Expression of p53 protein in the endometrial polyp in postmenopausal women.

OBJECTIVE: To evaluate p53 protein expression in the endometrial polyp and compare with adenocarcinoma and atrophic endometrium of postmenopausal women. MATERIALS AND METHODS: Ninety-eight postmenopausal women were included in this study and divided into three groups related to histopathologic diagnosis: Group A--endometrial adenocarcinoma (n = 40), Group B--endometrial polyp (n = 38), and Group C--endometrial atrophy (n = 20). The length of this study was from 1990 to 2004. The endometrial samples were collected from hysteroscopic biopsy or surgery then processed for histopathologic routine. One thousand cells of each histological section were evaluated for immunohistochemical analysis using p53 antibodies. The ANOVA test was performed for the statistical analysis. RESULTS: The expression of p53 in adenocarcinoma samples was the highest. The expression of polyp was positive when associated to hyperplasia without atypia. All samples of atrophic endometrial were negative. CONCLUSIONS: The present data suggested that presence of hyperplasia in the endometrial polyp is factor to increase the expression of p53.

Sentinel lymph node in endometrial cancer.

The aim of this study was to evaluate the possibility of identifying the sentinel lymph node and involvement of neoplastic cells in patients with endometrial carcinoma limited to the uterus, and also its correlation with the conditions of other pelvic and para-aortic lymph nodes. Forty patients with endometrial carcinoma, clinical staging I and II, were submitted to complete surgical staging through laparotomy, as recommended by FIGO in 1988. The sentinel node was investigated using patent blue dye in the myometrial subserosa. The sentinel node was excised and submitted to frozen section examination of specimen, stained with hematoxylin and eosin (H&E). Afterward, selective bilateral para-aortic and pelvic lymphadenectomy, total hysterectomy with bilateral salpingo-oophorectomy were performed. The lymph nodes excised were examined by means of paraffin-embedded slices stained with H&E and of imunohistochemistry with antikeratin antibody AE1/AE3. The sentinel lymph node was identified in 77.5% of patients (31/40), and 16.1% (5/31) presented neoplastic involvement in the node. In 25 cases of negative sentinel node, 96% (24/25) had no neoplastic involvement, and 4% (1/25) had other lymph node affected (false negative). In nine cases with no sentinel node identified, 55.5% (5/9) had lymph node involvement. The results of this study allow us to conclude that it is possible to identify the sentinel node using the methods described, and the pathologic examination significantly represents the same conditions of other pelvic and para-aortic lymph nodes.

Progesterone receptor (PROGINS) polymorphism and the risk of endometrial cancer development.

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in São Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The chi(2) test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.

Differential gene expression profile reveals overexpression of MAP3K8 in invasive endometrioid carcinoma.

Gene microarray technology is highly effective in screening for differential gene expression and has hence become a popular tool in the molecular investigation of cancer. In the present study, cDNA microarrays containing 2,000 different genes were used to analyze gene expression profiles in ten human postmenopausal endometrioid-paired carcinoma specimens versus corresponding adjacent normal tissue to identify differentially expressed genes. In our study several genes were found differentially expressed. One of them was the MAP3K8, a gene that has never been described to be overexpressed in this kind of malignancy. To validate the differential expression of this gene as well as the membrane array, we performed semiquantitative reverse transcription-PCR analysis. MAP3K8 was found overexpressed in 30% of the endometrial carcinoma samples. To the best of our knowledge this is the first report showing the MAP3K8 oncogene linked to human endometrial carcinoma suggesting that it may be another molecule involved in human endometrial cancer.

Ultrasonographic and morphological studies of the postmenopausal endometrium using unopposed estrogen replacement therapy with regular pause: a prospective preliminary study.

UNLABELLED: Hormone replacement therapy with progestogen is known to have severe side effects or complications in certain patients. OBJECTIVE: The goal of this study is to evaluate the safety and efficacy of an alternative treatment regimen with a mensal pause using both transvaginal sonography (TVS) and endometrial biopsy to follow patients. METHODS: A total of 30 postmenopausal women were treated with unopposed estrogen for 21 days each month followed by a regular pause of 9-10 days, and were studied prospectively for 18 months. The TVS measurements of endometrial thickness and biopsy of the endometrium were done on the 21st day of treatment and the 7th day of the pause at 6-month intervals throughout the study. RESULTS: There was a significant decrease of proliferative activity at all three time points during the study (6, 12 and 18 months) when tested on the 7th pause day (PD7). The percentage of patients with hyperplasia without nuclear atypia and endometrial thickness > or =8mm was 32% at 6 months, but decreased to 22 and 19% at 12 and 18 months, respectively. All cases of hyperplasia regressed after the hormonal pause throughout the treatment period. CONCLUSIONS: This study presents an alternative treatment regimen for select patients having side effects or complications from progestogen administration; however, studies evaluating the safety and efficacy of this regimen over longer time periods are necessary.

Hysteroscopic evaluation of the endometrium of post-menopausal patients with breast cancer before and after tamoxifen use.

OBJECTIVE: To evaluate by hysteroscopy and histopathology the influence of tamoxifen in the endometrium of post-menopausal women with previous breast cancer. METHOD: Out of 46 patients studied, 20 of them had been using tamoxifen for an average length of 12 months, and are still being followed-up. Hysteroscopy with endometrial biopsy was performed before and after the use of the drug. RESULTS: The prevalence of endometrial activity before and after this hormoniotherapy was the same, i.e. 10.0%, showing a non-significant variation. CONCLUSION: The hormoniotherapy with tamoxifen has not increased the endometrial proliferactive activity of postmenopausal patients with breast cancer. The most common hysteroscopical finding was numerous vesicles disseminated throughout the uterine cavity probably due to atrophy of the endometrium.

[A hysteroscopic and anatomicopathological study in women with breast cancer]. / Studio isteroscopico e anatomopatologico in donne con cancro della mammella.

OBJECTIVE: To study the uterine mucosa of women with breast cancer in order to evaluate the frequency of endometrial diseases. EXPERIMENTAL DESIGN: Prospective, controlled study carried out from January to December 1996. SURROUNDINGS: Patients with breast cancer and normal controls from 4 out-patient university services in Porto Alegre, Brazil. PATIENTS: Postmenopausal women without hormonal therapy were compared: 67 of them with breast cancer and 101 normal controls. METHODS: Hysteroscopy followed by endometrial biopsy carried out in both groups as an out-patient procedure. RESULTS: In patients with breast cancer, 29.85% abnormal biopsies were found as follows: 10 endometrial polyps (15.0%), 8 with proliferative changes (11.9%), 1 case of cancer (1.5%), and one case of hyperplasia (1.5%). In the control group 8% abnormal morphological findings were found, as follows: 4 (4%) with endometrial polyps and 4 (4%) with proliferative changes. The differences in abnormal biopsies were statistically significant, mainly in patients with corporal mass index above 27.3. The sensibility of hysteroscopy was 82.14%; its specificity 97.16%; its predictive positive value 85.18% and its predictive negative value 96.48% in detecting endometrial activity, for a prevalence of 16.7% of endometrial activity. CONCLUSIONS: Endometrial evaluation must be included in the initial evaluation of patients with breast cancer, mainly if they were obese. Hysteroscopy, performed in out-patient basis, showed to be an adequate method to evaluate the uterine mucosa, helping to select the area of this cavity for biopsy.

Peritoneal borderline cystoadenocarcinoma.

Carcinomas of peritoneal origin represent a seldom diagnosed entity of unknown etiology, with important implications in terms of prophylactic oophorectomy. Initially described in patients belonging to families at high risk for ovarian cancer, it possibly has a pathogeny similar to that of endosalpingiosis and of some cases of endometriosis. We report a case of peritoneal borderline mucinous carcinoma with an anatomopathological diagnosis of normal ovaries.

Transvaginal ultrasonography and the progestogen challenge test in postmenopausal endometrial evaluation.

OBJECTIVE: To analyze the morphologic and ultrasonographic aspects of the endometrium of postmenopausal women according to the progestogen challenge test. METHODS: The study was conducted on 150 postmenopausal women. Each patient was submitted to transvaginal ultrasonography for measurement of endometrial echo thickness and to endometrial biopsies, followed by the progestogen challenge test. RESULTS: Women with a negative test presented atrophic endometrium in 94% of cases. The other 6% have shown active endometrium, but none had hyperplasia. However, 56% of the patients with a positive test had atrophic endometrium. There was a correlation between endometrial thickness less than 5 mm and endometrial atrophy in patients with either positive or negative tests. CONCLUSION: Because the progestogen challenge test is cheap and easy to deal with, it can be done as a primary screening method in asymptomatic postmenopausal women. If the test is positive, ultrasonography is required in order to determine who needs a more accurate examination of the endometrium. If the test is negative, ultrasonography is not required due to the great number of women who have atrophic endometrium.

Importance of peniscopy, oncologic cytology and histopathology in the diagnosis of penile infection by human papillomavirus.

INTRODUCTION: Male genital infection by human papillomavirus is of particular importance since it is often asymptomatic. The patient generally presents no clinical lesion. Therefore, men represent an important reservoir of virus, playing a special role in the transmission and perpetuation of the disease. PATIENTS AND METHODS: In the present prospective clinical trial study, 190 sex partners of women with genital infection by human papillomavirus, associated or not with cervical intraepithelial neoplasia, were investigated. All patients were unaware of or denied the presence of a genital lesion. RESULTS: Cytologic examination revealed koilocytosis in 9 cases (4.7%) in the urethra and in 3 cases (1.6%) in the corona of the glans and the distal prepuce. Peniscopy with the previous use of 5% acetic acid revealed white lesions in 97.9% of the patients. Toluidine blue stained most of the lesions. At least one fragment revealed koilocytosis in the histopathologic study of 97 cases (51.05%). CONCLUSION: The three methods complement one another, allowing a more precise diagnosis of the infection in men.

Transvaginal ultrasound, uterine biopsy and hysteroscopy for postmenopausal bleeding.

OBJECTIVES: To determine the importance of endometrial biopsy and transvaginal ultrasound in patients with postmenopausal bleeding. METHODS: Eighty patients with postmenopausal bleeding were submitted to transvaginal ultrasound followed by endometrial biopsy. Hysteroscopy and dilatation and curettage were carried out to confirm normality of the uterine cavity. RESULTS: The endometrial echo could be visualized in all patients with postmenopausal bleeding. The biopsy failed to detect one case (1.38%) of adenocarcinoma and 14 cases (17.5%) of endometrial polyps. The sensitivity in detecting endometrial malignancy was 94.44% for endometrial biopsy and 100% for transvaginal ultrasound, when the endometrial thickness was more than 8 mm. CONCLUSIONS: When the thickness of the endometrial echo is less than 3 mm there is no need for anatomopathologic investigation. When this limit was adopted, all cases were associated with endometrial atrophy, and when the limit was 4 mm or more, active endometria were detected, requiring further histopathologic investigation by hysteroscopy and directed biopsies. Above 8 mm, malignancy may be found.

The progestogen challenge test in postmenopausal women: clinical and morphologic aspects.

The clinical aspects and anatomopathological patterns of 150 postmenopausal women were studied using the progestogen challenge test. An endometrial biopsy was obtained and submitted to the progestogen test. A histopathological analysis of the uterine mucosa from women with a positive progestogen test revealed that the endometrium was active in 44 percent of cases and atrophic or inactive in 56 percent. In contrast, among women with a negative response, the endometrium was atrophic in 94 percent of cases and active in 6 percent. Analysis of clinical aspects did not show significant differences between groups in terms of age; age at menarche and at menopause; fasting blood glucose levels; or body mass. However, postmenopausal time was significantly shorter for women with a positive test, with a correlation between postmenopausal time of one to two years and test positivity. The progestogen challenge test for the detection of atrophic endometrium presented 78.57 percent sensitivity, 77.05 percent specificity, 44 percent positive predictive value, and 94 percent negative predictive value. Thus, when negative, the test is highly valuable, indicating the presence of atrophic endometrium in 94 percent of cases. False-negative results occurred in only 6 percent of the subjects, with no case of hyperplasia detected. However, when the response to the test was positive, the endometrium was atrophic in 56 percent of the cases. We suggest that, in order to avoid invasive procedures, the progestogen challenge test be combined with other methods such as transvaginal ultrasonography.

Ultra-sonografia seriada do endométrio e da endocérvice durante o ciclo menstrual normal da mulher / Serial ultrasonography of the endometrium and endocervix during the normal menstrual cycle of women

Os relatos ultra-sonográficos do endométrio humano säo, em sua maior parte, obtidos de pacientes com esterilidade conjugal, nulíparas, fazendo uso de drogas indutoras da ovulaçäo. Essas pesquisas, geralmente, näo se acompanham do estudo histológico da cavidade uterina e preocupam-se, sobretudo, com o período ovulatório. Há, contudo, controvérsias na interpretaçäo das imagens. OBJETIVO. Estudas a ultra-sonografia do endométrio, no decorrer do ciclo menstrual normal. MÉTODOS. Os autores selecionaram 15 mulheres, eumenorréicas, multíparas, que näo faziam uso de drogas indutoras da ovulaçäo, DIU ou contra-conceptivos hormonais. todas foram examinadas no primeiro, no sétimo, no décimo-quarto eno vigésimo-primeiro dia do ciclo menstrual. Confrontaram-se os achados ecográficos com os resultados histológicos. RESULTADOS. Avaliaram a imagem ultra-sonográfica do endométrio em 66.66 por cento das mulheres no primeiro dia do ciclo. Em todas elas, no sétimo, décimo-quarto e vigésimo-primeiro dia essa imagem também pôde ser identificada e apreciada. Verificaram, durante o ciclo, aumento progressivo da espessura da imagem endometrial, de forma linear. O halo hipoecóico teveincidência progressiva, atingindo 93,33 por cento no vigésimo-primeiro dia do ciclo. CONCLUSÄO. As alteraçöes cíclicas do endométrio foram demonstradas pela ultra-sonografia. As modificaçöes endocervicais também foram detectadas. Todavia, säo menos exuberantes do que as observadas no endométrio

Menopausal genuine stress urinary incontinence treated with conjugated estrogens plus progestogens.

OBJECTIVE: The aim of the study was to investigate clinically and urodynamically the effects of hormonal replacement in the treatment of genuine stress urinary incontinence in postmenopausal females. METHODS: Clinical and urodynamic variables of 30 postmenopausal women with genuine stress urinary incontinence were evaluated after 3 months' treatment with conjugated estrogens plus progestogens. Urodynamic evaluations were performed in all patients before and after treatment. RESULTS: Forty-six percent of the patients treated medically were judged to be cured and 43% were judged to be markedly improved. Maximum urethral closure pressure, maximum cystometric capacity and mean flow were significantly increased. Residual urine and diurnal and nocturnal voluntary micturition were markedly decreased (P < 0.05). CONCLUSION: We conclude that hormone replacement in the form of conjugated estrogens plus progestogens results in the clinical and urodynamic improvement of genuine stress urinary incontinence in postmenopausal women.

[Serial ultrasonography of the endometrium and endocervix during the normal menstrual cycle in women]. / Ultra-sonografia seriada do endométrio e da endocérvice durante o ciclo menstrual normal da mulher.

Articles on ultrasound of the human endometrium are in the majority of the cases based on studies of patients who have infertility and are taking drugs to induce ovulation. Such investigations do not include histological study of the endometrium and have focused on the ovulatory period. There is controversy in the interpretation of the images. PURPOSE--To evaluate the sonographic appearance of the endometrium during the normal menstrual cycle. METHODS--We studied 15 multiparous women with normal cycles, and who were not under drugs for ovulation induction, had neither IUD, nor were having oral hormonal contraceptives. They were seen on the first, seventh, fourteenth, and twentieth-first days of the menstrual cycle. The sonographic aspects were compared with the histological findings. RESULTS--We could see the images of the endometrium on the first day of the cycle in 66.66% of the patients. On the other visits we could study properly its features very well in all the patients. The endometrial image thickness increased in a linear pattern and the hypoechogenic halo was seen in 93.33% of the patients on the twentieth-first day of the menstrual cycle. CONCLUSION--The cyclic changes of the endometrium were shown with the sonography. The cyclic changes of the endocervix were evaluated too with the sonogram although they are not as remarkable as the endometrial ones.

Patologia associada ao leiomioma uterino: revisäo de 600 casos / Pathology associated with uterine leiomyoma: review of 600 cases

Foram analisadas 600 pacientes com leiomioma uterino (LU), atendidas na Escola Paulista de Medicina, que se submeteram a terapêutica cirúrgica entre 1976 e 1987. O exame histopatológico das peças cirúrgicas confirmou a presença de neoplasia benigna e, na maioria das vezes, surpeendeu outras patologias associadas. Estudaram-se também, como grupo controle, 150 úteros (de histerectomias), procurando-se conhecer a freqüência dessas entidades patológicas associadas em näo portadoras de LU. As principais associaçöes encontradas foram: cervicite crônica, adenomiose, cistos foliculars, alteraçöes tubárias - congestäo, edema e processo inflamatório -, pólipos uterinos, hiperplasia endometrial, endometriose, neoplasias do ovário e do endométrio. A coexistência dessas condiçöes patológicas ocorreu em 71,17% dos casos. O leiomioma é a neoplasia mais freqüente do útero e da pelve (18,19). A coexistência do tumor com outras entidades patológicas é pouco citada na literatura, assim como suas possíveis inter-relaçöes. Por causa da alta freqüência do leiomioma na populaçäo, poder-se ia associa-lo, apenas de forma fortuita, a outras entidades nosológicas do trato genital. Interessados em saber se haveria patologias secundárias ao leiomioma ou coexistência meramente casual, e também se as associaçöes teriam o mesmo denominador comum, fizemos o presente estudo

[Pathology associated with uterine leiomyoma: review of 600 cases]. / Patologia associada ao leiomioma uterino: revisão de 600 casos.

The authors analyzed 600 patients with uterine leiomyoma examined at the Escola Paulista de Medicina and submitted to surgical treatment between 1976 and 1987. The uteri were carefully studied and leiomyomas were confirmed. Other diseases were also found in 71.17% of the cases. Uteri from hysterectomies performed for conditions other than leiomyoma were also studied for control purposes. Major conditions found were chronic cervicitis; adenomyosis; follicular cysts; tubal changes (congestion, edema, and salpingitis); uterine polyps; endometrial hyperplasia; endometriosis; ovarian and endometrial neoplasias.