Primary ovarian mucinous carcinoma of intestinal type: significance of pattern of invasion and immunohistochemical expression profile in a series of 31 cases.

Primary ovarian mucinous carcinomas of the intestinal type are uncommon and earlier reports have included cases diagnosed according to older, less stringent, criteria (which would now be considered borderline tumors) and variable numbers of cases of metastatic adenocarcinoma. This study was conducted to identify all cases of primary mucinous carcinoma of the ovary in a population-based registry, diagnosed according to WHO 2003 criteria, and to characterize their histologic features, immunohistochemical expression profile, and outcome. Thirty-one cases of primary ovarian mucinous carcinoma were included in this study. Immunostaining for 33 markers was performed. Mean age of the patients was 55.4+/-13.5 years. Thirty tumors were stage I or II at presentation. Twenty-six of 31 (83.9%) tumors had expansile stromal invasion, 4 of 31 (12.9%) showed destructive invasion, and 1 of 31 (3.2%) had anaplastic carcinoma in a mural nodule. All cases with destructive invasion showed grade 3 nuclear atypia whereas only 3 of 26 (11.5%) cases with expansile invasion had grade 3 nuclear atypia (P=0.0003). At follow-up, 6 of 26 patients (23.1%) with tumors showing expansile invasion experienced a recurrence, compared with 1 of 4 patients (25%) with destructive invasion and the single patient (100%) with anaplastic carcinoma. There was CK7 positivity in 26 of 31 cases (86.7%), and CK20 and Cdx-2 were each positive in 33.3% of cases. D2-40, calretinin, mesothelin, CA-125, Pax-8, TTF, and WT1 were completely negative in all cases. NHERF1 staining was present in 19 of 26 cases (73%) and its expression was associated with poor prognosis (P=0.05). Our findings support current diagnostic criteria for primary ovarian mucinous carcinoma, that is, the presence of expansile invasion, in the absence of destructive invasion, warrants a diagnosis of carcinoma. A large majority of mucinous carcinomas show only an expansile pattern of invasion and are confined to the pelvis at diagnosis.

C-kit Mutations in Endometrial Cancer: Correlation with Tumor Histologic Type.

OBJECTIVE: Endometrial cancer is the fourth most common cancer among women in developed countries. Affected patients may benefit from systemic chemotherapy, alone or in combination with targeted therapies if the disease is clinically diagnosed prior to expansion and metastasis to other organs.The aim of this study was to evaluate the prognostic role of c-kit mutations and comparision with tumor type and grade in human uterine endometrial carcinomas. MATERIALS AND METHODS: Seventy five patients with endometrial carcinoma and seventy five normal controls were studied for possible mutations in exon 17 of the c-kit gene using single strand conformational polymorphisms and sequencing. RESULTS: c-kit mutation in exon 17 appeared to be significantly different between endometrial carcinoma and normal endometrium. The pattern and frequency of the mutations was also shown to be different between tumors from different stages.

Role of exon 7 PTEN Gene in Endometrial Carcinoma.

BACKGROUND: Endometrial carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in Iranian women after breast, colorectal and lung cancers. Various genetic alterations appear to be early events in the pathogenesis of endometrial carcinoma and it seems that PTEN is the most commonly mutated gene in the endometrioid subtype. The aim of the present study was to investigate the correlation between mutations in exon 7 of PTEN gene and endometrial carcinoma. MATERIALS AND METHODS: Seventy-five patients with endometrial carcinoma and 75 females whose underwent hysterectomy for non tumoral indication were selected for evaluation of PTEN mutations in exon 7 by PCR-SSCP and sequencing. Correlations between the frequency and type of mutation and the pathologic findings of the cancer (tumor subtype, stage and grade) were assessed. RESULTS: All of the samples were obtained from Iranian patients. 60 % (45 cases) of the tumors were endometriod and 40% (30 cases) were of serous type. The grade distributions of the 75 cases according to the FIGO staging system were as follows: low grade, 20 cases; high grade 55 cases, low stage, 41 cases; high stage 34 cases. For exon 7 of the PTEN gene, the analysis showed that there were no mutations in our cases. CONCLUSIONS: Our findings in the present study suggest that exon 7 of PTEN does not play any significant role in the development of endometrial carcinoma in Iranian cases.

Expression of androgen receptors in benign and malignant endometrial stromal neoplasms.

Several studies have shown that endometrial stromal neoplasms express estrogen and progesterone receptors (ER, PR). To our knowledge, the presence or absence of androgen receptors (AR) in these rare uterine neoplasms has not been investigated. Tumors ( n=20)-3 endometrial stromal nodules, 14 low-grade endometrial stromal sarcomas (ESS, low grade), and 3 high-grade endometrial sarcomas (undifferentiated endometrial sarcoma, UES)-were studied. Immunohistochemical analyses for ER, PR, and AR were performed on formalin-fixed, paraffin-embedded archival material. Positive immunoreactions for ER and PR were observed in 14 (70%) and 17 (85%) cases, respectively. Furthermore, 9 cases (45%) were positive for AR. Among 17 ESS and UES cases, 7 (41%) revealed positivity for AR. Two of three benign stromal nodules were also positive for AR. Moreover, one of the three high-grade sarcomas (undifferentiated endometrial sarcoma) was negative for both ER and PR, but showed positive reaction for AR. In summary, ARs are expressed in 45% of endometrial stromal neoplasms. In addition to determination of ER and PR, the results of immunohistochemical examination of AR in these rare uterine tumors may have some impact on the postoperative management of the patients.

Intramedullary spinal cord ganglioglioma presenting with abnormal abdominal wall movement. Case report.

The authors present a case of intramedullary ganglioglioma in a 6-year-old girl. Since the age of 4 months the patient had experienced a spontaneous wavy undulating movement of her anterior abdominal wall resembling a severe peristalsis. The movement was continuous even during sleep, and this symptom was named "belly dance." Magnetic resonance images revealed an intramedullary tumor with ill-defined borders, and the lesion was partially resected. The patient made a good recovery, although 4 years postsurgery her scoliosis had progressed.

Antiproliferative effect of metformin on the endometrium--a clinical trial.

BACKGROUND: Unopposed estrogen has a central role in development of endometrial benign, premalignant and malignant lesions. The aim of this study was to evaluate the anti-estrogenic effect of metformin on endometrial histology in comparison with progesterone. MATERIALS AND METHODS: A total of 43 patients who were referred to our center for abnormal uterine bleeding and had a histologic diagnosis were disordered proliferative endometrium or simple endometrial hyperplasia were included and randomly distributed in two groups treated with metformin (500mg Bid) or megestrol (40mg daily), respectively, for three months. After this period the patients were evaluated by another endometrial biopsy to assess the impact of the two drugs in restoring normal endometrial histology. RESULTS: Our findings revealed that metformin could induce endometrial atrophy in 21 out of 22 patients (95.5%) while this positive response was achieved in only 13 out of 21 patients (61.9%) in the megstrol group. In addition two low grade endometrial carcinomas in the metformin group responded very well. CONCLUSIONS: We conclude that metformin could be used as an effective antiestrogenic agent in control of abnormal endometrial proliferative disorders.

The polymorphism of hypoxia-inducible factor-1a gene in endometrial cancer.

BACKGROUND: Endometral carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in women after breast, colorectal and lung cancers Hypoxia-inducible factor -1 (HIF-1) is a key transcription factor that regulates cellular response to hypoxia HIF-1 plays important roles in the development and progression of cancer through activation of various genes that are involved in crucial aspects of cancer biology, including angiogenesis, energy metabolism, vasomotor function, erythropoiesis, and cell survival. In this study, we aimed to investigate the association between HIF-1 1772 C/T polymorphisms and endometrial cancer. MATERIALS AND METHODS: 75 patients with endometrial carcinoma and 75 patients whose underwent hysterectomy for non tumoral indication selected for evaluation of HIF-1 1772 C/T polymorphisms by PCR-RFLP and sequencing. RESULTS: For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with endometrial cancer risk. CONCLUSIONS: Our results suggest that the C1772T polymorphism of the HIF-1a may be associated with endometrial cancers.

Polymorphism of p53 gene codon 72 in endometrial cancer: correlation with tumor grade and histological type.

BACKGROUND: Endometrial cancer is the fourth most common cancer among women in developed countries. Patients with endometrial cancer may benefit from systemic chemotherapy alone or in combination with targeted therapies if the disease is clinically diagnosed prior to spread and metastasis to other organs. The aim of this study was to evaluate the prognostic role of p53 polymorphism and its correlation with tumor grade in human uterine endometrial carcinomas. MATERIALS AND METHODS: A total of 75 patients with endometrial carcinomas were studied for possible mutations in exon 4 of the p53 gene using polymerase chain reaction and restricting fragment length polymorphism techniques and sequencing. RESULTS: In recent study, The rate of homozygote genotype of pro/pro or Arg/Arg in high grade group was higher than in comparison with low grade one. In addition samples that were undigested in RFLP, showed mutation in exone 4. CONCLUSIONS: Our findings showed that high grade endometrial carcinomas are highly associated with TP53 polymorphisms in comparison with low grades.

A pilot study on image analysis techniques for extracting early uterine cervix cancer cell features.

The second most common and preventable form of cancer among women worldwide is cervical cancer in which the signs for this disease can be detected in the early Pap smear screening of cervical cells. To improve the efficiency of expert diagnosis, we will need to automate the feature extraction of cervical cancer cells by the means of image processing techniques. This article employs image processing techniques to get the special features of normal, precancerous and cancerous cell images. We extract spectral features for cervical cancer cell detection. This article uses the noise decrease filters, OTSU threshold to make it ready for processing through 2-D Fourier and logarithmic transforms. By drawing the linear plot, we will be able to extract the feature of normal, precancerous and cancerous cells according to the texture and morphology automatically. These linear plots will be unique which can separate the cells in three groups of normal, precancerous and cancerous cells. This separation is done with 100% accuracy due to the unique linear plots. The experiment shows that extracted unique features for each cell will provide evidences for diagnoses even in cytopathology images in which the nucleus and cytoplasm segmentation algorithms suffer from complex overlaying cells.

Malignant endometrial polyps: Report of two cases and review of literature with emphasize on recent advances.

Endometrial polyps are common pathologic findings in gynecologic pathology practice. Although malignant changes in these lesions are uncommon, numerous studies confirmed this association especially with endometrial serous and clear cell carcinoma. Two cases of malignant endometrial polyps in association with presumed precursor lesion in one of them are presented.

Inverse correlation of secreted frizzled-related protein 4 and beta-catenin expression in endometrial stromal sarcomas.

Endometrial stromal sarcomas are rare uterine tumours. Whereas the histology and immunohistochemistry of these tumours are well documented, almost nothing is known about the molecular mechanisms involved in their pathogenesis. To characterize the genes altered in these malignancies, a genome-wide cDNA library was generated by suppression subtractive hybridization and a set of differentially expressed clones was isolated. These were then used to produce custom-spotted cDNA arrays. Genes deregulated in endometrial stromal sarcomas were identified by cDNA array hybridization and were confirmed by quantitative real-time PCR analyses and in situ hybridization. Following cDNA array analysis, more than 300 genes deregulated in endometrial stromal sarcoma were selected and sequenced. Among the most significantly deregulated genes were those of secreted frizzled-related proteins (SFRPs), in particular secreted frizzled-related protein 4 (SFRP4). SFRPs are putative modulators of the Wnt-signalling pathway and play a role in different cellular events including cell proliferation. Compared with normal endometrium, the expression of SFRP4 was decreased in both low-grade endometrial stromal sarcoma (ESS; n = 10) and undifferentiated endometrial sarcoma (UES; n = 4), being lower in the latter more aggressive form. These results were verified on paraffin wax-embedded tissue by quantitative real-time PCR analysis and in situ hybridization. Furthermore, the expression of beta-catenin, an important component of the Wnt-signalling pathway, was regulated in an opposite manner to SFRP4, being particularly increased in undifferentiated sarcomas. The activation of the Wnt-signalling pathway was additionally supported by the immunohistochemical demonstration that beta-catenin was translocated to the nucleus in UES. SFRP4 may therefore be a putative tumour suppressor involved in deregulation of the Wnt pathway and in the pathogenesis of ESS and UES.