to insure a successful career in clinical investigation.
Funding Period: 1999-09-01 - 2006-02-28
more information: NIH RePORT

Top Publications

  1. pmc Green tea compound in chemoprevention of cervical cancer
    Changping Zou
    Guangxi Medical University, Nanning City, China
    Int J Gynecol Cancer 20:617-24. 2010
  2. pmc Karyometry in atypical endometrial hyperplasia: a Gynecologic Oncology Group study
    Peter H Bartels
    University of Arizona Cancer Center, Tucson, AZ, USA
    Gynecol Oncol 125:129-35. 2012
  3. ncbi Karyometry in the early detection and chemoprevention of intraepithelial lesions
    J Ranger-Moore
    University of Arizona, P O Box 245024, Tucson, Arizona, AZ 85724 5024, USA
    Eur J Cancer 41:1875-88. 2005

Scientific Experts

  • James Ranger Moore
  • Peter H Bartels
  • Changping Zou
  • J Ranger-Moore
  • Michael Yozwiak
  • John Curtin
  • Lisa M Hess
  • Cornelia L Trimble
  • Hubert G Bartels
  • Peter C Lim
  • Steven Silverberg
  • James Kauderer
  • David S Alberts
  • Francisco A R Garcia
  • Richard J Zaino
  • Zhengping Hao
  • H H Sherry Chow
  • Huaguang Liu
  • Francisco Garcia
  • Jean M Feugang
  • G M Mariuzzi
  • M Brewer
  • H G Bartels
  • P H Bartels
  • D Frank
  • R Montironi
  • F Garcia
  • J Davis
  • D S Alberts

Detail Information

Publications3

  1. pmc Green tea compound in chemoprevention of cervical cancer
    Changping Zou
    Guangxi Medical University, Nanning City, China
    Int J Gynecol Cancer 20:617-24. 2010
    ..The selection of nontoxic agents especially food, beverage, and natural products that suppress oncogenic HPV, inhibit malignant transformation, and can additionally be used long term may be important for cervical cancer prevention...
  2. pmc Karyometry in atypical endometrial hyperplasia: a Gynecologic Oncology Group study
    Peter H Bartels
    University of Arizona Cancer Center, Tucson, AZ, USA
    Gynecol Oncol 125:129-35. 2012
    ..About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC)...
  3. ncbi Karyometry in the early detection and chemoprevention of intraepithelial lesions
    J Ranger-Moore
    University of Arizona, P O Box 245024, Tucson, Arizona, AZ 85724 5024, USA
    Eur J Cancer 41:1875-88. 2005
    ..The sensitivity of karyometric detection can help optimise the design of clinical trials of novel chemopreventive agents by decreasing trial duration and/or sample size...