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Background: The human ovarian surface epithelium (HOSE) is the putative source of ovarian epithelial cancer, the most lethal gynecologic malignancy that affects women in the United States. The current study was designed to provide a database of normal HOSE cell features for diagnostic and research applications., Methods: HOSE was harvested from 42 women undergoing laparoscopy or laparotomy for benign gynecologic disorders, infertility problems, or pregnancy. Of the 42 women, 12 were postovulatory and 20 were receiving hormonal regimens. Cells were harvested with a sterile brush inserted through a laparoscopic port or with a sterile cell scraper at laparotomy., Results: Two HOSE populations were identified, ranging in size from 8 to 10 microm and from 15 to 20 microm, respectively. The cells measuring 15-20 microm exhibited slight anisonucleosis, more prominent nucleoli, fine cytoplasmic metachromasia, and an overall reparative or squamoid morphology. Cells were single or arranged in small clusters, sheets, or papillae. They coexpressed cytokeratin and vimentin but did not overexpress p53. Cellularity and proliferation (up to 3.2% +/- 0.8) were higher and papillae more frequent in postovulatory and cyst-bearing ovaries, including polycystic ovaries, suggesting underlying ovarian or hormonal influences. Representative HOSE brushings yielded a mean of 23,133 cells per patient (range, 4250-64,500 cells), equivalent to an estimated 0.58, 0.46, and 0.14 microg of nuclear protein, cell RNA, and nuclear DNA, respectively. Within 7-10 days of explantation, HOSE cells formed confluent monolayers with immunohistochemical and ultrastructural epithelial features., Conclusions: The current study defined baseline features of HOSE cells important to pathologists and clinicians evaluating women at risk for ovarian epithelial cancer and to researchers investigating the pathobiology of this aggressive gynecologic malignancy., (Copyright 2003 American Cancer Society.)

Argyrophilic nucleolar organizer regions (AgNOR) have been correlated with proliferative activity of neoplasms. Increased AgNOR may reflect increased proliferative activity of cells or ploidy. To explore this hypothesis, 41 breast carcinomas were processed for AgNOR silver staining and DNA flow cytometry. AgNOR counts were expressed as mean AgNOR/nucleus and percentage of tumor cells with more than five AgNOR/nucleus. The first count was designated mean AgNOR or mAgNOR, and the second count was designated AgNOR proliferative index or pAgNOR. Using Mantel-Haensel statistical analysis, carcinomas that exhibited mAgNOR of 2.4 or more had a high likelihood of aneuploidy (P less than 0.0001), an S-phase fraction of more than 5.8% (P less than 0.003), or a diameter greater than 2 cm (P less than 0.007). In addition, tumors with pAgNOR of 8% or more showed a statistically significant correlation with aneuploidy (P less than 0.004), tumor grade (P less than 0.04), and a more significant one with high S-phase fraction (P less than 0.0001). No significant correlation was obtained between pAgNOR and tumor size or lymph node status. These data indicate that AgNOR quantitation reflects changes in DNA ploidy and cell proliferation. They also suggest that the mean AgNOR counts correlate best with the DNA mass or ploidy and that the frequency of cells with higher AgNOR count best reflects proliferative activity or S-phase fraction.

A retrospective study of testicular histology was carried out in 21 prepubertal boys and in 11 intrapubertal or postpubertal boys who died from 1 day to 1 year after treatment with chemotherapy (CT) with or without radiation therapy (RT) for extragonadal solid tumors. Based on autopsy findings, profound histologic changes were found in six prepubertal boys and in all but one of the intrapubertal and postpubertal boys. For three of the prepubertal and five of the postpubertal boys with altered testicular histology, the contribution of pelvic RT could not be excluded. When prepubertal patients were evaluated according to nutritional status, a thickened tubular wall and absent or severely reduced spermatogonia were found in only 1 of 11 adequately nourished boys as compared with 5 of 10 malnourished boys. In intrapubertal and postpubertal boys, the tubular wall was thickened in six and these changes were independent of nutritional status. All malnourished intrapubertal and postpubertal patients demonstrated impaired spermatogenesis (versus 67% of age-matched malnourished controls), whereas similar impairment was noted in 60% with adequate nutrition versus 20% of controls. The diffuse damage of germ cells and tubules in malnourished younger boys suggests that the prepubertal male is not necessarily protected against the reproductive effects of cancer therapy.

The gonadal histology of 21 prepubertal, intrapubertal, and postpubertal girls who died 1 day to 2 months after cessation of therapy for extragonadal solid tumors was reviewed. In addition to focal or diffuse cortical fibrosis, a reduction in follicle numbers and impaired follicular maturation were observed in cancer patients independent of their pubertal age. These changes appeared to be more severe in malnourished patients and in girls who received multiple agent chemotherapy, with or without irradiation. Both before and after the age of 10 years, most cancer patients had a total number of follicles similar to that of age- and nutrition-matched controls. However, the majority of these girls displayed impaired follicular maturation as demonstrated by reduced numbers of growing and antral follicles compared to controls. Histologic evidence of ovarian damage suggests that the future reproductive performance may be impaired in some female cancer patients treated even before puberty.