The goals of this project are to improve our understanding of carcinogenesis in gynecologic cancers and to enhance diagnostic and prognostic accuracies using quantitative analyses. During the past year, a close relationship between human papillomavirus infection (genital warts, condylomas) and cervical intraepithelial neoplasias (squamous dysplasias and carcinomas in situ) has been confirmed by nuclear DNA quantitation, immunoperoxidase stain for human papillomavirus capsid antigens, and morphologic analyses. Using these techniques, it is possible to demonstrate a transition from cervical condyloma to neoplasia. This occurrence is supported by the coexistence of papillomavirus capsid antigens and aneuploid DNA patterns in 14% of cervical condylomatous lesions. The risk of developing cervical intraepithelial neoplasia is increased in flat rather than exophytic condylomas, and in condylomas with moderate as compared to mild degree of nuclear atypia. These findings support the recent molecular hybridization studies indicating that several types of human papillomaviruses with different oncogenicities exist in the female genital tract. In 51 patients with clinical stage I or II cervical adenocarcinoma, the survival is most reliably predicted by the standard deviation of nuclear size (p=0.002), the DNA ploidy level (p=0.003), the clinical stage (p=0.0072), the percentage of glandular lumen (p=0.0074), the mean nuclear size (p=0.04), and the histologic grade (p=0.09). These findings demonstrate that the prognostic accuracies can be improved by quantitative analyses over the routine histologic examinations. (3)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034870-04
Application #
3172687
Study Section
Pathology B Study Section (PTHB)
Project Start
1982-09-01
Project End
1989-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Huang, S J; Cheng, L; Lewin, K J et al. (1991) Immunohistochemical estrogen receptor assessment in hyperplastic, neoplastic, and physiologic endometria. Pathol Res Pract 187:487-95
Zeng, Q S; Fu, Y S; Cochran, A J (1990) Nuclear DNA measurements of metastatic melanoma by a computerized digital imaging system. Hum Pathol 21:1112-6
Fu, Y S; Cheng, L; Huang, I et al. (1989) DNA ploidy analysis of cervical condyloma and intraepithelial neoplasia in specimens obtained by punch biopsy. Anal Quant Cytol Histol 11:187-95
Gupta, J W; Saito, K; Saito, A et al. (1989) Human papillomaviruses and the pathogenesis of cervical neoplasia. A study by in situ hybridization. Cancer 64:2104-10
Sagae, S; Berek, J S; Fu, Y S et al. (1988) Peritoneal cytology of ovarian cancer patients receiving intraperitoneal therapy: quantitation of malignant cells and response. Obstet Gynecol 72:782-8
Fu, Y S; Huang, I; Beaudenon, S et al. (1988) Correlative study of human papillomavirus DNA, histopathology and morphometry in cervical condyloma and intraepithelial neoplasia. Int J Gynecol Pathol 7:297-307
Fu, Y S; Berek, J S (1988) Minimal cervical cancer: definition and histology. Recent Results Cancer Res 106:47-56
Fu, Y S; Ferenczy, A; Huang, I et al. (1988) Digital imaging analysis of normal, hyperplastic and malignant endometrial cells in endometrial brushing samples. Anal Quant Cytol Histol 10:139-49
Shibata, D; Fu, Y S; Gupta, J W et al. (1988) Detection of human papillomavirus in normal and dysplastic tissue by the polymerase chain reaction. Lab Invest 59:555-9
Fu, Y S; Berek, J S; Hilborne, L H (1987) Diagnostic problems of in situ and invasive adenocarcinomas of the uterine cervix. Appl Pathol 5:47-56

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