Malignant mesothelioma of the peritoneum mimicking primary peritonitis carcinomatosis.

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Validation of Revised FIGO Staging Classification for Cancer of the Ovary, Fallopian Tube, and Peritoneum Based on a Single Histological Type.

OBJECTIVE: This study aimed to evaluate the prognostic significance of revised International Federation of Gynecology and Obstetrics (FIGO2013) staging classification for cancer of the ovary, fallopian tube, and peritoneum in patients exhibiting high-grade serous histology. METHODS: Clinical records of patients with high-grade serous carcinoma who underwent primary surgery between 2007 and 2012 were reviewed retrospectively. Patients were reclassified according to the FIGO2013 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated for each stage using Kaplan-Meier estimates and compared with the log-rank test. RESULTS: In total, 125 patients were included in the analysis. The distribution of the study cohort according to the revised classification was as follows; stage I, 6 patients; stage II, 9 patients; stage III, 85 patients; and stage IV, 25 patients. Median follow-up time was 36 months (95% confidence interval [CI], 3-110). The median PFS and OS were 14 months (95% CI, 12.4-15.6) and 60 months (95% CI, 47.0-72.9), respectively. Both PFS and OS were significantly different among stages I, II, III, and IV (P < 0.01). Subgroup analyses for stage III disease also revealed significant differences in survival. The median PFS for stages IIIA1, IIIB, and IIIC was 56, 46, and 16 months, respectively (P < 0.01), and the median OS was 104, 95, and 60 months, respectively (P = 0.03). The outcomes of patients with stage IV disease differed slightly but nonsignificantly according to new substages. The median PFS for stages IVA and IVB was 12 and 6 months, respectively (hazard ratio, 1.16; 95% CI, 0.48-2.79; P = 0.72), and the median OS was 41 and 24 months, respectively (hazard ratio, 1.62; 95% CI, 0.58-4.55; P = 0.35). The study sample was insufficient in size for subgroup analyses in stages I and II. CONCLUSIONS: The revised FIGO2013 staging system is highly prognostic for discriminating outcomes of patients with high-grade serous carcinoma across stages I to IV, in subgroups of stage III, but not in subgroups of stage IV.

Analysis of Metastatic Regional Lymph Node Locations and Predictors of Para-aortic Lymph Node Involvement in Endometrial Cancer Patients at Risk for Lymphatic Dissemination.

OBJECTIVE: The aim of this study was to provide detailed knowledge of the metastatic lymph node (LN) locations and to determine factors predicting para-aortic LN metastasis in endometrial cancer patients at risk (intermediate/high) for LN involvement. METHODS: A prospective case series with planned data collection was conducted in a total of 173 patients who treated with systematic pelvic para-aortic lymphadenectomy up to the renal vessels. All the LNs removed from pelvic and para-aortic basins­low or high according to the level of the inferior mesenteric artery­were evaluated separately. Logistic regression analyses were performed to determine the impact of variables on para-aortic metastasis. RESULTS: Lymph node metastasis was observed in 21.9% of the patients, pelvic LN involvement in 17.9%, para-aortic LN involvement in 15.0%, both pelvic and para-aortic LN involvement in 10.9%, and isolated para-aortic LN involvement in 4.0%. The most common metastatic LN locations were the external iliac (50.0%), obturator (50.0%), and low precaval regions (36.8%). The least common location of metastasis was the high precaval region (5.3%). Among patients with para-aortic LN metastasis, 42.3% had metastasis above the inferior mesenteric artery. The number of metastatic pelvic LNs greater than or equal to 2 was the only independent predictor of para-aortic metastasis in multivariate analysis (odds ratio, 23.38; 95% confidence interval, 1.35-403.99; P = 0.030), with 96.94% sensitivity, 95.87% specificity, 98.6% positive predictive value, and 97.0% negative predictive value. CONCLUSIONS: The current study supports the idea that in patients at risk of LN involvement, the systematic lymphadenectomy should be performed up to the renal vessels due to the high rate of upper level involvement.

Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists.

Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.

Breast involvement in visceral leishmaniasis.

Visceral leishmaniasis usually involves the bone marrow, lymph nodes, liver and spleen. Involvement of the eye or respiratory or gastrointestinal systems is very rare and usually occurs in immunodepressed patients. Only one case of breast involvement by protozoa has been reported in the literature. We report a case of a visceral leishmaniasis with a solid breast mass caused by leishmania and diagnosed by sonography-guided core biopsy.

Stanniocalcin-2 May Be a Potentially Valuable Prognostic Marker in Endometrial Cancer: a Preliminary Study.

In the current study, we primarily aimed to investigate stanniocalcin-2 (STC2) protein expression pattern in hysterectomy specimens from patients with endometrioid type endometrial cancer (EC) using immunohistochemistry. Secondly, in order to clarify its prognostic impact, we examined relationships of the expression levels of STC2 with clinicopathologic features and outcome of patients. Histopathology slides of 49 patients were stained with the monoclonal mouse antibody targeting STC2 protein. The expression levels of STC2 were classified based on three-tiered semiquantitative scheme: negative expression, expression level of 0; low-expression, expression level of 1+; and high-expression, expression levels of 2+ and 3+. Recurrence-free survival (RFS) was used as the primary prognostic outcome. Immunohistochemical analysis revealed that 73.5% of tissue samples exhibited positive staining with STC2. The intensity of staining with STC2 was weak in 40.8%, moderate in 22.4%, and strong in 10.2%. Thirty-eight percent of samples showed negative expression; 18.4%, low-expression (1+); and 42.8%, high-expression (2 to 3+). High-expression of STC2 was significantly associated with grade 2-3 tumors (p = 0.026) and disease recurrence (p = 0.013). Multivariate analysis revealed that both the tumor grade and STC2 were independent predictors of disease recurrence. Kaplan-Meier analyses confirmed that patients with high-expression of STC2 had a significantly poorer RFS than those with negative or low STC2 expression (p = 0.037); although overall survival did not differ with respect to expression levels of STC2 (p = 0.148). In conclusion, high-expression of STC2 is a negative prognostic factor, associated with increased risk of recurrence in endometrioid EC.

Neoangiogenesis and expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor, and glucose transporter-1 in endometrioid type endometrium adenocarcinomas.

OBJECTIVE: Hypoxia Inducible Factor-1alpha (HIF-1alpha) is a transcriptional factor that activates multiple genes including Vascular Endothelial Growth Factor (VEGF) and glucose transporter-1 (GLUT-1) in response to hypoxia and promotes neoangiogenesis. METHODS: Expression of HIF-1alpha VEGF, and GLUT-1 were analyzed by immunohistochemistry and microvessel density (MVD) was determined by CD 34 immunostaining in 100 endometrioid type endometrial adenocarcinoma, FIGO Stages I-IV. RESULTS: High expression of HIF-1alpha, VEGF and GLUT-1 were significantly more prevalent in advanced stages than early stages (p<0.001). High expression of HIF-1alpha was found in 100% of Stage III-IV patients, whereas 50% of Stage II and 9% of Stage I patients had high HIF-1alpha expression. Similarly, high VEGF expression was determined in 4% of Stage I and 30% of Stage II patients, however 90% of Stage III-IV patients had high expression of VEGF. Comparing the GLUT-1 scores, it was found that increasing stages correlated with high GLUT-1 expression. Additionally, a statistically significant difference was also noted in MVD between stages (p<0.001). The average MVD of Stage I patients was 31.87+/-7.73. It was found 49.24+/-7.60 in Stage II, and 78.74+/-14.48 in Stage III-IV patients. On analyzing expression of HIF-1alpha, VEGF and GLUT-1 and MVD in pairs, statistically significant correlations were found between each other (p<0.001). CONCLUSION: HIF-1alpha was increasingly expressed from early stages through advance stages of endometrioid adenocarcinoma, paralleled by activation of its downstream genes such as GLUT-1, VEGF and increased angiogenesis. These results highlight the importance of hypoxia and related pathways in progression of endometrial carcinoma.

Relationships of nuclear, architectural and International Federation of Gynecology and Obstetrics grading systems in endometrial cancer.

OBJECTIVE: To examine correlations among nuclear, architectural, and International Federation of Gynecology and Obstetrics (FIGO) grading systems, and their relationships with lymph node (LN) involvement in endometrioid endometrial cancer. MATERIAL AND METHODS: Histopathology slides of 135 consecutive patients were reviewed with respect to tumor grade and LN metastasis. Notable nuclear atypia was defined as grade 3 nuclei. FIGO grade was established by raising the architectural grade (AG) by one grade when the tumor was composed of cells with nuclear grade (NG) 3. Correlations between the grading systems were analyzed using Spearman's rank correlation coefficients, and relationships of grading systems with LN involvement were assessed using logistic regression analysis. RESULTS: Correlation analysis revealed a significant and strongly positive relationship between FIGO and architectural grading systems (r=0.885, p=0.001); however, correlations of nuclear grading with the architectural (r=0.535, p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN involvement rates differed significantly between tumors with AG 1 and those with AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast, although the difference in LN involvement rates failed to reach statistical significance between tumors with NG 1 and those with NG 2, it was significant between NG 2 and NG 3 (p=0.042). Although all three grading systems were associated with LN involvement in univariate analyses, an independent relationship could not be established after adjustment for other confounders in multivariate analysis. CONCLUSION: Nuclear grading is significantly correlated with neither architectural nor FIGO grading systems. The differences in LN involvement rates in the nuclear grading system reach significance only in the setting of tumor cells with NG 3; however, none of the grading systems was an independent predictor of LN involvement.

Impact of coexistent adenomyosis on outcomes of patients with endometrioid endometrial cancer: a propensity score-matched analysis.

PURPOSE: Despite the common occurrence of adenomyosis in endometrial cancer (EC), there is a paucity and conflict in the literature regarding its impact on outcomes of patients. We sought to compare outcomes of patients with endometrioid type EC with or without adenomyosis. METHODS: A total of 314 patients were included in the analysis. Patients were divided into 2 groups according to the presence or absence of adenomyosis. Adenomyosis was identified in 79 patients (25.1%). A propensity score-matched comparison (1:1) was carried out to minimize selection biases. The propensity score was developed through multivariable logistic regression model including age, stage, and tumor grade as covariates. After performing propensity score matching, 70 patients from each group were successfully matched. Primary outcome of the study was disease-free survival (DFS), and the secondary outcomes were overall survival (OS) and disease-specific survival (DSS). RESULTS: Median follow-up time was 61 months for the adenomyosis positive group and 76 months for the adenomyosis negative group. There were no statistically significant differences in 3- and 5-year DFS, OS, and DSS rates between the 2 groups. Five-year DFS was 92% vs 88% (hazard ratio [HR] 1.54 [0.56-4.27]; p = 0.404), 5-year OS was 94% vs 92% (HR 1.60 [0.49-5.26]; p = 0.441), and 5-year DSS was 94% vs 96% (HR 2.51 [0.46-13.71]; p = 0.290) for patients with and without adenomyosis, respectively. CONCLUSIONS: Coexistent adenomyosis in EC is not a prognostic factor and does not impact survival outcomes.

The clinical impact of serous tubal intraepithelial carcinoma on outcomes of patients with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum.

AIMS: To investigate whether the presence of serous tubal intraepithelial carcinoma (STIC) is associated with clinical outcomes in a nonselected (unknown BRCA status) cohort of patients with a high-grade serous carcinoma (HGSC) of the ovary, fallopian tube, and peritoneum. SETTINGS AND DESIGN: A prospective case-series with planned data collection. SUBJECTS AND METHODS: The study was conducted in a total of 131 patients, who underwent primary cytoreductive surgery between 2007 and 2012. Histological examination of the fallopian tubes included the "sectioning and extensively examining the fimbriated end" protocol. The diagnosis of STIC was based on the combination of morphology and immunohistochemistry. The patients were divided into two groups according to the absence or presence of STIC and compared clinicopathologically. STATISTICAL ANALYSIS USED: Analyses were performed using PASW 18 (SPSS/IBM, Chicago, IL, USA) software. The primary outcome was progression-free survival (PFS), and the secondary outcome was overall survival (OS). RESULTS: STIC was identified in 20.6% of patients. Median follow-up time was 49.5 months for the STIC-positive group and 38.0 months for the STIC-negative group. Study groups were comparable in terms of clinicopathological characteristics with the exception that patients with STIC had less lymph node involvement (55.0% vs. 65.4%, P = 0.001), and more diagnosis of primary tubal carcinoma (29.6% vs. 3.8%, P = 0.001) compared to those without STIC. No statistically significant differences in terms of PFS (P = 0.462) and OS (P = 0.501) were observed between the groups. CONCLUSIONS: The absolute identification of the origin of tumor cell does not seem to significantly affect the clinical course of the patients with HGSC.

A study detection of the ROS1 gene fusion by FISH and ROS1 protein expression by IHC methods in patients with ovarian malignant or borderline serous tumors.

OBJECTIVE: ROS1 is an orphan receptor protein tyrosine kinase which is supposed to undergo genetic rearrangement in carcinogenesis. In the current study, we aimed to investigate the frequency and clinicopathologic features associated with ROS1 gene fusion and ROS1 protein expression in patients with ovarian serous carcinoma or serous borderline tumors. MATERIALS AND METHODS: Tissue samples of 102 patients with high or low grade serous carcinoma and borderline serous tumors were selected randomly from the archives of Department of Gyneco-pathology, and analyzed for ROS1 gene expression. (Fluorescence in situ hybridization (FISH) method was used to assess ROS1 gene rearrangement, while ROS1 protein expression was analyzed using immunohistochemistry. RESULTS: The study consisted of 94 cases of high-grade serous carcinoma (92.1%), 2 cases of low-grade serous carcinoma (%2) and 6 cases of serous borderline tumor (5.9%). ROS1 gene rearrangement analysis revealed that 4 patients (3.9%) were FISH-positive; whereas the immunohistochemical analysis yielded only 1 patient (0.9%) exhibiting faint positive expression of ROS1 protein. Given the low incidences of ROS1 gene rearrangement and protein expression, their relationships with clinicopathologic parameters could not be statistically analyzed. CONCLUSION: Although rare, patients with ovarian serous carcinoma or serous borderline tumor may exhibit ROS1 gene rearrangement and ROS1 protein expression. Further large-scale studies are necessary to explore the clinicopathologic significance of ROS1 gene expression in ovarian serous carcinoma.

TRAIL death receptor-4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

PURPOSE: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. METHODS AND MATERIALS: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. RESULTS: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. CONCLUSIONS: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis.

OBJECTIVE: Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. MATERIAL AND METHOD: 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. RESULTS: We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". CONCLUSION: In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

In situ hybridization analysis of invasive breast carcinomas with immunohistochemically negative Her-2 status (a national multicenter study).

OBJECTIVE: The aim of this study was to determine the rate of Her-2 gene amplification in breast cancer cases with a previous negative Her-2 result as determined by immunohistochemistry (score 0 or 1). MATERIAL AND METHOD: 552 cases of invasive breast carcinoma were assessed with the contribution of 9 centers. Previous immunohistochemistry score was either 0 or 1+ in all cases. These cases were re-tested by Her-2 silver in situ hybridization in the central laboratory. Her-2 gene amplification was defined as Her-2/CEP 17 ratio of more than 2.2. Cases with a ratio between 1.8 and 2.0 were defined as equivocal and cases with a ratio of less than 1.8 were defined as negative. RESULTS: Re-testing of the 552 cases with silver in situ hybridization showed a total of 22 cases with Her-2 gene amplification, of which 11 (3.2%) were found to be score 0, and 11 were found to be score 1+ (5.3%) by immunohistochemistry previously. Her-2 gene amplification rate of cases (score 0 and 1+) ranged from 0% to 10.48% among the centers. Polysomy was found in 28 (8.1%) of the score 0 cases and 25 (12.1%) among the score 1+ cases. Five (9.4%) of the cases with polysomy were found to be amplified, and 48 (90.6%) were not. CONCLUSION: The results of the study show that a group of cases (3.98%) with a potential to benefit from anti-Her-2 therapy may be missed with the immunohistochemical method. This indicates the importance of quality assurance, especially in central laboratories with many breast cancer cases in daily practice.

Elastic light single-scattering spectroscopy for the detection of cervical precancerous ex vivo.

Potential application of elastic light single-scattering spectroscopy (ELSSS) for differentiating high-grade squamous intraepithelial lesions (HSIL) from non-HSIL tissues was investigated. An ELSSS system was used to acquire spectra from cervix tissues. A single-fiber optical probe with a diameter of 100 µm was used for both delivery and detection of white light to and from the cervix tissue. Spectroscopic measurements were acquired from 95 ex vivo biopsy samples of 60 pap smear positive patients and normal cervix tissue from 10 patients after hysterectomy were used as a negative control group. Spectroscopic results of 95 cervix biopsy were compared to the histopathology of the biopsy samples. Sensitivity and specificity of the ELSSS system in the differentiation of HSIL and non-HSIL tissues are 87.5% and 45.6%, respectively, for the pap smear and colposcopy positive biopsy samples. The ELSSS system has the potential for use in real-time diagnosis of HSIL tissues as an adjunct to Papanicolaou test (pap smear) and colposcopy.

Preliminary results of the first human uterus transplantation from a multiorgan donor.

OBJECTIVE: To describe the first-year results of the first human uterus transplantation case from a multiorgan donor. DESIGN: Case study. SETTING: University hospital. PATIENT(S): A 21-year-old woman with complete müllerian agenesis who had been previously operated on for vaginal reconstruction. INTERVENTION(S): Uterus transplantation procedure consisting of orthotopic replacement and fixation of the retrieved uterus, revascularization, end to site anastomoses of bilateral hypogastric arteries and veins to bilateral external iliac arteries and veins was performed. MAIN OUTCOME MEASURE(S): Resumption of menstrual cycles. RESULT(S): The patient had menarche 20 days after transplant surgery. She has had 12 menstrual cycles since the operation. CONCLUSION(S): We have described the longest-lived transplanted human uterus to date with acquirement of menstrual cycles.

Heterotopic triplet pregnancy (twin tubal) in a natural cycle with tubal rupture: case report and review of the literature.

The incidence of heterotopic/ectopic pregnancy has risen in recent years, largely due to more frequent use of ovulatory medicine and increased incidence of pelvic inflammatory disease. In a natural cycle, it is a very rare event. Most heterotopic/ectopic pregnancies are localized in the uterine tube and, usually, it is diagnosed when symptoms develop. We report the case of a 37 year-old, gravida 2, para 0, abortion 1 woman with no known risk factors for heterotopic pregnancy. The patient attended the emergency department because of acute abdominal pain. She was evaluated in our department and a heterotopic twin pregnancy in the tube was diagnosed by transvaginal sonography. Intrauterine pregnancy with positive fetal cardiac activity at 9 weeks of gestation according to crown-rump length measurement was detected. Laparotomy was carried out because of acute abdominal syndrome. Right ruptured tubal ectopic/heterotopic pregnancy and hemoperitoneum were diagnosed. Right salpingectomy was carried out. Pathology revealed monochorionic twin tubal pregnancy. In a review of the literature, this is first case of twin tubal pregnancy in one uterine tube. In conclusion, heterotopic pregnancy in twin form in the uterine tube is possible in natural cycles. Intrauterine pregnancy does not exclude extrauterine pregnancy in natural cycles.

Small cell carcinoma of the cervix: a case report.

Small cell carcinoma of the uterine cervix accounts for 1-3% of all cervix cancers. It is an aggressive disease with a poor prognosis. To date, no effective treatment protocol has been determined. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. Recent data suggests that survival in patients with early staged small cell carcinoma of the cervix is better with surgery combined with chemo-radiotherapy. Here, we presented two patients with stage IB1 small cell carcinoma of the uterine cervix. For both patients, definitive surgery was performed with pelvic and para-aortic lymphadenectomy. Subsequently, they were treated with pelvic external radiotherapy and high-dose-rate intracavitary brachytherapy with concurrent cisplatin based chemotherapy. They were alive with no evidence of disease at 91 and 65 months, respectively.

PTEN-mediated Akt activation in human neocortex during prenatal development.

Akt is a crucial factor for cell survival and migration. Phosphatase and tensin (PTEN) negatively regulates cell growth and survival by inhibiting PI3K-dependent signaling. PTEN also blocks Akt phosphorylation, a main downstream molecule of PI3K cascade. So far, no studies have shown PTEN expression and Akt phosphorylation levels in the developing human neocortex. Our hypothesis is that spatial and temporal expression of PTEN is likely to modulate developing human brain cortical modeling by regulating Akt activation. Therefore, our aim is to analyze the expression pattern of PTEN and phospho-Akt levels using immunohistochemistry, Western blot, and semiquantitative analysis in the developing human neocortex (n=13 fetuses from first, second, and third trimesters). PTEN expression was decreased parallel to development, but some cells revealed strong nuclear immunoreactivity in the developing neocortex while the active Akt level was increased. Double immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA)-Tuj1 (as neuronal marker) and PCNA-GFAP (Glial marker) to the subsequent sections of PTEN and Akt-stained slides. PCNA (+) cells were mostly positive for glial fibrillary acidic protein (GFAP) and correlated with active-Akt immunoreactivity. Our results suggest that Akt-mediated signaling plays an active role in cell migration, survival, and cerebral cortical modeling throughout prenatal life and that PTEN is the most likely protein to regulate this signaling.

Clinical importance of circulating and cellular expression levels of Fas and Fas ligand in pediatric patients with lymphoproliferative malignancies.

Objectives of this study were to determine the extend of soluble Fas (sFas) and soluble FasL (sFasL) at the time of diagnosis and to evaluate its prognostic relevance under chemotherapy in childhood lymphoproliferative malignancies. The authors measured the circulating sFas and sFasL by ELISA in 25 children with newly diagnosed either ALL or NHL, as well as their expression of Fas and FasL at the time of diagnosis and remission. They did not observe any statistically significant difference between the patient group and age-matched healthy controls for sFas levels, whereas sFasL concentration in study population at the time of diagnosis was significantly higher than that in control subjects (1.05 +/- 1.46 vs. 0.36 +/- 0.18 ng/mL, p = .024). At remission the authors observed a significant decrease in the sFasL levels of all patients whose sFasL concentrations were above the minimal detectable level at the time of diagnosis (p = .008). sFasL and Fas/FasL immunohistochemical staining did not have an effect on survival. sFasL may be a marker in monitoring complete remission in children with LPM.