[Prognostic value of human papilloma virus DNA test in patients surgically treated for squamous cell cervical cancer].

The human papilloma virus (HPV) DNA test was performed in paraffinized biopsy samples of iliac lymph nodes obtained from 98 patients with cervical cancer receiving therapy in N. N. Petrov Research Institute of Oncology in 2000 to 2007. The data obtained was compared to patients clinical course. The HPV DNA was detected in 29 of 98 patients samples (29,6%), 27 of those patients had metastatic disease. These patients had significantly higher metastasis rate than HPV DNA-negative patients (p < or = 0,05). The following highly oncogenic genotypes of HPV DNA were detected: type 16 in 15 patients (51,72%), type 18 in 4 patients (13,79%), type 31 in 5 patients (17,24%) and type 33 in 5 patients (17,24%). In all the cases the HPV type detected in the lymph nodes corresponded to the one detected in the primary tumor. The relapse-free survival of HPV DNA-positive patients with iliac lymph nodes metastases (N1) was significantly lower than in HPV DNA-negative patients (p < or = 0,05). The iliac lymph nodes HPV DNA detection had 43,6% sensitivity (95% CI: 28/60%) and 79,7% specificity (95% CI: 67/89%) for relapse prediction. The test results had diagnostic value in 65,3% of cases, the test was false-negative in 56,4% and false-positive in 20,3% of cases.

[Influence of sodium selenite on carcinogenesis of the prostate and other organs induced by methylnitrosourea and testosterone in rats].

Influence of selenium on induced carcinogenesis of the prostate and other organs was studied in male Wistar rats. Carcinogenesis was induced (68) by using our modification of a combined double-stage model including surgical castration, single administration of N-methyl-N-nitrosourea (MNU) and long-term promotion by a mix of testosterone ethers (MTE). Seven days after MNU injection the rats were randomized to form 2 groups. Controls were fed drinking water while the study group - water containing sodium selenite 4mg/l, daily - till the end of the experiment. Controls (12) were not exposed to any treatment. They were followed up for 55 weeks until sacrificed. Apparent benign prostatic hyperplasia developed in rats subjected to castration, MNU and MTE. Also, such precancerous lesions as prostatic intraepithelial neoplasia (PIN) and prostate cancer including metastatic one were detected. Malignant lymphoma, other than in target tissues, was the most frequent. Prostate pathological changes and lymphomas were not registered in intact rats. Unlike rats treated with MNU and MTE and fed untreated drinking water, selenium did not influence significantly the development of prostate intraepithelial neoplasia but reduced multiplicity of prostate cancer by 44.6%. Simultaneously, the incidence of induced malignant lymphomas decreased by 26.4%.

[Human papilloma virus and lymphatic metastasis in squamous cell carcinoma of the cervix].

Our study included 112 patients with squamous cell cervical carcinoma la-lib stages (FIGO). All of them were restaged on the basis of histological evidence after surgical treatment. Ninety-eight were staged at final analysis. Human papilloma virus (HPV) was detected in endocervical smears and paraffin blocks of lymph nodes by PCR and real-time PCR. Oncogenic HPV in primary tumor was detected in 86 (87.8%); two or more genotypes--65 (75.58%): still more--21 (24.4%). In the latter group, the frequency of regional lymph node metastases was significantly higher. HPV DNA was identified in iliac lymph nodes in 29 (26.6%); 27 of them had metastases to those nodes. HPV in DNA which was significantly more frequent in involved lymphocytes may be used as marker. Since our method for early detection of metastases to regional lymph nodes is highly specific, it may be recommended as a diagnostic procedure.

[Molecular, genetic and immunohistochemical investigation of carcinosarcoma of the female reproductive tract].

Tissue precursors and genesis of female reproductive tract carcinoma vis-a-vis its carcinomatous and sarcomatous patterns remain unknown. To determine the clonal origin of 17 female reproductive tract carcinomas, such molecular, genetic and immunohistochemical techniques as PCR-SSCP and/or denaturing gel electrophoresis for K-ras, p53 and PTEN genes; D17S786, CHRNB1, TP53, BAT26 and BAT40 microsatellites and immunostaining for p53 protein were used. Carcinomatous and sarcomatous components were studied separately. Eight tumors were assumed to be monoclonal (combination or conversion tumors), while one--of an obscure origin. Our results suggest that carcinosarcomas were characterized by chromosomal instability. Moreover, it was shown that it is necessary to combine immunohistochemical techniques with a battery of methods including genetic ones to determine clonal origin of immunologically--stained carcinosarcomas.

[The role of Ki-67, mutant suppressor gene p53 and low mitotic levels in defining the prognosis for adult granulosa cell tumor of the ovary].

Clinico-morphological examination of adult granulosa cell tumors of the ovary was carried out in 17 patients (mean follow-up duration--146.2 +/- 22.16 months). Overall and relapse-free survival appeared significantly higher in low expression of Ki-67 (8.63 +/- 1.4%), mutant suppressor gene p53 (3.55 +/- 1.9%) and low mitotic levels in tumor (2.33 +/- 0.9 per 10 fields of microscope) (p < 0.05).

[Study of the antioxidant drug "Karinat" in patients with chronic atrophic gastritis]. / Izuchenie antioksidantnogo preparata "Karinat" kak sredstva dlia lecheniia bol'nykh s khronicheskim atroficheskim gastritom.

A randomized double blind placebo-controlled trial of the drug karinat was carried out in patients with chronic multifocal atrophic gastritis. Karinat contains beta-carotene 2.5 mg, alpha-tocopherol 5 mg, ascorbic acid 30 mg and garlic powder 150 mg per tablet. Out of 66 patients, 34 received karinat, 32--placebo. Both karinat and placebo were administered for 6 months, one tablet twice a day. Karinat therapy improved digestion, the fibrogastroscopic pattern of mucosa, inhibited Helicobacter pylori infection, stimulated stomach activity, mitigated intestinal metaplasia and interfered with the epithelial proliferation of gastric mucosa. These therapeutic effects were more pronounced in the study group. On the whole, the effectiveness of the drug was significantly higher (29%). Karinat should be recommended for the management of chronic atrophic gastritis, a precursor of stomach cancer.

[Risk of endometrial hyperplasia and carcinoma in breast cancer patients receiving adjuvant tamoxifen]. / Risk vozniknoveniia giperplasticheskikh protsessov i raka éndometriia u bol'nykh rakom molochnoi zhelezy, podvergshikhsia ad''iuvantnomy lecheniiu tamoksifenom.

The antiestrogen drug tamoxifen, which is widely used in adjuvant hormone therapy of breast cancer, presents certain risk of causing hyperplasia and endometrial carcinoma. Our clinical data on 1,969 breast cancer patients (stage I-III) (tamoxifen--947; control--1,022) showed a double rise in endometrial carcinoma risk in cases receiving hormone therapy. Endometrial carcinoma incidence in tamoxifen-treated patients was 3% while in the untreated ones--1.6% (p < 0.05). According to the endometrial tissue study in 439 breast cancer patients, proliferative effect of tamoxifen in the form of endometrial hyperplasia was 5--6 times in tamoxifen users. Meanwhile, endometrial carcinoma and hyperplasia risk increased during a much longer exposure to tamoxifen and in combination with such factors as obesity, diabetes mellitus, uterine myoma and estrogen-type colpocytological response. Hence, breast cancer patients need to undergo dynamic follow-up of the endometrium including ultrasonic examination of the small-pelvis organs and cytological study of ecto- and endocervical smears and endometrial aspirates.

Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer.

OBJECTIVES: To compare estrogen concentrations in endometrial cancer tissue with those in macroscopically normal endometrium and with certain morphological characteristics of the tumor and endocrine parameters in patients. METHODS: The estradiol content was evaluated by radioimmunoassay after homogenization and extraction in 78 adenocarcinomas (61 from postmenopausal patients). RESULTS: Higher concentrations of estradiol in tumor tissue samples than in macroscopically normal endometrium were found in patients of both reproductive and postmenopausal age. This difference was the same in patients with either endometrial carcinoma type I or type II. No association between tumor steroid receptor levels, estradiol concentrations in blood serum, and timing of menopause with intratumoral estradiol contents was discovered. Estradiol concentrations in tumor tissues correlated positively with the clinical stage of disease and rate of tumor invasion (in patients with peripheric/lower type of fat topography), and negatively with tumor differentiation stage (in patients with central/upper type of fat topography) and the percentage of intact double-stranded DNA in normal endometrium. CONCLUSIONS: Tumor estrogen content in endometrial cancer has clinical significance that is modified in the presence of certain endocrine characteristics related to insulin resistance. The role of local estrogen production (aromatase activity) in this setting deserves special study.

[Tumor tissue aromatase and estrogen levels versus clinical course of endometrial cancer]. / Aktivnost' aromatazy, tkanevoe soderzhanie éstrogenov i osobennosti techeniia raka éndometriia.

Levels of aromatase, a key enzyme in estrogen biosynthesis, were assayed in tumor tissue sampled from 25 patients with endometrial cancer. In addition, estradiol concentrations were compared in normal and altered endometrial tissue from 78 patients suffering uterine cancer. Unlike breast cancer, aromatase was not detectable in altered endometrium unless tissue estrogens could be identified in both normal and tumor tissue. Hence, aromatase presence served as an indicator of malignant transformation. Its concentration in samples of uterine tissue varied 0-28.4 fM/mg protein/hr (an average of 12.9(1.7 fM/mg protein/hr). There was hardly any correlation between this level, on the one hand, and menopause and body mass, on the other. Yet, it tended to increase in step with stage of disease and cell differentiation decline. Estradiol concentrations in malignant endometrium in both reproductive and menopausal patients were higher than in macroscopically normal ones, while still cycling women tended to show higher values than menopausal ones. Although there was no significant difference in estradiol levels in the altered endomentrium of patients with pathogenetical patterns of uterine cancer stage I and II, they did show a direct correlation with clinical stage of tumor process and depth of invasion into the underlying myometrium. Hence, unlike estrogens circulating in blood, those contained in tissue ("intratumor") ones did enhance the aggressiveness of endometrial cancer course. It will be for further investigations to show whether it is due to an estrogen fraction being carried away by tumor from the circulation, or estrogens being synthesized by aromatase in tumor itself.

[Frequency of infertility in endometrial cancer]. / Chastota besplodiia pri rake éndometriia.

A retrospective study included 1,559 patients with endometrial carcinoma who had received surgical and combined treatment (1968-1995). It was found that infertility was at the background of practically all cases under the age of 30 (92.3%). Moreover, high rates of infertility were discovered in the histories of patients with light-cell (mesonephroid) carcinoma which developed in menopause.

[Effect of neoadjuvant therapy with neovir on the level of steroid hormone receptors in endometrial cancer tissue]. / Vliiane neoad''iuvantnoi terapii neovirom na soderzhanie retseptorov steroidnykh gormonov v tkani raka tela matki.

The effects of neoadjuvant therapy with neovir, provera and their combinations on endometrial tumor morphology, progesterone (PR) and estradiol (ER) receptor levels were studied in 50 patients, aged 40-78, with primary tumors stage I-III, and without concomitant pathology. A 19-day course of neovir did not alter tumor morphological status but was followed by a significant rise in PR and ER concentrations. After neoadjuvant therapy in combination with provera, which generally lowers cytoplasmic receptor levels, mean values of receptors dropped in PR+ tumors while, in PR- tumors, they increased significantly. Our findings suggest that neovir may be used in clinic to stimulate endometrial tumor sensitivity to specific hormonal therapy, particularly, for hormone-independent neoplasia.

[Peroxidase activity in human uterine tissue: connection with clinico-morphological features of endometrial cancer]. / Aktivnost' peroksidazy v tkani tela matki cheloveka: sviaz' s kliniko-morfologicheskimi osobennostiami raka éndometriia.

Peroxidase activity was determined in 98 patients with endometrial cancers. In 34 patients with endometrial cancers, the activity of the enzyme was also detected in the neighbouring unchanged (normal) tissues. It was shown that in tumor tissues the level of peroxidase activity was higher than in normal ones. The peroxidase activity increased both in tumor and normal endometrium when clinical and morphological characteristics of tumor were unfavourable, i.e. at later stages of the disease, deeper invasion to myometrium, lower levels of differentiation of tumors. The peroxidase activity was somewhat higher in post-menopausal women; however, no direct was found between the activity of this enzyme in malignant and normal tissues, on the one hand, and the menstrual status of patients with different clinical and morphological characteristics of endometrial cancer, on the other relationship. The level of peroxidase activity in normal and malignant tissues was more pronounced in advanced and poorly-differentiated tumors. It seems important to use peroxidase activity as a prognostic factor and as a possible marker of endometrial cancer hormone-dependence that needs further investigation.