Seyda Karaveli

Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries

Recently, considerable attention has been focused on the role of the small heat‐shock protein group hsp27, hsp70 and hsp90 in the clinical outcome of several malignancies. However, conflicting data exist regarding the prognostic role of hsp27 expression in ovarian carcinoma, and the prognostic significance of hsp70 and hsp90 expression still remains unknown in these tumours. The purpose of this study was to investigate immunohistochemically whether hsp27, hsp70 and hsp90 expression was associated with clinicopathological parameters and survival in 52 epithelial ovarian carcinomas. Chi‐square test, Kaplan‐Meier and Cox regression analysis were used for statistical analysis. Among clinicopathological parameters, hsp27, hsp70 and hsp90 expression was only correlated with FIGO stage; hsp70 and hsp90 positivity failed to detect survival. However, the overall survival rate of patients with hsp27 expression was 13%, which was significantly worse than that of patients without hsp27 expression (47%) (p<0.01). The prognosis was also adversely affected by FIGO stage (p<0.01) and presence of ascites (p<0.01). In multivariate analysis, hsp27 expression and FIGO stage were independent prognostic variables. Our results indicate that hsp70 and hsp90 expression had no prognostic relevance in epithelial ovarian carcinomas. However, hsp27 expression and FIGO stage in these tumours could be reliable indicators of prognosis.

Neoangiogenesis and expression of hypoxia-inducible factor 1α, 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.

C‐kit protein expression in uterine and ovarian mesenchymal tumours

The protooncogene c‐kit encoding transmembrane tyrosine kinase receptor protein plays an important role in the signal transduction pathway that regulates cellular growth and repair. Gene product KIT overexpression has been shown in a number of different neoplasms, particularly in mastocytosis and gastrointestinal stromal tumours (GIST). The morphologic similarity of uterine mesenchymal tumours and GIST, and the presence of KIT protein in normal uterine tissue, suggests that uterine sarcomas may have the same c‐kit overexpression. The purpose of this study was to determine the overexpression of c‐kit protein in uterine and ovarian sarcomas. Immunohistochemical staining using a polyclonal anti‐c‐kit antibody was performed on tissue blocks from 12 carsinosarcomas, 14 leiomyosarcomas, 8 endometrial stromal sarcomas, 2 adenosarcomas, 1 atypical leiomyoma, 1 leiomyoma with limited experience, and 10 leiomyomas. The slides were evaluated by a semiquantitative method. C‐kit was positive in 10 of 12 (83%) carcinosarcomas, 10 of 14 (71%) leiomyosarcomas, 6 of 8 75(%) endometrial stromal sarcomas, 1 of 2 (50%) adenosarcomas, 1 leiomyoma with limited experience, and 1 of 10 (10%) leiomyomas. The uterine sarcomas express c‐kit, like GISTs. It seems that KIT may have a significant role in the oncogenesis of mesenchymal tumours of the uterus and ovary.

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.

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.

Serous papillary adenocarcinoma and adult granulosa cell tumor in the same ovary. An unusual case.

Surface epithelial‐stromal cell tumors are the most common neoplasms of the ovary but occurrence of a serous adenocarcinoma and an adult granulosa cell tumor in the same ovary is an unusual incident. In the present case report we describe this very uncommon occurrence in the ovary of a 50‐year‐old woman. The patient suffered abdominal distention and was referred to the state hospital where a 5×3 cm multilocular cystic lesion was observed on abdominal CT. Total abdominal hysterectomy with salpingo‐oophorectomy and omentectomy was performed. Microscopy revealed an adult granulosa cell tumor and a serous papillary adenocarcinoma in the left ovary. Immunohistochemical staining with inhibin α and pancytokeratin confirmed the diagnosis.

Tenascin expression in normal, hyperplastic, and neoplastic endometrium.

Tenascin (TN) is an extracellular matrix glycoprotein (ECM) that participates in embryogenesis and carcinogenesis. The aim of this study was to investigate immunohistochemically the expression of TN in the normal, hyperplastic, and neoplastic endometrium (endometrial adenocarcinoma). In the adenocarcinomas, the results were correlated with patient age, menopausal status, stage, grade, myometrial invasion, and vascular invasion. TN expression was studied in the following cases: proliferative endometrium (10 cases), early secretory endometrium (10), secretory endometrium (10), simple hyperplasia (15), complex hyperplasia (15), atypical hyperplasia (15), and endometrial adenocarcinomas (25). Staining of basal membranes and the cytoplasm of the stromal and epithelial cells was evaluated semiquantitatively. Positive staining was observed in the vascular and glandular basal membranes, stromal cells, and epithelial cells of proliferative, hyperplastic, and neoplastic endometrium. The difference in percentage of stained stromal cells between the neoplastic and the nonneoplastic (proliferative and hyperplastic) endometrium was significant (p<0.005). However, the percentage of stained epithelial cell area in hyperplasia was significantly higher than that of adenocarcinoma and functional endometrium (p<0.005). We conclude that TN is an extracellular matrix glycoprotein that plays a role in proliferation and possibly endometrial carcinogenesis.

Distribution of N-cadherin in human cerebral cortex during prenatal development.

An important subgroup of adhesion molecules is the superfamily of cadherins, which takes part in cell recognition and differentiation during development. To our knowledge only one study describing N-cadherin expression in developing human brain has been performed so far. Our aim is to identify N-cadherin expression to establish a relationship between its expression and function in human cerebral cortex during prenatal development. In the present study, localization and intensity of N-cadherin was investigated in developing cerebral cortex. Fetuses from spontaneous abortions (n=13) were obtained from first, second, and third trimesters. Western blot analysis revealed three bands and the third trimester samples showed the strongest bands for N-cadherin. Cell processes, axon bundles, and some of the developing neurons revealed immunoreactivity for N-cadherin throughout pregnancy. The immunoreactivity increased in the developing neocortex and expanded from the ventricular layer toward the marginal zone as development progressed. Moreover, the immunoreactivity was strong in vascular endothelium during all three trimesters. We conclude that N-cadherin is dynamically related to the organization of cerebral cortex layers during prenatal development. The dynamic expression pattern implicates N-cadherin as a potential regulator of cell migration, axon extension and fasciculation, the establishment of synaptic contacts, and neurovascular angiogenesis in the developing human cerebral cortex.

Evaluation of a Fetus with Neu-Laxova Syndrome through Prenatal, Clinical, and Pathological Findings

We report a case of Neu-Laxova syndrome in a fetus at 22 weeks with the ultrasonographic findings of characteristic facial findings, limb contractures, kyphosis and polyhydramnios. Pathological and ultrasonographic studies are discussed.

Placental biopsy by frozen section: Does it have a role in evaluation of fetal well‐being?

Aim:  To assess the effectiveness of post‐partum placental biopsy and frozen section evaluation in diagnosing pregnancy disorders.