Wagner José Gonçalves

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.

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 ovarian cancer.

The present case-control study evaluates the role of the progesterone receptor (PR) polymorphism known as PROGINS as a risk factor for ovarian cancer development and investigates the association between these genetic variants and clinical/pathologic variables of ovarian cancer. PROGINS polymorphism was examined, by polymerase chain reaction, in a total of 80 patients with ovarian cancer and 282 control subjects. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 71.3, 15.0 and 13.8% in ovarian cancer patients and 78.37, 21.63 and 0% in controls, respectively. The chi(2)-test showed a higher incidence of the T2/T2 genotype (P=0.001) in the ovarian cancer group. In addition, women carrying a mutated allele (T2) showed approximately 2.2 times higher risk of ovarian cancer development as compared to women who have a variant allele (odds ratio (OR)=2.2; 95% CI=1.80-3.54). Regarding the clinical and pathologic findings observed within the cancer group, there was a significant correlation between PROGINS polymorphism and patients with a familial history (chi(2)=6.776; P=0.009; Fischer exact test, P=0.01). In this regard, patients with familial antecedents have a 4.7 times higher likelihood to have at least one risk allele (T2) as compared with patients without familial antecedents (OR=4.69; 95% CI=1.38-15.87). 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 ovarian cancer.

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 χ2 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.

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.

Effects of simple hysterectomy on bone loss

Lumbar spine and proximal femoral bone densities of Caucasian women, aged 35-45, were measured by dual photon densitometry model DPX. The measurement sites were assessed at the lumbar spine (vertebrae L2 to L4) and at the proximal femur (trochanter, femoral neck and Wards triangle). After exclusion of women with climacteric symptoms, sterilized patients or those with menopausal concentrations of gonadotrophins, the study included 22 subjects: 11 menstruant (control group) and 11 hysterectomized. The hysterectomies were without oophorectomy and had been performed during the previous five years. The bone densities of the hysterectomized women were lower than those of the normal ones, but significantly lower at the Wards triangle.

Cox-2, EGFR, and ERBB-2 expression in cervical intraepithelial neoplasia and cervical cancer using an automated imaging system.

We hypothesized that the activation of cyclooxygenase (COX)-2, epidermal growth factor receptor (EGFR), and ErbB-2 signaling is required for cervical intraepithelial neoplasia (CIN) lesions to progress to cervical cancer. A retrospective analysis was performed in 179 patients with Stage I squamous cell carcinoma (SCC) and 233 patients with CIN (112 CIN I, 47 CIN II, and 74 CIN III). COX-2, EGFR, and ErbB-2 expression was analyzed by immunohistochemistry using the ACIS III automated imaging system. The mean expression of COX-2, EGFR, and ErbB-2 was compared between the various stages of CIN and SCC. COX-2 mean expression was predominantly cytoplasmic, increasing significantly from CIN I to CIN II, CIN III, and SCC (P<0.001). EGFR mean expression also rose significantly during tumor progression from CIN I to SCC (P=0.001). CIN I samples were negative for ErbB-2 expression. CIN II, CIN III, and SCC were considered positive for ErbB-2 expression in 2.2%, 14%, and 16.2% of cases, respectively. There was also a statistically significant correlation between increase of ErbB-2 positivity from CIN to SCC. We conclude that COX-2, EGFR, and ErbB-2 expression increase significantly during the progression of CIN to cancer.

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 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.

Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil.

CONTEXT AND OBJECTIVE The Wnt pathway is involved in tumorigenesis of several tissues. For this reason, we proposed to evaluate Wnt gene expression in endometrial cancer type I. DESIGN AND SETTING Cross-sectional study on materials gathered from the tissue bank of the Department of Pathology, Universidade Federal de São Paulo. METHODS Endometrial specimens were obtained from surgeries performed between 1995 and 2005 at São Paulo Hospital, Universidade Federal de São Paulo. The material was divided into two groups according to tissue type: Group A, atrophic endometrium (n = 15); and Group B, endometrial adenocarcinoma (n = 45). We compared the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) and beta-catenin between endometrial cancer type I and atrophic endometrium. RESULTS Regarding Wnt1, FZD1 and Wnt5a expression, no significant association was observed between the groups. A significant association was observed between the groups in relation to FZD5 expression (P = 0.001). The proportion of FZD5-positive samples was significantly higher in group A (80.0%) than in group B (31.1%). Regarding the survival curve for FZD5 in group B, we did not find any significant association between atrophic endometrium and endometrial adenocarcinoma. We also did not find any significant association regarding beta-catenin expression (P = 1.000). CONCLUSION FZD5 is downregulated in endometrial adenocarcinoma, in comparison with atrophic endometrium.