Ovarian Surface Epithelial Tumors Research Articles

The Incidence and Extent of Mullerian Metaplasias in Ovarian Surface Epithelial Tumors

Objectives: Most ovarian surface epithelial tumors emerge from a background of Mullerian metaplasias. The incidence and extent of Mullerian metaplasias were examined in ovarian surface epithelial tumors. Methods: The incidence of Mullerian metaplasias was evaluated according to the presence of the metaplasias in all cases. The extent of these metaplastic changes was scored from (1+) to (4+) according to the extended area in all tumoral slide sections. Results: Ciliated cell metaplasia was found in 80.4 % of benign tumors, 100 % of borderline tumors and 93.3 % of malignant tumors. Eosinophilic cell metaplasia was present in 13 % of benign tumors, 70 % of borderline tumors and 93.3 % of malignant tumors. Clear cell metaplasia was observed in 17.4 % of benign tumors, 20 % of borderline tumors and 40 % of malignant tumors. While ciliated cell metaplasia was more frequent and extensive in benign tumors, eosinophilic and clear cell metaplasias were more frequent and extensive in borderline and malignant tumors (p

A case of ovarian large cell neuroendocrine carcinoma

Large cell neuroendocrine carcinoma (LCNEC) of the ovary is a rare entity and is frequently associated with ovarian surface epithelial tumors. Since Collins et al. described the fi rst case of mixed neuroendocrine and mucinous carcinoma, a few more cases of primary ovarian LCNECs have been reported. The prognosis of LCNECs is generally very poor even when the diagnosis is made at an early stage. A 40-year-old woman presented with a pelvic mass measuring 30 cm in diameter. She underwent an exploratory laparotomy for resection of the pelvic mass and staging if needed. After the operation, she was diagnosed of stage Ia LCNEC associated with mucinous tumor (including benign, borderline, malignant tumor) of left ovary. The patient received six cycles of paclitaxel-carboplatin chemotherapy postoperatively. There have been no signs of local tumor recurrence or metastasis at followup examinations during the fi rst 8 months after the operation.

Rare Tumors of Ovary: Case Report and Literature Review

Introduction: Large cell neuroendocrine carcinoma (LCNEC) or non small cell neuroendocrine carcinoma the ovary is a rare entity and is frequently associated with ovarian surface epithelial tumors. However, its association with serous carcinoma is rarer, in our knowledge tree cases has been described in international literature and the first case in Moroccan literature. Case Report: A 54-year-old woman presented with a pelvic mass measuring 15 cm in diameter. She underwent an exploratory laparotomy with resection of the pelvic mass. Diffuse and nodular intra-abdominal disseminations were observed. Immunohistochemistry stain confirmed the diagnosis of large cell neuroendocrine carcinoma with serous carcinoma. The patient received three courses of carboplatin and paclitaxel and she's still alivewith a decline of 6 months. Its clinicopathologic association is discussed and the literature is reviewed. Conclusion: In summary, ovarian LCNEC is an aggressive tumor with a tendency to present at advanced stage and cause death within a mean of 17 months after diagnosis; however, some patients, particularly those with stage I disease and/or those who have received platinum-based therapy, may have a more favorable prognosis.

Weapons Ovarian Epithelial Tumors May Use in Immune Escape: An Immunohistochemical Correlational Study

Investigate FasL and survivin expression in a series of primary ovarian surface epithelial tumors, correlate their expression with each other, and characterize the presence of CD3+ T-lymphocytes in studied tumors and determine whether their presence correlates with FasL or survivin expression in malignant cases. FasL and survivin expression was assessed in 54 ovarian epithelial tumors. The results were compared between different tumor types and grades. Correlation between both markers' expression in all studied tumors was done. Either marker's expression was compared to the mean CD3+ T-lymphocytes per HPF in the studied malignant tumors. Either FasL or survivin expression was significantly higher in malignant versus benign ovarian epithelial tumors (p < 0.001 for both) and both markers were strongly correlated to each other (r = 0.877 & p < 0.001). Malignant tumors show significantly higher mean CD3+ T-lymphocytes than benign and borderline tumors. The mean CD3+ T-lymphocytes decrease significantly on increasing malignant tumor grade (p = 0.019) and expression of both FasL and survivin (r = -0.729, -0.582, respectively & p < 0.001 for both). The higher expression of FasL and survivin in malignant as compared to benign ovarian tumors suggest that they have a significant role in pathogenesis of ovarian carcinoma. Both markers are strongly correlated to each other and may contribute to immune escape of ovarian carcinoma as their higher expression is associated with decreased number of CD3 + T-lymphocytes.

Diffusion-weighted MRI: a useful technique to discriminate benign versus malignant ovarian surface epithelial tumors with solid and cystic components

To evaluate differences in apparent diffusion coefficient (ADC) values for the solid component of benign and malignant ovarian surface epithelial tumors with the goal of differentiating benign versus malignant ovarian tumors preoperatively. A total of 127 patients with 131 pelvic masses identified by ultrasound between January 2006 and January 2011 were enrolled in this study. 46 patients were diagnosed with benign tumors, and 85 patients were diagnosed with malignant pathologies. For all of the patients, routine spin-echo MRI and diffusion-weighted imaging were performed. ADC values were determined for all of the masses, and the mean ADC values for the benign and malignant tumors were analyzed using Student's t test. A P value <0.05 was considered statistically significant. Mean ADC values associated with malignant ovarian surface epithelial tumors were significantly lower than the mean ADC values of the benign tumors. In addition, the range of ADC values associated with a 95% confidence interval did not overlap between the two groups. ROC analysis indicated that a cutoff ADC value of 1.25 × 10(-3) mm(2)/s was associated with 90.1% sensitivity and 89.9% specificity. ADC values determined from 1.5 T MR DWI of benign and malignant ovarian masses were found to be significantly different.

Mutational Analysis (c.402C&gt;G) of the FOXL2 Gene and Immunohistochemical Expression of the FOXL2 Protein in Testicular Adult Type Granulosa Cell Tumors and Incompletely Differentiated Sex Cord Stromal Tumors

Recently a somatic point mutation in the FOXL2 gene has been characterized in ovarian adult type of granulosa cell tumor (ATGCT) (94.6%), thecomas (12.5%), but not in juvenile type of ovarian granulosa cell tumor, other ovarian sex cord tumors and ovarian surface epithelial neoplasms. Whether this mutation is present in testicular ATGCT or incompletely differentiated sex cord stromal tumor (ISCST) is not known. Four ATGCTs, 4 ISCST were immunohistochemically investigated with anti-FOXL2 and 3 ovarian ATGCTs were used as positive control. Weak-to-moderate immunoreactivity was found in all tested testicular and ovarian tumors. PCR and direct sequencing were used for detection of c.402C>G of the FOXL2 gene. No mutation was found in any of the testicular ATGCTs or ISCSTs whereas all ovarian tumors showed the c.402C>G point mutation of the FOXL2 gene. On the basis of this small series of these rare testicular neoplasms, it seems that the c.402C>G mutation of the FOXL2 gene frequently found in adult type of ovarian GCT does not play any significant role in the development of ATGCT and ISCST.

Ovarian enzymatically active stromal cells can be a promoter of ovarian surface epithelial tumor

Surface epithelial tumors (SETs) are the most common neoplasms of the ovary. They are traditionally thought derived from the ovarian surface or, as a recent hypothesis suggests, from various sources outside of ovary. Enzymatically active stromal cells (EASCs) are scattered in stroma of ovary, and characterized by their steroid-producing ability. With my observation of the increased EASCs near the epithelial cells of SETs, I hypothesize the epithelial cells of SETs can cause the increase of EASCs by converse adjacent stromal cells to EASCs; and EASCs, as a positive feedback, can prompt the proliferation of their neighbouring epithelial cells of SETs by secreting steroid hormone.

Mucinous cystadenocarcinoma of the testis: a case report

We present a rare case of unilateral intratesticular cystadenocarcinoma with mucinous differentiation in a 71-year-old male patient. The orchiectomy specimen revealed a 3.5-cm well to moderately differentiated cystic neoplasm with elongated fine papillary structures lined by columnar epithelium with alternating goblet and ciliated cells completely replacing the testicular parenchyma. Immunohistochemical studies showed positivity for cytokeratin 20, carcinoembryonic antigen, and mucin 2, and negativity for cytokeratin 7, mucin 5AC, vimentin, thyroid transcription factor 1, Wilms' tumor 1, and cancer antigen 125. The current case shows a focal cyst-lining component with benign appearance. Imaging studies and colonoscopy showed no evidence of other suspicious lesions. This tumor resembles morphologically to an intestinal-type ovarian surface epithelial tumor.

Alternate mucoid and hyalinized stroma in clear cell carcinoma of the ovary: manifestation of serial stromal remodeling

The stroma in ovarian clear cell carcinoma often shows alternate mucoid and hyalinized change. The hyalinized stroma is recognized to be an aberrant deposition of basement membrane material produced by tumor cells. The mucoid stroma, however, has drawn far less attention, and its significance remains unclear. We examined 60 ovarian clear cell carcinomas for the distribution and nature of the mucoid stroma. For comparison, 125 other surface epithelial ovarian tumors were examined. Twenty-nine of 60 (48%) clear cell carcinomas showed a mucoid stroma, either focally (21 cases) or diffusely (8 cases). The mucoid stroma in clear cell carcinomas was distinct from that in other surface epithelial tumors as follows: it showed a compact spherule-like appearance, commonly occupying the cores of small papillae. It also exhibited a cribriform pattern, resembling that of adenoid cystic carcinoma. It was rarely associated with stromal cells, despite the presence of abundant glycosaminoglycan including hyaluronan. Alternatively, it was strongly associated with hyalinized stroma. Among 40 clear cell carcinomas that had at least one type of stroma, 26 (65%) had both, either concomitantly or separately. The mucoid stroma tended to attenuate if the hyalinized stroma developed. In vitro, a clear cell carcinoma cell line, HAC-2, formed a spherule-like structure containing hyaluronan in the center, and a significant amount of hyaluronan was detected by latex agglutination immunoturbidimetry, indicating that HAC-2 itself has the potential to produce hyaluronan. All of these facts indicate that the spherule-like mucoid stroma and hyalinized stroma represent different phases of the stromal remodeling process, which is promoted by the deposition of different extracellular matrices produced by clear cell carcinoma cells. The spherule-like mucoid stroma and hyalinized stroma are considered complementary diagnostic signatures of ovarian clear cell carcinoma.

Cell Type–Specific Targeted Mutations of Kras and Pten Document Proliferation Arrest in Granulosa Cells versus Oncogenic Insult to Ovarian Surface Epithelial Cells

The small G-protein KRAS is crucial for mediating gonadotropin-induced events associated with ovulation. However, constitutive expression of KrasG12D in granulosa cells disrupted normal follicle development leading to the persistence of abnormal follicle-like structures containing nonmitotic cells. To determine what factors mediate this potent effect of KrasG12D, gene profiling analyses were done. We also analyzed KrasG12D;Cyp19-Cre and KrasG12;Pgr-Cre mutant mouse models that express Cre prior to or after the initiation of granulosa cell differentiation, respectively. KrasG12D induced cell cycle arrest in granulosa cells of the KrasG12D;Cyp19-Cre mice but not in the KrasG12D;Pgr-Cre mice, documenting the cell context-specific effect of KrasG12D. Expression of KrasG12D silenced the Kras gene, reduced cell cycle activator genes, and impaired the expression of granulosa cell and oocyte-specific genes. Conversely, levels of PTEN and phosphorylated p38 mitogen-activated protein kinase (MAPK) increased markedly in the mutant granulosa cells. Because disrupting Pten in granulosa cells leads to increased proliferation and survival, Pten was disrupted in the KrasG12D mutant mice. The Pten/Kras mutant mice were infertile but lacked granulosa cell tumors. By contrast, the Ptenfl/fl;KrasG12D;Amhr2-Cre mice developed aggressive ovarian surface epithelial cell tumors that did not occur in the Ptenfl/fl;KrasG12D;Cyp19-Cre or Ptenfl/fl;KrasG12D;Pgr-Cre mouse strains. These data document unequivocally that Amhr2-Cre is expressed in and mediates allelic recombination of oncogenic genes in ovarian surface epithelial cells. That KrasG12D/Pten mutant granulosa cells do not transform but rather undergo cell cycle arrest indicates that they resist the oncogenic insults of Kras/Pten by robust self-protecting mechanisms that silence the Kras gene and elevate PTEN and phosphorylated p38 MAPK.

Ovarian and Paraovarian Squamous-lined Cysts (Epidermoid Cysts): A Clinicopathologic Study of 18 Cases With Comparison to Mature Cystic Teratomas

The origin of ovarian epidermoid cyst is unknown. Sixteen ovarian and 2 paraovarian squamous-lined cysts unassociated with teratomatous elements were studied. The ovarian cysts represented 1.5% of consecutive ovarian surface epithelial tumors examined and were one-nineteenth as common as mature cystic teratoma. The mean patient age was 57 years. All tumors were unilateral and the majority were incidental findings. The mean tumor size was 1.75 cm and the median, 3.0 cm. In comparison to 120 consecutive patients with mature cystic teratoma who had a mean age of 41 years and a mean tumor size of 6 cm, the ovarian epidermoid cysts were significantly smaller and occurred at a significantly older age (P<0.01). All cysts displayed mature squamous epithelium with a granular layer, with hyperkeratosis in 14 and parakeratosis in 4. In 2 patients, there were contralateral mature cystic teratomas, and in 2 others the cysts contained rare hairs. Two displayed foci of Brenner tumor and 1 appeared to arise in endometriosis. In summary, 7 of 16 ovarian epidermoid cysts displayed features suggesting they reflected insufficiently sampled teratomas, Brenner tumors with squamous metaplasia, or a metaplastic change in endometriosis. Epidermoid cyst of the ovary as defined by histology is a heterogeneous group; pure epidermoid cyst, if it exists at all, probably represents less than 1% of ovarian surface epithelial tumors.

Selected Background Findings and Interpretation of Common Lesions in the Female Reproductive System in Macaques

The authors describe a selection of normal findings and common naturally occurring lesions in the reproductive system of female macaques, including changes in the ovaries, uterus, cervix, vagina, and mammary glands. Normal features of immature ovaries, uteri, and mammary glands are described. Common non-neoplastic lesions in the ovaries include cortical mineralization, polyovular follicles, cysts, ovarian surface epithelial hyperplasia, and ectopic ovarian tissue. Ovarian neoplasms include granulosa cell tumors, teratomas, and ovarian surface epithelial tumors. Common non-neoplastic uterine findings include loss of features of normal cyclicity, abnormal bleeding, adenomyosis, endometriosis, epithelial plaques, and pregnancy-associated vascular remodeling. Hyperplastic and neoplastic lesions of the uterus include endometrial polyps, leiomyomas, and rarely endometrial hyperplasia and endometrial adenocarcinoma. Vaginitis is common. Cervical lesions include endocervical squamous metaplasia, polyps, and papillomavirus-associated lesions. Lesions in the mammary gland are most often proliferative and range from ductal hyperplasia to invasive carcinoma. Challenges to interpretation include the normal or pathologic absence of menstrual cyclicity and the potential misinterpretation of sporadic lesions, such as epithelial plaques or papillomavirus-associated lesions. Interpretation of normal and pathologic findings is best accomplished with knowledge of the life stage, reproductive history, and hormonal status of the animal.

α-Galactosylceramide enhances the protective and therapeutic effects of tumor cell based vaccines for ovarian tumors

Ovarian cancer is one of the leading causes of death from gynecological cancers in the United States. Conventional therapies are unlikely to control advanced stage ovarian cancers, thus requiring innovative alternative therapies. In the current study, we characterized the therapeutic effect of tumor cell-based vaccines combined with the adjuvant, α-galactosylceramide (α-GalCer) using two different mouse models. Our data suggests that treatment with α-GalCer led to an increase in the IFN-γ serum levels in the presence or absence of irradiated mouse ovarian surface epithelial tumor cells (MOSEC). Furthermore, administration of irradiated MOSEC tumor cells with adjuvant α-GalCer generated significant protective and therapeutic antitumor effects against MOSEC tumors in vaccinated C57BL/6 mice. In addition, immune cells expressing CD4, CD8 or NK1.1 markers were found to be important for the protective antitumor effects generated by irradiated tumor cell-based vaccines combined with adjuvant α-GalCer. We also found that treatment of a spontaneous ovarian cancer murine model, the Müllerian inhibiting substance type II receptor T antigen (TgMISIIR-TAg) transgenic mice with ovarian tumor cell-based vaccines combined with adjuvant α-GalCer led to prolonged survival as well as increased numbers of tumor-specific CD8 + T cells. Therefore, irradiated tumor cell-based vaccines in combination with α-GalCer are capable of breaking immune tolerance and generating significant antitumor effects in two different mouse tumor models. Our study serves as a foundation for future clinical translation.

Mixed Ovarian Epithelial Carcinomas With Clear Cell and Serous Components are Variants of High-grade Serous Carcinoma

There are conflicting data about chemoresistance and prognosis in ovarian clear cell carcinoma (CCC). This could be due to significant interobserver variation in the diagnosis of CCC and other ovarian surface epithelial tumors containing clear cells. Thirty-two cases previously diagnosed as CCC, high-grade ovarian serous carcinoma (SC), and mixed surface epithelial carcinoma (SEC) with clear cell and serous components were reviewed by 4 gynecologic pathologists blinded to the original diagnoses. Interobserver reproducibility was evaluated. Each case was also assessed using immunohistochemical markers Wilm tumor 1, estrogen receptor, and p53. The interobserver reproducibility was greatest for pure CCC (kappa of 0.82), and lowest for the mixed SEC (kappa of 0.32). Moderate agreement was seen in the pure SC category (kappa of 0.59). All pure SC and most mixed SEC presented as stage III or IV diseases. Most pure CCC presented as stage I or II diseases. Immunoreactivities of the mixed SECs were similar to those of pure SC, but significantly different from those of pure CCC for Wilm tumor 1 (P=0.0011 for both components), estrogen receptor (P=0.0003 for clear cell component, P=0.0001 for serous component), and p53 (P=0.0062 for both components). The serous and clear cell components of mixed SEC showed higher mitotic rates than pure CCC (P=0.004 and P=0.023, respectively), but the mitotic rate of pure SC was similar to the mixed SEC. We conclude that (1) pure CCC is reproducibly diagnosed. (2) The diagnosis of mixed ovarian SEC with clear cell component is not reproducible. (3) Mixed SEC with clear cell and serous components show similar stage, mitotic activities, and immunoreactivities to those of pure SC, and likely represent SC with clear cell changes.

Oncofetal Protein Glypican-3 Distinguishes Yolk Sac Tumor From Clear Cell Carcinoma of the Ovary

Clear cell carcinoma (CCC) of the ovary is the surface epithelial neoplasm most often confused with primitive germ cell tumors, particularly yolk sac tumor (YST) and dysgerminoma. OCT3/4 has proven to be a sensitive and relatively specific marker for the latter entity, but existing markers for YST are limited. Recent studies suggest that glypican-3 (GPC3), an oncofetal protein expressed in fetal liver and malignant tumors of hepatocytic lineage, is also expressed in germ cell tumors, particularly YST. To investigate whether GPC3 is useful in distinguishing YST from ovarian CCC, we studied the expression of GPC3 in a large series of ovarian neoplasms and compared it to the expression profiles of CK7 and alpha-fetoprotein. Tissue microarrays containing over 400 benign and malignant ovarian neoplasms, including 34 CCCs were stained with monoclonal GPC3 (clone 1G12, Biomosaics, Burlington, VT). These arrays contained a wide assortment of ovarian surface epithelial neoplasms and sex cord stromal neoplasms, as well as germ cell tumors. Full paraffin tissue sections from 32 YSTs and 10 CCCs were also assessed. All but one YST (97%), including those associated with mixed germ cell tumor were positive for GPC3, whereas all teratomas and embryonal carcinomas were negative. Both cytoplasmic and membrane staining were present in the positive cases, with no background staining. The syncytiotrophoblastic cells in the germ cell tumors and placental villi included in the arrays were also positive for GPC3. Most CCCs (83%) were completely negative for GPC3, as were 99% serous, 94% endometrioid, and 100% mucinous tumors. Five CCCs exhibited focal, moderate to strong GPC3 expression and in 2 the expression was focal and weak. All other tissues, including normal ovary were negative for GPC3. GPC3 seems to be a promising diagnostic marker for differentiating YST from ovarian CCC (P < 0.0001). Because GPC3 may be associated with alpha-fetoprotein expression, further studies are required to determine the utility of GPC3 in differentiating YST from CCC with hepatoid differentiation.

Chondromatous differentiation in clear cell carcinoma of the ovary: a rare finding challenging the differential diagnosis

Ovarian surface epithelial tumors rarely have heterologous elements including bone or cartilage that may appear histologically benign or malignant. There are a few case reports in the literature of ovarian tumors containing chondromatous areas. We report a clear cell carcinoma of the bilateral ovary showing chondromatous differentiation in a 56-year-old woman. Histopathologic study of the specimen showed clear cell carcinoma with many small foci of chondromatous differentiation. Immunohistochemical studies demonstrated positivity for S-100 confirming the diagnosis. The patient was alive with disease on chemotherapy for 16 months. A rare case of benign appearing chondromatous differentiation in an ovarian clear cell carcinoma of the ovary is described, and the significance of this finding is discussed.

Immunohistochemical Analysis of Reserve Cell-Like Cells of Ovarian Müllerian Mucinous/Mixed Epithelial Borderline Tumor

Ovarian mucinous borderline tumor of müllerian type (MMBT) and mixed epithelial borderline tumor of müllerian type (MEBT) are uncommon subtypes of ovarian surface epithelial tumors. Both are often associated with endometriosis, but their histogenesis is still debated. We have noticed occasional foci of subepithelial cuboidal cells resembling uterine cervical reserve cells (RCs) in MMBTs/MEBTs, which have not been documented in the literature to the best of our knowledge. This study was carried out to identify the presence of RC-like cells (RCLCs) in MMBTs/MEBTs and their immunohistochemical features in comparison to those of cervical RCs. We analyzed 10 consecutive cases of RC-like MMBTs/MEBTs, 6 of which were associated with endometriosis. Immunohistochemistry was performed for p63, cytokeratin 34BE12, cytokeratin 17 (CK17), and low-molecular cytokeratin CAM5.2. In 9 of 10 cases, RCLCs were appreciated in hematoxylin-eosin stain, although their amount in the tumor varied from case to case. Immunohistochemically, RCLCs were positive for p63 in 9 cases. They were positive for both 34BE12 and CK17 and were very weakly positive or negative for CAM5.2 in 8 cases. This immunohistochemical profile is similar to that seen in the cervical RCs. Reserve cell-like cells were also found in the foci of endometriosis coexisting with MMBTs/MEBTs in 1 of 5 cases examined. We draw attention to the existence of the RCLCs in MMBTs/MEBTs and in endometriosis. Their similarity to the cervical RCs may indicate their potential role as precursor cell that may subsequently differentiate into different müllerian cell types, thus merit further study.

The Development of High-grade Serous Carcinoma From Atypical Proliferative (Borderline) Serous Tumors and Low-grade Micropapillary Serous Carcinoma

Recently, we have proposed a model for the development of ovarian surface epithelial tumors. In this model, all histologic types of surface epithelial tumors are divided into 2 categories designated type I and type II which correspond to 2 pathways of tumorigenesis. Type I tumors include low-grade serous carcinoma, mucinous carcinoma, endometrioid carcinoma, malignant Brenner tumor, and clear cell carcinoma which develop slowly in a stepwise fashion from well-recognized precursors, namely atypical proliferative (borderline) tumors. Type II tumors are high-grade, rapidly growing tumors that typically have spread beyond the ovaries at presentation. They include high-grade serous carcinoma ("moderately" and "poorly" differentiated), malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinoma. These tumors are rarely associated with morphologically recognizable precursor lesions and it has been proposed that they develop "de novo" from ovarian inclusion cysts. This model implies that the pathogenesis of type I and type II tumors are separate and independent but it is not clear whether some type II tumors develop from type I tumors. In this study, we attempted to address this issue by determining the clonality of 6 cases of high-grade serous carcinomas that were closely associated with atypical proliferative serous (borderline) tumors and invasive low-grade micropapillary serous carcinomas. We reviewed 210 ovarian serous tumors from the surgical pathology files of the Johns Hopkins Hospital and identified 3 high-grade serous carcinoma that were directly associated with atypical proliferative serous (borderline) tumors and 3 that were associated with invasive low-grade micropapillary serous carcinomas. A morphologic continuum between the high-grade carcinoma and the low-grade tumors was observed in 4 cases whereas in the remaining 2 cases the high-grade and low-grade components were separate. Mutational analyses for KRAS, BRAF, and p53 genes were performed on microdissected samples from the high-grade and low-grade tumor areas for each case. All 6 tumors demonstrated wild-type BRAF and p53 genes. Only 2 of the 6 cases were informative from a molecular genetic standpoint. In those 2 cases we found the same mutations of KRAS in both the atypical proliferative serous (borderline) tumor and the high-grade serous carcinoma component of the tumor, indicating a clonal relationship. The above results suggest that the majority of high-grade and low-grade carcinomas develop independently but in rare cases, a high-grade serous carcinoma may arise from an atypical proliferative serous (borderline) tumor.

Cell surface overexpression of αvβ5 integrin impedes αvβ3‐mediated migration of the human ovarian adenocarcinoma cell line IGROV1

Human ovarian surface epithelium and epithelial tumors express integrin alphavbeta5, which can interact with vitronectin. In addition, in vitro acquisition of cisplatin resistance by alphavbeta3-expressing IGROV1 cells is accompanied by cell-surface expression of integrin alphavbeta5. To further explore the role of alphavbeta5 in ovarian carcinoma cells, IGROV1 cells were stably transfected with a human beta5 integrin cDNA construct, and three beta5 transfectant clones were selected for the expression of alphavbeta5 integrin at their cell surface. Despite a delayed entry in the exponential phase of growth, beta5-transfectant cells kept a proliferation ability similar to that of parental cells, while their growth rate was hindered in the presence of an anti-alphavbeta5 blocking antibody. Only simultaneous blockade of alphavbeta3 and alphavbeta5 by specific antibodies impeded the adhesion to vitronectin of beta5 transfectants and of the beta5-expressing cisplatin-resistant variant IGROV1-R10, suggesting that the two heterodimers cooperated in the regulation of this process. Cell surface expression of alphavbeta5 resulted in an attenuation of alphavbeta3-mediated migration on vitronectin. Alphavbeta5 participated to migration events in the absence of exogenous growth factors only in one transfectant clone and in IGROV1-R10 cells. Finally, the response to cisplatin was not significantly modified in beta5 transfectants when compared to IGROV1 parental cells.

Clinicopathological study of metallothionein immunohistochemical expression, in benign, borderline and malignant ovarian epithelial tumors.

Metallothioneins (MTs) are a family of cystein-rich metal-binding proteins, which are expressed in normal cells during fetal and postnatal life but also in a variety of human neoplasms. MT expression in human tumors has been linked to resistance to anticancer drugs and differentiation and progression in some types of tumors. This study examined the immunohistochemical expression of MTs in benign, borderline and malignant tumors of ovarian surface epithelium and the possible correlations with clinicopathological parameters and survival. A total of 87 cases with diagnosis of ovarian surface epithelial tumors were included. Specifically, 21 cases of benign cystadenomas (11 serous and 10 mucinous), 14 borderline (low malignant potential tumors, 8 mucinous and 6 serous) and 52 cases of ovarian cancer were analysed. Immunohistochemical expression of MT (cut-off level > 10% of tumor cells) was clearly associated with malignancy. A statistically significant correlation was found between the expression of MT in cancer cases and benign tumors (p < 0.0001) and cancer cases and borderline tumors p = 0.003. In cancer cases a difference was observed between grade I and III (p = 0.002). There was no correlation of MT overexpression with survival in the small number of ovarian carcinoma patients where it was analysed. MT constitutes a marker that characterizes aggressiveness and a high malignant potential in ovarian epithelial tumors. In diagnostic problems MT may help distinguish between benign, borderline and malignant tumors.