Diagnostic Three Slides Pap Test Compared to Punch Biopsy and Endocervical Curettage in Confirmed HSIL+ Diagnosis.

OBJECTIVE: The aim of the study was to evaluate the accuracy of the diagnostic Pap test (DPT) on three slides and punch biopsy and endocervical curettage (PB/ECC) compared with the final biopsy material in the detection of high-grade squamous intraepithelial lesion (HSIL). MATERIALS AND METHODS: Patients treated with conization after previous DPT and PB/ECC were analyzed. The findings of the DPT and PB/ECC as well as of the endocervical brush cytology and ECC were compared with the final conus histology. RESULTS: 150 patients were analyzed, and final histology verified 145 cases of HSIL and 3 cancers. The percentage of confirmed HSIL cytology was 97%, while for PB/ECC it was 79% with 30/145 false negative results. The correlation between Pap test and PB/ECC showed that the diagnostic accuracy of DPT is significantly higher (p < 0.0001). Endocervical brush cytology confirmed HSIL+ in the endocervical canal in 83% and ECC in 35% of cases (p < 0.0001). CONCLUSION: The DPT on three slides enables better detection of HSIL compared to PB/ECC, particularly for lesions localized in the endocervical canal sampled with a cytobrush. A high quality DPT could represent a surrogate for PB/ECC and open the possibility of direct access to therapeutic procedure.

The Immunohistochemical Pattern of Epithelial-Mesenchymal Transition Markers In Endometrial Carcinoma.

The majority of endometrial carcinoma are diagnosed at an early stage and exhibit a favorable prognosis. However, 10% to 15% of ECs recur and the majority are type II tumors which are high-grade carcinomas. The epithelial-mesenchymal transition (EMT) has been considered as a fundamental step for the development of the invasive phenotype of cancer cells. During EMT, many of epithelial surface markers, primarily E-cadherin disappear, and mesenchymal markers including N-cadherin gain. This feature resides predominantly at the invasive front (IF) of the tumor. Therefore, we examined the immunohistochemical expression of E-cadherin and N-cadherin at the IF, in central areas of the tumor and lymphovascular space, in type I and type II endometrial carcinoma. The association of each protein with the clinicopathologic features was also evaluated. Our results confirmed a stronger E-cadherin immunostaining in type I tumors indicating that the loss of E-cadherin may be responsible for a more aggressive behavior of type II ECs. In both types, E-cadherin was strongly expressed in central areas and the reactivity decreased toward the IF. On contrary, N-cadherin was overexpressed at the IF confirming an inverse relationship between these markers. In addition, a decrease in E-cadherin expression was observed in cells within the lymphovascular space. Downregulation of E-cadherin was associated only with high-grade tumors while no correlations between both markers and other clinicopathologic features were found. Our results confirm that EMT occurs at the IF that represents a critical interface between the tumor and the host.

Expression of CD133 and CD117 in 64 Serous Ovarian Cancer Cases.

The cancer stem cells (CSCs) represent a minority of tumor cells that are able to proliferate and self-renew and might be responsible for tumor initiation and maintenance. The CD133 and CD117 are the most commonly used markers for the putative CSCs, especially for the ovarian CSCs, but its clinical significance remains uncertain. The aim of this study was to compare the immunohistochemical expression of CD133 and CD117 in 64 primary ovarian high grade serous carcinoma and peritoneal metastasis, and to examine their potential clinical role. CD133 expression was mainly seen in the apical/endoluminal cell surface of tumor cells and was found in 61% of the carcinoma samples and 41% of the metastasis. The median of CD133 positive cells in tumors was 1 (0.1-7)%, and in metastases was 0.6 (0.1-6)%. CD117 expression appeared as a cytoplasmic and/or membranous stain and was found in 81% of the carcinoma samples and 77% of the metastasis. The median of CD117 positive cells in tumors was 1 (0.1-8)%, and in metastases was 0.1 (0.1-7)%. Multivariate analysis has shown that patients with high CD133 expression in tumor cells have significantly shorter disease free survival and overall survival (p=0.025 and p=0.014, respectively). Patients with high CD117 expression in tumor cells have significantly shorter disease free survival (p=0.031). Cox's proportional hazards model identified expression of CD133 protein in tumor as an independent prognostic factor. Our study indicates that the immunohistochemical assessment of CD133 and CD117 expression may have potential clinical value in predicting disease progression and prognosis in the high grade serous ovarian cancer. CD133 proved to be an independent prognostic factor in the high grade serous ovarian cancer patients.

Evaluation of the HPV L1 capsid protein in prognosis of mild and moderate dysplasia of the cervix uteri.

Cervical intraepithelial neoplasia (CIN) can be detected in the cytologic smears years before invasive squamous cancer arises, but no reproducible morphologic criteria exist to predict behavior of cervical lesions. The possibility of predicting the clinical course of cervical lesions could be of high value in clinical practice and some women will spare of unnecessary treatment. HPV L1 capsid protein represents about 90% of the total protein on the surface of the virus and can be detected in mild to moderate dysplasia and rarely in severe dysplasia. The purpose of the study was to evaluate the use of immunodetection of HPV L1 protein on archival Pap smears with findings of mild and moderate dysplasia in predicting its clinical course. Immunochemical analyses with L1 antibody revealed positively stained nuclei of squamous epithelial cells in 56 of 114 smears (49.1%). The staining results were correlated with follow-up smears or with histologic verification. Regression (negativisation of the Pap smear for 24 months or longer) was noticed in 31 of 56 (55.4%) L1-positive cases and in 20 of 58 (34.5%) L1-negative cases. Persistent disease occured in 13 (23.2%) L1-positive cases and in 14 (24.1%) L1-negative cases. Progressive disease occured in 12 (21.4%) L1-positive cases and in 24 (41.4%) L1-negative cases. The difference in the clinical course between the L1-positive and L1-negative patients was statistically significant (p = 0.025). Also, the difference in the clinical course of the L1-negative staining in the under-30 and over-30 years age group was statistically significant (p = 0.04). For conclusion, our data confirm that immunostaining for HPV L1 capsid protein could offer prognostic information about mild and moderate intraepithelial cervical squamous lesions.

Villoglandular papillary adenocarcinoma of the uterine cervix with aggressive clinical course--a case report.

Villoglandular papillary adenocarcinoma (VGA) of cervix is an uncommon but well recognized histologic subtype of cervical adenocarcinoma which usually affects young women. Based on the favorable outcomes reported in most previous cases the tumor is generally considered to have an indolent clinical course with excellent prognosis. We present a case of a 22-year-old woman admitted at our Department for glandular abnormality on cervical smear and episodes of vaginal discharge. In the Pap smear, the cytological features were suspicious but not diagnostic of adenocarcinoma, therefore reported as atypical glandular cells (AGC). Histological examination confirmed VGA associated with lymphovascular space invasion. The patient underwent radical operative procedure. Intraoperative cytologic examination detected pelvic lymph nodes metastasis. The patient was confirmed to be in an advanced stage - III B (FIGO). During a two years follow-up period a rapid dissemination of the tumor occurred and resulted with a fatal outcome. Although VGA has been reported to have a favorable prognosis, several cases with lymph node involvement have already been described. Cervical smears examination would be helpful for an early diagnosis of VGA, however the cytologic recognition is often difficult. Further investigation of the pathogenesis, diagnosis and therapy of the tumor is needed.

Survival of stress exposed Campylobacter jejuni in the murine macrophage J774 cell line.

Although campylobacters are relatively fragile and sensitive to environmental stresses, Campylobacter jejuni has evolved mechanisms for survival in diverse environments, both inside and outside the host. Their survival properties and pathogenic potential were assessed after subjecting food and clinical C. jejuni isolates to different stress conditions. After exposure to starvation (5 h and 15 h of nutrient depletion), a temperature shock (3 min at 55 degrees C) or oxidative stress (5 h and 15 h of atmospheric oxygen) we studied the culturability, viability and capability of adhesion, internalization and survival within the in vitro cell culture model using J774 murine macrophages. Starvation severely impaired C. jejuni culturability, particularly after 15 h of nutrient depletion. The number of viable cells decreased by 30-40%. Starved bacterial cells also showed a lower capability of adhesion, internalization and survival within macrophages. Despite the reduced culturability and viability of the heat treated cells, C. jejuni efficiently adhered to, and entered murine macrophages. However, the number of heat treated cells started to decrease more quickly than non-stressed cells. Within 24 h post infection all the cells were killed. The bacterial mechanisms involved in inactivating toxic oxygen products may enhance bacterial persistence through increased binding, entry and survival of both oxidatively stressed C. jejuni isolates inside the macrophages. Oxygen exposure increased the internalization and intracellular survival, although the cells cannot remain viable for extended periods within murine macrophages. However, any prolongation of survival in macrophages may increase the probability of transmission of bacteria in the host organism and have further implications in the pathogenesis of campylobacteriosis. This indicates that environmental stress conditions may be involved.