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.

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.

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.

No abstract

Background/Aims: The role of human papillomavirus (HPV) in the etiology of cervical cancer is now well established. This investigation was designed to study the prevalence of the four most common high-risk HPVs in the archival tissues with precancerous and cancerous lesions from patients from northwestern Iran. Methods: 133 formalin-fixed paraffin-embedded tissue specimens were tested for HPV DNA by using GP5+/6+-based general PCR and two type-specific PCRs. Results: In total, 84 (64%) out of 131 amplifiable samples were positive for HPV DNA. The most prevalent oncogenic HPV was type 16 (67.6%) followed by types 31 (22.8%), 18 (7.6%) and 33 (1%). Multiple HPV infections were present in 20 (15.3%) of the 131 samples. Notably, of these 20 cases with multiple infections, 15 were from patients with invasive cervical cancer. Conclusions: The multiplicity of HPV genotypes was noted in invasive cervical carcinoma samples, along with rather different circulating HPV types in the study population. Hence, relevant HPV typing information in cervical carcinoma is very important for planning more efficient screening programs and for further HPV vaccine design.

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.

No abstract

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.