Association between Toll-like receptor and tumor necrosis factor immunological pathways in uterine cervical neoplasms.

INTRODUCTION: The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inflammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions. METHODS: A total of 64 embedded tissues were obtained from gynecological procedures, including 35 specimens with cervical intraepithelial neoplasia (CIN) and 10 specimens with cervical squamous cell carcinoma (CSCC) as well as 19 normal cervical samples. The expression of TLR2, TLR3, TLR4, TNF-α and TNF-ß was measured by immunohistochemistry and graded into low and high levels of expression. RESULTS: There was an association between the expression levels of TLR2 and those of TNF-α and TNF-ß (p = 0.01 and p = 0.021, respectively) in the cervical cancer and CIN groups. TLR4 expression was associated with TNF-α and TNF-ß expression (p = 0.016 and p = 0.025, respectively) in these 2 groups. By contrast, TLR3 was not statistically associated with TNF-α or TNF-ß in any of the groups. CONCLUSIONS: There might be an association of the TLR2 and TLR4 pathways with the immunological response of TNF-α and TNF-ß in cervical cancer. These markers are also expressed at higher levels in cervical cancer and premalignant lesions compared to normal controls.

Comparative study of different histologic classifications in the degree of differentiation in endometrial adenocarcinoma.

PURPOSE: To evaluate the concordance among the available histologic classifications for endometrial adenocarcinoma using interobserver and intraobserver agreement as well as the association of tumor histologic degree in the above mentioned classifications with cellular proliferation measured by Ki-67. METHODS: Seventy women who underwent surgical treatment of endometrial adenocarcinoma with histologic confirmation of endometrioid type were included in the study. Two experienced pathologists randomly analyzed the slides in 3 distinct timeframes with a maximum of 25 slides/timeframe. Tumor slides were classified according to the degree of differentiation using 4 different classifications: International Federation of Gynecology and Obstetrics (FIGO), modified FIGO, Lax, and Alkushi. RESULTS: Intraobserver agreement was reasonable for classification of FIGO (k 0.469 and 0.538), very good for modified FIGO (k 0.661 and 0.768), moderate for Lax classification (k 0.496 and 0.466), and moderate/good for Alkushi classification (k 0.528 and 0.736). Interobserver concordance was regular for FIGO classification (k = 0.271 and 0.343), good/moderate for modified FIGO classification (k = 0.661 and 0.522, respectively), regular/moderate for Lax classification (k = 0.258 and 0.465, respectively), and regular for Alkushi classification (k = 0.283 and 0.402). CONCLUSIONS: The prognostic value of histologic grading in endometrial carcinoma and its importance for a successful therapeutic plan have been documented repeatedly, but the best grading system, in terms of prognostication, reproducibility, ease of use, and universality (e.g., applicability to all tumor cell types), has not been unequivocally defined.

Evaluation of N-acetilglucosaminidase and myeloperoxidase activity in patients with endometriosis-related infertility undergoing intracytoplasmic sperm injection.

AIM: Inflammation is as an important factor in ovulation with the active participation of leucocytes and their inflammatory mediators. The present study was performed to compare the activity of the inflammatory enzymes myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in patients with endometriosis-related infertility and in normally ovulating women undergoing intracytoplasmic sperm injection (ICSI). MATERIAL AND METHODS: This prospective study included infertile women undergoing ICSI treatment. These women were divided into two groups: endometriosis anovulation (n = 18) and normally ovulating (n = 20). NAG and MPO activity was evaluated colorimetrically in serum and in follicular fluids obtained at the time of oocyte retrieval. RESULTS: There was a significant correlation between the serum and follicular fluid activities of NAG and MPO (τ = 0.256, P = 0.025; and τ = -0.234, P = 0.041; respectively). Both serum and follicular fluid NAG activities were higher in patients with endometriosis compared to the control group (P < 0.001). MPO follicular fluid activity was lower in patients with endometriosis compared to normally ovulating women (P = 0.016). CONCLUSION: Infertile patients with endometriosis show a distinct pattern of serum and follicular fluid macrophage/neutrophil activation compared to normally ovulating women undergoing ICSI, which may reflect the role of immune and inflammatory alterations in endometriosis-related infertility.

Expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen.

This study was undertaken to investigate the expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen (TAM). Postmenopausal women with endometrial polyps treated with TAM (n = 20), postmenopausal women with endometrial polyps without hormone use (n = 20), postmenopausal women with atrophic endometrium (n = 20), and postmenopausal women with endometrial adenocarcinoma (n = 20) were prospectively investigated. Tissue samples were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. The data were analyzed using the Student t test, analysis of variance, and χ2 to evaluate significant differences between the groups. The level of significance was set at P < 0.05. There was no difference in the expression of p53 between the groups (P = 0.067). The expression of Ki-67 was higher in the polyp samples from TAM-treated women compared with those from the women using no hormone (P = 0.0047) and those from the women with atrophic endometrium (P = 0.008). Samples from the women with endometrial cancer was associated with higher Ki-67 expression compared with the polyp samples from TAM-treated women (P = 0.004). The expression of CD31 was higher in the polyp samples of TAM-treated women compared with that of the samples from the women with atrophic endometrium (P < 0.001) and similar to the polyp samples from the women using no hormone (P = 0.319) and to the samples from the women with endometrial cancer (P = 0.418). The use of TAM in postmenopausal women might be associated with increased cellular proliferation in endometrial polyps without interfering angiogenesis or inactivation of tumor suppressor proteins.

Histopathological and immunohistochemical (cytokeratins AE1/AE3) study of the parametrium of patients with early stage cervical cancer.

OBJECTIVE: This study was undertaken in order to evaluate histopathological and immunohistochemical (cytokeratins AE1/AE3) characteristics of parametrial invasion in patients with early stage cervical cancer. STUDY DESIGN: Thirty patients with stage IB squamous cell carcinoma (SCC) of the cervix submitted to radical hysterectomy from November 2001 to September 2002 were prospectively studied. Histopathological studies were undertaken using tissue samples (n=60) taken from the parametrium, whose surgical margins were inked and the entire parametrial tissue was fixed in 10% buffered formalin and embedded in paraffin for further analysis using hematoxylin-eosin (H&E) staining. Specific patterns of parametrial involvement (continuous invasion, parametrial lymphatic vascular space invasion (LVSI) and/or parametrial lymph nodes' (PMLN) metastasis) were recorded. Parametrial samples, in which the histological examination showed no tumor involvement, were immunohistochemically assessed through monoclonal antibodies for cytokeratins AE1/AE3. Clinicopathological characteristics of the patients were also recorded. RESULTS: Patient's mean age was 49+/-10 years (27-73 years). Histopathological analysis (H&E) showed parametrium involvement in 12 patients (40%) of whom 11 (92%) presented parametrial LVSI, 9 (75%) continuous invasion and 4 (33%) PMLN metastasis. Micrometastasis was detected in 3/18 (17%) of the patients with histologically negative parametrium by H&E evaluation. Parametrial involvement detected by H&E was associated with tumor recurrence (p=0.009) and survival (p=0.025). This association was not correlated with the presence of parametrial micrometastasis (p=1.00 and 1.00, respectively). CONCLUSIONS: The process of parametrial spreading in patients with SCC of the cervix may develop several histopathological patterns, which are associated with clinicopathological features and prognosis. Our findings highlight the importance to ink the parametria, which is the only way to define the pattern of tumor spreading. The clinical significance of micrometastasis, detected in patients with histologically negative parametrium by H&E, remains to be clear.

Comparative study of autologous pubovaginal sling and synthetic transobturator (TOT) SAFYRE sling in the treatment of stress urinary incontinence.

PURPOSE: To compare short-term results of autologous pubovaginal sling and synthetic transobturator (TOT) SAFYRE sling in the treatment of female stress urinary incontinence (SUI). METHODS: Twenty women referred for surgical treatment of SUI were assigned randomly to autologous pubovaginal sling or synthetic TOT sling. Inclusion criteria were primary treatment of SUI and urodynamic study showing SUI without detrusor overactivity. Pre- and postoperative quantification of the severity of incontinence was done by pad test and a validated questionnaire (King's Health Questionnaire). RESULTS: There were no differences in patients' mean age, parity, body mass index, rate of postmenopausal state, pelvic floor defects and mean Valsalva leak point pressure in the preoperative urodynamic study. Mean operating time (21.1 +/- 3.8 vs. 69.5 +/- 23.7 min; P < 0.001) and hospital stay (28.8 +/- 8.4 vs. 44.4 +/- 5.8 h; P < 0.001) was shorter in the TOT than the autologous group. The postoperative pad test (39.4 +/- 12.5 vs. 8.4 +/- 5.2 g; P = 0.01) and the absent in the improvement in the quality of life were significantly higher in the TOT group. CONCLUSION: Our initial results suggest that the synthetic TOT technique had worse effectiveness for treating female SUI compared to autologous pubovaginal sling.

Prolapso de tuba uterina após histerectomia vaginal: relato de caso / Fallopian tube prolapse after vaginal hysterectomy: a case report

O prolapso de tuba uterina é complicação rara após histerectomia, com aproximadamente 80 casos descritos na literatura. A sintomatologia é inespecífica, podendo incluir sangramento genital, dispareunia e dor pélvica crônica. O diagnóstico diferencial deve ser feito com granuloma de cúpula vaginal e carcinoma de vagina. O tratamento deve ser individualizado, podendo ser realizado por via vaginal, abdominal ou laparoscópica. Relatamos o caso de uma paciente, 47 anos, com miomatose uterina, submetida a histerectomia vaginal, evoluindo com prolapso de tuba uterina após 11 meses de pós-operatório. O exame especular evidenciava lesão vegetante, friável e sangrante localizada na cúpula vaginal. Esses achados clínicos sugeriam o diagnóstico de prolapso de tuba uterina. A paciente foi submetida a nova intervenção cirúrgica, com ressecção da tuba uterina por via vaginal. O exame natomopatológico confirmou o diagnóstico e a paciente evoluiu com remissão completa da sintomatologia.