Potential role of the inactivated X chromosome in ovarian epithelial tumor development.

BACKGROUND: Ovarian epithelial tumors can be divided into subcategories often regarded as different stages of neoplastic transformation. Cystadenomas belong to the least aggressive subgroup and are noninvasive and nonmetastatic. Ovarian tumors of low malignant potential (LMP) are intermediate between cystadenomas and carcinomas and show markedly reduced invasive and metastatic abilities. Invasion and metastasis are the hallmarks of carcinomas, which constitute the most aggressive subgroup and can be further subdivided into different grades. PURPOSE: We performed comparative allelotype analyses of ovarian cystadenomas, LMP tumors, and carcinomas, reasoning that such analyses could provide clues about the molecular determinants of their phenotypic differences. Because we realized that allelic losses involving the X chromosome might be associated with LMP tumor development, we determined whether such losses were interstitial and whether they involved the active or the inactive X chromosome. METHODS: Frequencies of loss of heterozygosity (LOH) at specific loci in every chromosomal arm were determined in 16 ovarian cystadenomas, 23 ovarian LMP tumors, 15 low-grade ovarian carcinomas, and 35 high-grade ovarian carcinomas by use of either the polymerase chain reaction (PCR) or Southern blot analyses. We took advantage of the fact that DNA methylation is an important mechanism of X-chromosome inactivation to determine whether losses involving the X chromosome were in the active or the inactive copy. We analyzed the methylation status of retained alleles on the X chromosome by determining whether they could be amplified by PCR after digestion with the methylation-sensitive restriction endonuclease Hpa II. RESULTS: High-grade carcinomas contained frequent(>50%) LOH in four autosomal chromosome arms, i.e., 6q, 13q, 17p, and 17q. Except for 13q, these same chromosomal arms showed frequent LOH in low-grade carcinomas. LOH in autosomal chromosomes was comparatively rare in LMP tumors and was absent in cystadenomas. In contrast, half (eight of 16) of LMP tumors informative for a locus in the proximal portion of chromosome Xq showed LOH at that locus. These losses were the result of interstitial deletions in six of the eight cases and involved the inactive copy of the X chromosome exclusively. Similar losses in the X chromosome were not seen in either cystadenomas or low-grade carcinomas. CONCLUSIONS AND IMPLICATIONS: LOH at multiple loci is associated with the development of ovarian carcinomas but not with the development of cystadenomas and LMP tumors. However, the integrity of a locus in chromosome Xq that possibly escapes X-chromosome inactivation is important for the control of LMP tumor development. The fact that this locus does not appear to be involved in the genesis of low-grade carcinomas suggests that LMP tumors are not precursors of such carcinomas.

Indications, techniques, and advantages of partial laser vaginectomy.

Partial vaginectomy is seldom used diagnostically to evaluate vaginal neoplasia because of its technical difficulty, the possible need for grafting, and postoperative vaginal agglutination or stenosis. We found that use of the carbon dioxide laser simplified vaginectomy in ten subjects, producing a low rate of complications, an excellent diagnostic specimen, and superior healing.

The relationship between pain and uterine contractions during laser vaporization of the cervix.

Laser vaporization of the uterine cervix to treat cervical dysplasia is usually described by patients as moderately painful. Many describe the pain as uterine cramping, but most authorities attribute the pain to heat buildup during the procedure. To specify the mechanism of pain, intrauterine pressures were measured in 16 subjects (randomly divided into placebo and control groups of eight each) before and during cervical laser vaporization for dysplasia. The women were told what to expect during intrauterine pressure recording and laser vaporization and that a study of pain medication during laser vaporization was being conducted. The session began with 5 minutes of baseline intrauterine pressure recording. Subjects were then randomly given oral placebo or ibuprofen, 600 mg. Thirty to 45 minutes later, the intrauterine catheter was reinserted and the pressure recorded during 5 minutes of cervical laser vaporization. Laser vaporization increased significantly the frequency (P less than .025) and amplitude (P less than .03) of contractions in the placebo group but not in subjects given ibuprofen. However, post-procedure pain questionnaires showed no difference in pain perception between the groups. This study shows that pain during laser vaporization of the cervix is not due to increased uterine contractions, and that pain was not significantly relieved by ibuprofen.

Improving the Cytobrush as an aid in the evaluation of the abnormal Papanicolaou test.

In a series of 39 patients undergoing cervical conization, the Cytobrush was used to determine whether dysplasia involved the endocervical canal. To improve the specificity of the Cytobrush for this purpose, a sleeve was designed to guide the brush into the endocervical canal in order to minimize contamination from ectocervical lesions. Both the unsleeved and sleeved Cytobrush demonstrated good sensitivity for detecting dysplasia within the endocervical canal (89 and 95%, respectively). The sleeved Cytobrush demonstrated greater specificity than the unsleeved Cytobrush (90 versus 60%; P less than .05). Compared with endocervical curettage, the Cytobrush used in conjunction with the described "cytosleeve" offers an inexpensive, less painful, and accurate method of determining endocervical involvement of dysplasia.

Genital tuberculosis: case report and literature review.

A 64-year-old woman complained of abdominal pain and postmenopausal bleeding. A uterine curettage demonstrated acid fast bacilli and non caseating granulomas, indicating Mycobacterium tuberculosis. A chest roentgenogram revealed the presence of bilateral upper lobe calcific granulomas. The epidemiologic, diagnostic, and therapeutic implications of genital tuberculosis are discussed.