No abstract

Ovarian tumors of low malignant potential ("borderline tumors") have been proposed variably to represent a distinctive type of malignancy, precursors of frank ovarian malignancy, or a nonmalignant process. We analyzed 81 malignant and 39 borderline ovarian tumors for p53 immunoreactivity and alterations in codon 12 of Ki-RAS in order to correlate these alterations with tumor and cell type. Diffuse p53 immunoreactivity was significantly more prevalent among malignant (36 of 81, 44%) than among borderline (3 of 39, 8%) tumors and was particularly prevalent among serous invasive carcinomas (16 of 26, 62%). Conversely, mutations in codon 12 of Ki-RAS were significantly more prevalent in borderline (16 of 39, 41%) than in malignant (9 of 81, 11%) ovarian tumors and were most prevalent among mucinous tumors. This preliminary molecular analysis suggests that serous borderline tumors have some molecular features usually associated with malignancy but are unlikely to represent a precursor of invasive serous carcinoma. In contrast, mucinous borderline tumors may represent a precursor or variant of mucinous carcinoma of the ovary.

Metaplasia of subcoelomic mesenchyme has been implicated, but not proven, in the pathogenesis of common gynecological diseases such as endometriosis and rarer entities such as leiomyomatosis peritonealis disseminata and gliomatosis peritonei (GP). GP is associated with ovarian teratomas and is characterized by numerous peritoneal and omental implants composed of glial tissue. Two theories to explain the origin of GP have been proposed. In one, glial implants arise from the teratoma, whereas in the other, pluripotent Müllerian stem cells in the peritoneum or subjacent mesenchyme undergo glial metaplasia. To address the origin of GP, we exploited a unique characteristic of many ovarian teratomas: they often contain a duplicated set of maternal chromosomes and are thus homozygous at polymorphic microsatellite (MS) loci. In contrast, DNA from matched normal or metaplastic tissue (containing genetic material of both maternal and paternal origin) is expected to show heterozygosity at many of these same MS loci. DNA samples extracted from paraffin-embedded normal tissue, ovarian teratoma and three individual laser-dissected glial implants were studied in two cases of GP. In one case, all three implants and normal tissue showed heterozygosity at each of three MS loci on different chromosomes, whereas the teratoma showed homozygosity at the same MS loci. Similar results were observed in the second case.

In mouse models and humans, Helicobacter pylori is associated with an increase in serum gastrin and gastrin-expressing (G) cells with a concomitant decrease in somatostatin-expressing D cells. Inflammation of the gastric mucosa can progress to metaplastic changes in the stomach and to decreased colonization by H. pylori and increased colonization by non-H. pylori organisms. In addition, about 20% of individuals with chronic gastritis are H. pylori negative, suggesting that other organisms may induce gastritis. Consistent with this hypothesis, we report here that Acinetobacter lwoffii causes the same histologic changes as does H. pylori. Gastric epithelial cells were isolated from the entire stomach by an enzymatic method for quantitation by both flow cytometry and morphometric analysis. Two months after mice were inoculated with H. pylori or A. lwoffii, the mucosal T-and B-cell numbers significantly increased. Helicobacter pylori causes chronic atrophic gastritis, and its presence is correlated with the development of peptic ulcer disease and gastric adenocarcinoma (19,25,27). However, there is also an association between colonization of the stomach by non-Helicobacter organisms and chronic atrophic gastritis (7,9,30). Approximately 25% of gastric cancer patients have no evidence of previous or current H. pylori infection based on serology (12). In addition, during long-term acid suppression, the presence of H. pylori and that of non -H. pylori bacteria are independent risk factors for the development of atrophic gastritis (29). Studies of several animal models and humans have clearly shown that bacteria are important in triggering mucosal damage and inflammation in the stomach (15,20,42). In addition, under hypochlorhydric conditions it is known that bacterial overgrowth by non-Helicobacter organisms triggers perturbations in the neuroendocrine and epithelial cell populations (42). The implications are that the pathology observed may not be specific for H. pylori but instead is the general response of the gastric mucosa to colonization by bacteria.H. pylori is characterized by its ability to survive in the low-pH milieu of the stomach by generating an alkaline microenvironment. With reduced levels of acid (hypochlorhydria or achlorhydria), the competitive niche established by H. pylori dissipates and the human stomach becomes susceptible to colonization by other organisms (9, 18). Gastric colonization by gram-negative bacteria other than H. pylori is common in intensive care unit patients, who often have an alkaline gastric pH due to routine treatment with antacids, proton pump inhibitors, and histamine 2 receptor antagonists. Antiulcer medications are known to increase the gastric pH and permit colonization of the stomach by opportunistic pathogens, such as Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas spp., believed to contribute to the development of nosocomial pneumonia (8,36). Patients with pernicious anemia are colonized by organisms other than H. pylori and develop atrophic gastritis an...