In the normal ectocervix, mitoses are rare and are usually confined to the basal layers. In contrast, they occur more frequently in cervical intraepithelial neoplasia (CIN) and are seen at higher levels, suggesting that CIN may be associated with a progressive dysfunction in proliferative activity of cervical cells. The objective of this study was to use proliferating cell nuclear antigen (PCNA) immunohistochemistry to examine the proliferative activity of cervical epithelial cells in CIN lesions. Sixty- eight cervical biopsies were examined; 20 were totally benign, 14 had CIN I, 21 CIN II, and 13 CIN III. In benign epithelia, PCNA staining was usually confined to the basal layers, whereas in CIN the staining was seen at progressively higher levels of the epithelium. There was a statistically significant correlation between the CIN grade and the highest level of PCNA staining (PCNA grade, r = 0.746, P < 0.001). In addition, the PCNA grade showed significant correlation with the highest level at which mitoses were seen (mitosis grade, r = 0.706, P < 0.001), and a strong direct correlation between the mitosis and CIN grades was also observed (r = 0.955, P < 0.001). These data demonstrate that (1) PCNA immunoreactivity in neoplastic cervical epithelium is different from that seen in the normal cervix, suggesting that CIN is associated with a dysfunctional proliferation of cervical epithelium, (2) that there is a significant correlation between the PCNA grade and CIN grades, and (3) the 'mitosis grades' have a strong correlation with the CIN grades.

Recent advances in whole genome sequencing have led to many discoveries in the mechanisms involved in carcinogenesis. Genomic characterization of premalignant lesions in numerous cancers has led to new prevention strategies, early detection, and treatment options that have saved lives and improved the quality of life for the people suffering from these cancers. Prostate cancer (PCa) is the most common cancer in men in the United States (US) and the second leading cause of death in men from all cancers. However, in African American men (AAM) the mortality rate from PCa is 2.4 times higher than European American men (EAM). In addition, AAM are more likely to get PCa and have a higher PCa burden at diagnosis than their EAM counterparts. This may suggest that there are racial/ethnic differences in the mechanism of carcinogenesis in PCa. PCa and its premalignant lesion, high grade prostatic intraepithelial neoplasia (HGPIN), are one of the most heterogeneous and complex cancers for scientists to determine the mechanisms of carcinogenesis. Due to this complexity, research on HGPIN and PCa has been difficult to carry out and interpret. Projects have been undertaken and progress has been made in the discovery of some genes involved in PCa and potential drivers of initiation, progression and aggressiveness of PCa. However, these studies have mostly been conducted among EAM and have little ethnic diversity. Discovery of new prevention, early detection and treatment methods for PCa will not be possible without advances in the genetic characterization of the pathways of carcinogenesis of PCa among ethnically diverse study populations. To date there are no known genetic characterizations of HGPIN and PCa in AAM. This study aims to characterize chromosomal copy number aberrations (CNA) in paired HGPIN and PCa in AAM. By utilizing advanced microarray techniques, we will determine the degree to which HGPIN and PCa share CNA and identify CNA that may be involved in PCa progression. This study will lay the foundation for future research into CNA that may be used as potential biomarkers for early detection of neoplasms of high-risk for development into PCa in AAM. The discovery of biomarkers and the characterization of the mechanisms involved in PCa progression may lead to treatment options for the prevention of PCa and an overall better outcome for AAM suffering from PCa.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 71-78).

The aim of this research was to study the correlation between tissue tumor marker expression and HR-HPV infection, smoking, hormonal contraceptive use and sex steroids in women with cervical intraepithelial neoplasia or normal epithelium. The study investigated the expression of 11 tumor markers in cervical biopsies obtained from 228 women with different diagnoses ranging from normal cervical epithelium to various stages of CIN. 188 women were recruited at our colposcopy clinic (out-patient surgery, Department of Obstetrics and Gynecology, Falun Hospital) for laser cervical conization or a directed punch biopsy, either because of a vaginal smear (Pap smear) that showed cytological findings suggesting CIN, or because of repeated findings showing atypical squamous cells of undetermined significance (ASCUS). For 40 volunteers, punch biopsies were taken from the normal cervical epithelium. The time period for this study was 2005-2007. Study I :  228 women, of whom 116 were tested, 64 were positive to HR-HPV. The results showed that Ki67 tumor cell proliferation index was the only marker that independently correlated to both the presence of HR-HPV and the severity of cervical lesions. Study II:  228 women, of whom 83 were smokers (36, 9%). Smokers showed lower expression of p53, FHIT (tumor suppressor markers) and interleukin-10 .Higher expression of Cox-2 and Ki-67 (tumor proliferation markers). Study III:  195 women who were premenopausal. There was increased p53 expression (tumor suppressor) in the progestin-IUD users compared to non-users. Decreased IL-10 expression (immunological marker) was observed in both COC users and any progestin-only users. Study IV: Serum from 80 premenopausal women was available. The main finding was that the increased levels of serum progesterone and estradiol were associated with increased Cox-2 expression (proliferation marker). Serum progesterone and estradiol levels influence cellular and extracellular proteins which have been associated with neoplastic development in normal epithelium and CIN. Conclusion: The results of these studies support previous epidemiological findings on the role of smoking, contraceptive use and sex steroids as co-factors in development of CIN and that tumor marker expression varies in different grades of CIN.

High grade intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) are two pathological lesions associated with prostate adenocarcinoma. HGPIN is an architectural finding, while ASAP is a term used to describe a lesion that cannot confidently be diagnosed as prostate adenocarcinoma. The mean incidence rate for HGPIN is 7.7% with a median of 5.2% and range of 0-24.6% and the cancer detection rate mean is 18.1%. The mean incidence rate for ASAP is 5.0% with a median of 4.4% and a range of 0.7-23.4%. The mean cancer detection rate is 40.2%. Currently, the incidence and cancer detection rates for HGPIN and ASAP for Winnipeg, Manitoba, have not been published. A retrospective study was conducted on all prostate biopsies collected from the Manitoba Cancer Care Prostate Centre (MCCPC) from 2008 and 2009. Prostate biopsies with a diagnosis of isolated HGPIN and or ASAP and no previous history of cancer were included in this study. In Winnipeg, Manitoba, from 2008-2009, the mean HGPIN incidence rate was 5.0% and the mean cancer detection rate was 46.1%. The mean ASAP incidence rate was 4.6% and the mean cancer detection rate of 48.2%. As a control, the cancer detection rate following a benign diagnosis was also calculated at 33.3%. The mean incidence and cancer detection rates for HGPIN and ASAP for Winnipeg, Manitoba are slightly lower than literature, but still fall within the published range. In addition, the mean ASAP cancer detection rate is similar to the cancer detection rate following a benign diagnosis indicating that, in our study, both a benign finding and a diagnosis of ASAP hold the same predictive value for cancer on a subsequent re-biopsy.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [79]-87).

Thesis (M.S.)--University of Michigan.

Thesis (M.S.)--University of Michigan.