Gulgun Erdogan

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.

Stage I small cell carcinoma of the endometrium: survival and management options

Small cell carcinoma (SCC) of the endometrium is a rare but aggressive disease with early systemic involvement. Patient survival is short. To date, no effective treatment protocol has been established. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. The case of a patient with stage IB endometrial SCC is presented with an overview based on all reported cases of SCC of the endometrium and its treatment with particular reference to stage I cases.

Proliferating activity in differential diagnosis of benign phyllodes tumor and cellular fibroadenomas: is it helpful?

Benign phyllodes tumors and fibroadenomas are two types of fibroepithelial tumors of breast that are usually difficult to differentiate. The purpose of this study is to evalute the proliferative activity of these tumors and to find out if it helps in differential diagnosis. Thirty-one benign phyllodes tumors and twelve cellular fibroadenomas were retrieved from the archives of Pathology Department of Akdeniz University, School of Medicine. Proliferating activity of epithelial and stromal cells were evaluated by using labeling index (LI) of proliferating cell nuclear antigen (PCNA) and Ki-67 antigen by immunohistochemistry. The results were compared with other clinicopathologic findings. There was not any significant difference between the proliferating activity of phyllodes tumor and cellular fibroadenomas. Mean LI of PCNA was 28.01 (±22.85) in stromal cells and 56.57 (±30.98) in epithelial cells of phyllodes tumor where it was 28.92 (±24.02) and 62.53 (±32.56) in fibroadenomas. Ki-67 indices were 0.05 (±0.19) in stromal cells, 2.65 (±12.53) in epithelial cells of phyllodes tumors and 0.0 (±0) in stromal cells, 0.43 (±0.63) in epithelial cells of fibroadenomas. There was no correlation between the diameter of tumors and proliferating activity in both groups. Proliferating activity, determined by immunohistochemistry with PCNA and Ki-67 antibodies did not reveal significant difference between phyllodes tumor and fibroadenoma.

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.

Expression of c-erbB-2 and p53 in breast carcinoma patients: comparison with traditional prognostic factors and survival.

We aimed to determine the correlations between standard clinicopathological factors and expression of c-erbB-2 and p53 proteins, and to investigate the significance of these variables in relapse and disease-free survival (DFS) in breast carcinoma patients. Data from 200 patients who had undergone mastectomy for breast carcinoma were evaluated. Significant correlations were found between c-erbB-2 positivity and high histological grade (grade 3) tumour, p53 positivity and high grade tumour, and age < 60 years and oestrogen receptor negativity. Twenty-six patients (13%) developed a recurrence. Disease relapse was more frequent in patients who had axillary lymph node (ALN) metastasis, high grade tumour, c-erbB-2 positivity and p53 positivity; these variables were also associated with a shorter DFS. The effects of ALN metastasis and p53 positivity were significant. In conclusion, ALN metastasis and p53 positivity were important factors for predicting disease relapse in mastectomy-treated breast carcinoma patients; other clinicopathological criteria and c-erbB-2 positivity were not predictive.

Ovarian ependymoma. Case report

A 76‐year‐old woman presented with a large calcifying mass behind the bladder. The tumor contained solid areas of a yellowish white color. Microscopic examination revealed highly cellular solid areas with many typical ependymal perivascular pseudorosettes. The cells contained uniform round‐to‐oval nuclei, some of which had irregular contours, clumped chromatin and occasional prominent nucleoli. There was widespread geographic necrosis and there were 5 atypical mitotic figures per 10 high power fields. Glial fibrillary acidic protein (GFAP) immunopositivity was observed in the cytoplasm of the tumor cells. Based on the histopathologic and immunohistochemical features, the tumor was diagnosed as an anaplastic ependymoma. This is to the best of our knowledge only the second case of anaplastic ependymoma in the medical literature.

Detection of precancerous cervical conditions using elastic light single-scattering spectroscopy

We have investigated the potential application of elastic light single-scattering spectroscopy (ELSSS) as an adjunctive tool for screening of cervical precancerous lesions non-invasively and in real time. Ex-vivo measurements were performed on 95 cervix biopsy tissue of 60 patients. Normal cervix tissue from 10 patients after hysterectomy was used as a control group. Correlation between ELSSS spectra and histopathology results were investigated. It was found that the spectral slope was positive for all the spectra taken on normal cervix tissue samples from the control group. We assumed that if there is only one spectrum with a negative spectral slope among the all spectra taken on a biopsy specimen, the biopsy specimen is pathologically abnormal. This shows that pap smear and ELSSS results are in good agreement. Most biopsy tissue samples had both positive and negative spectral slopes. Therefore, we calculated the percentage of negative spectral slopes and hypothesized that this was correlated to dysplastic percentage of the epithelial tissue of the biopsy material. The ROC curve was calculated using the dysplastic percentage and high squamous intraepithelial lesion (HSIL) and low squamous intraepitherlial lesions (LSIL) biopsy specimens were differentiated from non HSIL and LSIL with a sensitivity and specificity of 70.4% and 66.7% respectively, with p < 0.05.

Extramedullary hematopoiesis mimicking acute appendicitis: a rare complication of idiopathic myelofibrosis

Extramedullary hematopoiesis (EMH) is rarely found in the gastrointestinal tract. To our knowledge, EMH involving the appendix was not described. We report a case with a previous history of idiopathic myelofibrosis, which presented with clinical findings of acute appendicitis that necessitate appendectomy after the relief of his anemia. Microscopic examination and immunohistochemistry revealed foci of EMH throughout the mucosa and the submucosa. In the latter, small clusters of hematopoietic cells were also detected in a few dilated vascular structures. The histopathological features of acute appendicitis were not observed. Our case supports that EMH might develop in organs that are not involved in hematopoiesis. Although in gastrointestinal system, obstruction and bleeding are the most common symptomatic manifestations, this case emphasizes that EMH might also present clinically as acute appendicitis. The absence of histopathological features of acute appendicitis raises the possibility that local production of some mediators from hematopoietic precursor cells might contribute to this clinical presentation.

Diagnosis abnormal cervical tissue by elastic light scattering spectroscopy and correlation with the results of Pap-smear examination

We have investigated the potential application of elastic light single-scattering spectroscopy in detection of cervical precancerous lesions non-invasively and in real time. Ex-vivo spectroscopic measurements were performed on 95 cervix biopsy tissue of 60 patients. Normal cervix tissue from 10 patients after hysterectomy was used as a control group. It was found that the spectral slope was positive and negative for the spectra taken on normal cervix and precancerous cervix tissue respectively. Sign of the spectral slopes were used as a parameter to differentiate normal cervix tissue from dysplastic cervix tissue. Elastic light single-scattering spectroscopy measurements in defining cervical tissue were 100% consistent with Pap-smear results.