Ovarian Mucinous Adenocarcinoma Research Articles

Cistoadenocarcinoma de ovario y apéndice

Mucinous cystic adenocarcinoma of the ovary and appendix We report a 73 years old woman presenting with a right ovarian tumor. Preoperative carcinoembryonic antigen and CA-125 levels were above normal levels. The patient was operated, performing a bilateral oopho- rectomy an appendectomy. The pathological study of the surgical piece reported a mucinous ovarian cystic adenocarcinoma that infi ltrated the wall but did not reach the capsule. A mucinous cystadenoma was found in the contralateral ovary. A mucinous adenocarcinoma was detected in the appendix, involving the wall but sparing the serosa. The patient was subjected to chemotherapy and six months after the fi rst operation a tumor relapse was detected. A new excision was carried out and the patient continues with adjuvant chemotherapy. The ovarian an appendiceal tumors could be synchronic or a primary and secondary localization.

Mucinous adenocarcinoma developed from human fallopian tube epithelial cells through defined genetic modifications

Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbriated end of the distal fallopian tube. To test this hypothesis, we immortalized a normal human fallopian tube epithelial (FTE) cell line by using retrovirus-mediated overexpression of the early region of the SV40 T/t antigens and the human telomerase reverse transcriptase subunit (hTERT). These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRASV12. Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence growth assay and inoculation into nude mice via subcutaneous and intraperitoneal injection. As expected, the HRASV12-transformed FTEs produced tumors through both subcutaneous and intraperitoneal injections, whereas no tumor growth was observed in immortalized FTEs. Unexpectedly, histopathological examination of tumors resulting from subcutaneous as well as intraperitoneal injections revealed largely poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma. The tumor implants invaded extensively to the liver, colon, spleen, omentum, adrenal gland and renal capsule. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and Müllerian lineage marker PAX8. Our study demonstrates that FTEs can generate poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma through genetic modifications. Thus, we provide the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma.

Abstract 4246: Long-term primary culture of a mucinous ovarian adenocarcinoma containing CD133 positive cells

Abstract Among epithelial ovarian cancers, mucinous ovarian cancer (MOC) is rare but highly lethal. In this work, we describe the successful long-term primary culture of a heterogeneous population of cells derived from a tumor biopsy obtained from a 50 yr old patient diagnosed with stage IIIc ovarian cancer that underwent debulking surgery. The tumor was hemorrhagic and pathologically classified as a MOC. To understand the biological behavior in culture of this rare tumor type, the tissue biopsy was enzymatically digested, and the bulk of the cells were allowed to attach to regular tissue culture flasks. After 24 h in culture, the cells that adhered to the plate formed colonies of epithelial appearance. Such colonies were however surrounded by cells with mesenchymal phenotype. We considered the latter cells as part of the tumor microenvironment, and, consequently did not intend to separate them from the epithelial cells-a method that has been traditionally used to generate epithelial cancer cell lines. After two months of incubation and with periodic media changes, the culture still displayed a combination of epithelial-mesenchymal phenotype. When we compared the phenotype observed in photographs taken four days after initial plating versus those taken two months later, it was clear the net growth of the epithelial, but not the mesenchymal component of the culture. The growth of the epithelial component was confirmed by BrdUrd incorporation. Of notice, each epithelial foci was always closely surrounded by mesenchymal-like cells; when the mesenchymal component of the culture was removed to enrich the epithelial cell population, the epithelial cells stopped growing and underwent quiescence. In the mixed culture, the cells with epithelial morphology stained mostly positive for E-cadherin and negative for vimentin, whereas the opposite occurred for the cells with mesenchymal morphology. Curiously, some cells in the periphery of the epithelial compartment where positive for the mesenchymal marker vimentin, suggesting the existence of a “transitional” epithelial-mesenchymal phenotype. We studied the expression of the stem cell marker CD133 and of the endothelial marker CD31. We found CD133 positive cells in both epithelial and mesenchymal compartments, whereas CD31 positive cells were only found in the mesenchymal area. In conclusion, this study demonstrates that it is feasible to maintain in culture, for a relatively long period of time, a complex mixture of cells obtained from a primary MOC. We show that it is the complexity of the cellular components what allows the culture to grow, confirming in vitro the importance of the tumor microenvironment for the successful proliferation of the ovarian epithelial cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4246. doi:1538-7445.AM2012-4246

A case of ovarian mucinous adenocarcinoma in a premenarcheal girl

We report a case of a 12-year-old premenarcheal girl who developed ovarian mucinous adenocarcinoma. The tumor, which originated from the right ovary, weighed 1400 g, and had a smooth surface and thin capsule, was extirpated. The cut surface showed multilocular cysts of various sizes and yellowish gelatinous to solid parts that accounted for approximately 40% of the cut surface. The histological findings showed a continuous mixture of mucinous adenoma, mucinous borderline tumor, and mucinous adenocarcinoma with an expansile invasive pattern. It was assumed that an ovarian mass developed in an early period after birth or infancy, and the mutation of certain oncogens occurred in an early period, leading to cancer. While some etiological hypotheses concerning ovarian carcinogenesis have been suggested, we believe this case provides valuable information when considering a new onset mechanism of ovarian epithelial malignant tumors.

Prognostic Significance of Stromal Microinvasion in the Intestinal Type of Ovarian Mucinous Adenocarcinoma

The purpose of this study was to assess clinical outcomes with respect to the extent of stromal invasion in patients with stage I ovarian mucinous adenocarcinoma (MAC) of the intestinal type. We retrospectively reviewed the medical records and pathologic slides of 113 patients with stage I ovarian MACs who were treated at the Asan Medical Center from January 1994 to July 2009. According to the recent histopathologic criteria, MACs were classified into 3 groups: intraepithelial carcinoma without invasion (IEC), intraepithelial carcinoma with microinvasion (IECMI), and mucinous adenocarcinoma with extensive invasion (MACEI). Stromal invasion was confined to the tumors showing severe cytologic atypia in the invasive foci. Therefore, cases showing mucin granulomas composed only of macrophages without malignant cells were excluded from the definition of invasion. Of the 113 patients, 54 (47.8%) had IEC, 15 (13.3%) had IECMI, and 44 (38.9%) had MACEI. There were no differences among groups in age, menopausal status, CA-125 level, surgical procedures, stage, capsular and lymphovascular space invasion. The 5-year disease-free-survival rates in the IEC, IECMI, and MACEI groups were 97.7%, 77.3%, and 79.9%, respectively (IEC vs IECMI, P=0.004; IEC vs MACEI, P=0.012; IECMI vs MACEI, P=0.555). Prognosis was significantly poorer for patients with IECMI than for those with IEC, but not different between patients with IECMI and MACEI. Stromal microinvasion in ovarian MAC is a significant prognostic factor. Therefore, diligent search for "stromal microinvasion" with adequate sampling of tumor tissue are important at the time of histopathologic diagnosis, and patients with IECMI should no longer be treated identically to those with IEC.

Abstract 1602: Mucinous adenocarcinoma developed from human fallopian tube epithelial cells through a combination of defined genetic modifications and tumor microenvironment

Abstract Epithelial ovarian cancer includes several distinct histologic types including serous, mucinous, endometrioid, and clear cell. The cell origin of these distinct epithelial ovarian cancers has been debated for many years. Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbrial end of distal fallopian tube, although direct experimental evidence supporting this hypothesis is still lacking. To test this hypothesis, we immortalized a normal human fallopian tubal epithelial (FTE) cell line by using a retrovirus-mediated infection expressing the early region of SV40 T/t antigen and the human telomerase reverse transcriptase. These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRASV12. Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence assay and inoculation into nude mice via subcutaneous or intraperitoneal injections. As expected, the HRASV12-transformed FTEs produced tumors through both subcutaneous and intraperitoneal injections, while no tumor growth was observed in immortalized FTEs. To our surprise, however, while histopathologic examination of resulting tumor from subcutaneous injections revealed a largely undifferentiated carcinoma with focal mucin production, tumors from intraperitoneal injections showed mucinous adenocarcinoma with rich mucin production from an undifferentiated area. The mucinous differentiation of tumors was most prominent near the peritoneal fat and other peritoneal organs including the pancreas, spleen, and intestine. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and CA125. Our study demonstrates that FTEs can generate mucinous adenocarcinoma through genetic modifications and that such mucinous differentiation is dependent on the peritoneal microenvironment. Thus, the experiment described here provided the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma, a distinct histologic entity of epithelial ovarian cancers whose origin is largely unknown. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1602. doi:10.1158/1538-7445.AM2011-1602

Late presentation of a mucinous ovarian adenocarcinoma which was initially diagnosed as a primary pancreatic carcinoma: a case report and review of the literature

IntroductionAdenocarcinoma of the ovary is an aggressive neoplasm which often metastasizes to the lung or liver. Metastases rarely occur to the pancreas, but a tissue diagnosis is required to confirm this event. Although most tumors of the pancreas are primary pancreatic neoplasms, metastatic lesions have been reported most commonly as arising from renal cell carcinoma.Case presentationWe report the case of a 51-year-old Caucasian woman with ovarian mucinous adenocarcinoma with metastasis to the head of the pancreas that was originally misdiagnosed as a pancreatic primary tumor.ConclusionMucinous ovarian adenocarcinomas rarely metastasize to the pancreas. New pancreatic lesions should be investigated through tissue biopsy and tumor markers, while keeping an open-minded differential diagnosis to avoid a misdiagnosis or a delay in treatment.

Efficacy of a methyl ester of 5-aminolevulinic acid in photodynamic therapy for ovarian cancers

Photodynamic therapy (PDT) is a new approach to cancer treatment that utilizes photochemical reactions induced by a combination of an oncophilic photosensitizing agent and laser light. With an aim to apply PDT for intraperitoneal disseminated foci of advanced or recurrent ovarian cancers, the present study was conducted to evaluate the antitumor effect of PDT using a methyl ester of 5-aminolevulinic acid (Methyl-ALA) on various types of human ovarian cancer in a subcutaneous xenograft model in nude mice and to elucidate the mechanism of its antitumor effect. HTOA, MCAS, and TOV21G cell lines derived from human ovarian serous, mucinous, and clear cell adenocarcinoma, respectively, were used in this study. The mice in the treatment group and in the control group received an intraperitoneal injection of 250 mg/kg of Methyl-ALA and PBS alone, respectively. PDT was administered by 10 min irradiation using a 150 W halogen light, 3 h after Methyl-ALA or PBS injection. Each mouse received PDT twice a week for 3 weeks. Methyl-ALA-PDT significantly suppressed the growth of HTOA tumors as compared to control, whereas there was no significant effect on the growth of MCAS or TOV21G tumors. Methyl-ALA-PDT significantly increased apoptosis in implanted HTOA tumors as well as cultured cells. Western blot analysis showed that amount of expression of milk fat globule-EGF-factor 8, which binds to apoptotic cells and thereby facilitates their phagocytosis, significantly increased in HTOA tumors receiving Methyl-ALA-PDT, compared with untreated HTOA tumors. In addition, reduced vascular endothelial growth factor and CD34-positive microvessel density were found in solid HTOA tumors treated by Methyl-ALA-PDT, suggesting that the antitumor effect of Methyl-ALA-PDT is due to induction of apoptosis and reduction of angiogenesis. In comparison with HTOA cells, HPLC analysis demonstrated a significantly smaller intracellular amount of protoporphyrin IX (PpIX) in MCAS and TOV21G cells. PpIX is readily converted from Methyl-ALA and elicts photocytotoxicity. We conclude that Methyl-ALA-PDT could be an effective treatment in ovarian cancer and should be tested to apply intraperitoneally disseminated micro-foci during surgery.

The discrimination between primary mucinous and metastatic ovarian adenocarcinoma ;

The discrimination between primary mucinous and metastatic ovarian adenocarcinoma ;

Treatment results of the ovarian mucinous adenocarcinoma in our hospital

Treatment results of the ovarian mucinous adenocarcinoma in our hospital

Treatment outcome of ovarian mucinous adenocarcinoma in our hospital with speculation about lymphadenectomy

Treatment outcome of ovarian mucinous adenocarcinoma in our hospital with speculation about lymphadenectomy

Clinical review of ovarian mucinous adenocarcinoma

Clinical review of ovarian mucinous adenocarcinoma

CK7, CK20, CDX2 and MUC2 Immunohistochemical Staining Used To Distinguish Metastatic Colorectal Carcinoma Involving Ovary from Primary Ovarian Mucinous Adenocarcinoma

Colorectal adenocarcinoma, the most common tumor that metastasizes to the ovary, is often difficult to distinguish from primary ovarian mucinous adenocarcinoma (POMA). Obtaining the correct diagnosis is difficult but crucial to treatment and prognosis. We evaluated the immunohistochemical (IHC) expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), CDX2, CEA, MUC2, MUC5AC and alpha-methylacyl-CoA racemase (AMACR) in 22 POMAs and 41 metastatic colorectal adenocarcinomas (MCAOs) involving ovaries. MCAOs, in contrast with POMAs, were almost always negative for MUC5 (97.6%), often negative for CK7 (82.9%), focal or diffuse positive for CDX2 (73.2%), diffuse positive for CK20 (65.9%), focal or diffuse positive for MUC2 (51.2%), diffuse positive for CEA (41.5%) and negative for AMACR (41.5%). We therefore considered CK7 (-), CK20 (diffuse +), CDX2 (+) and MUC2 (+) to be colonic markers and regarded cases with expression of more than two colonic markers as MCAO, those with no expression of colonic markers as POMA and those with expression of one colonic marker as indeterminate. Using CK7/CK20/CDX2/MUC2, 82.5% of the cases were correctly classified, 6.3% were misclassified and 6.3% were indeterminate. CK7, CK20, CDX2 and MUC2 IHC staining is a useful adjunctive diagnostic tool to differentiate MCAOs from POMAs, in addition to clinical history and gross and microscopic findings.

Recurrent Urachal Mucinous Adenocarcinoma Presenting as Bilateral Ovarian Tumors on Cesarean Delivery

Secondary ovarian cancers, Krukenberg tumors, are a distinctive subset of metastatic tumors arising from the gastrointestinal tract (stomach, colon, and appendix), the biliary system, the breast, or other genital organs. These tumors account for 5% of all ovarian malignancies. Such metastases could mimic primary mucinous ovarian adenocarcinomas. Metastases from the urinary tract are uncommon. Primary adenocarcinoma of the bladder accounts for less than 1% of all bladder malignancies; one third of these tumors are urachal in origin. Urachal cancers are rare and tend to occur in older men (mean age, 50-60 years); however, it was described previously in a 15-year-old girl. Symptoms include hematuria, dysuria, frequency, urgency, and recurrent urinary tract infections. These tumors have a predilection to locally spread to the surrounding organs. Ovarian metastasis is a rare event and is infrequently reported in literature.

High expression of N-acetylglucosaminyltransferase V in mucinous tumors of the ovary

N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine (GlcNAc) on asparagine-linked oligosaccharides of cell proteins. The present study aimed to investigate GnT-V expression and its prognostic significance in epithelial ovarian cancer. GnT-V expression was studied by immunohistochemistry in 83 surgically resected ovarian cancers, and the staining intensity was evaluated. High GnT-V expression in cancer cells was found in 17 (20.5%) of the 83 cases, and was positively correlated with early FIGO staging. In the histological type, mucinous adenocarcinoma showed significantly strong immunostaining compared to the non-mucinous type (P<0.001). In 36 mucinous tumors, the GnT-V immunostaining score was significantly higher in cancer than in benign and borderline tumors (P<0.001). NOM-1, a human ovarian mucinous adenocarcinoma cell line, expressed strong GnT-V protein and swainsonine treatment suppressed beta1-6GlcNAc branching and reduced migration ability significantly (P<0.001). These results suggested that GnT-V might be involved in the malignant potential of mucinous ovarian cancer.

Mixed ovarian large cell neuroendocrine carcinoma, mucinous adenocarcinoma, and teratoma: A report of two cases and review of the literature

Large cell neuroendocrine carcinoma of the ovary is a rare recently established entity. Few cases have been reported in the literature, and they are usually associated with another type of surface epithelial tumor. The association of a large cell neuroendocrine carcinoma with a surface epithelial tumor and a teratoma is even rarer, with only two cases previously described. We report the cases of two patients in their fifties who presented with a growing abdominal mass and died of metastatic disease within less than a year. Histological assessment revealed large cell neuroendocrine carcinoma admixed with mucinous adenocarcinoma and teratoma. Different hypotheses regarding the origin of large cell neuroendocrine carcinoma of the ovary are discussed. The immunohistochemical pattern of staining for cytokeratin 7 and cytokeratin 20 suggests that the composite epithelial tumors originated from the pre-existing teratoma.

The expression of six biomarkers in the four most common ovarian cancers: correlation with clinicopathological parameters

This study aimed to evaluate the relationship of fascin-1, matrix metalloproteinase (MMP)-2, MMP-9, cortactin, survivin, and epidermal growth factor receptor (EGFR) expression with clinicopathological parameters for the four most common ovarian surface epithelial carcinomas. Six biomarkers were investigated immunohistochemically using tissue microarrays of 185 specimens including 79 serous cystadenocarcinomas, 47 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas, and 14 clear cell carcinomas. The four most common ovarian carcinomas showed significant expression of fascin-1, cortactin, survivin, and EGFR, but not of MMP-2 and MMP-9. In addition, higher immunostaining scores for fascin-1 in mucinous cystadenocarcinomas correlated with T stage, N stage, American Joint Committee on Cancer AJCC clinical stage, and a poorer survival rate; for cortactin in serous cystadenocarcinomas correlated with T stage; for cortactin in clear cell carcinomas correlated with T and clinical AJCC stages; and for survivin in clear cell carcinomas correlated with T stage and AJCC clinical stage. In addition, higher immunostaining scores for fascin-1, cortactin, and survivin correlated with poorer tumor differentiation in serous, mucinous, and endometrioid adenocarcinomas. Thus, the expression of fascin-1, cortactin, and survivin may be helpful in evaluating the aggressiveness of ovarian mucinous, serous, and clear cell adenocarcinoma. Additionally, the expression of fascin-1 may be an independent prognostic risk factor in mucinous cystadenocarcinoma.

Combination chemotherapy of oxaliplatin and 5‐fluorouracil may be an effective regimen for mucinous adenocarcinoma of the ovary: A potential treatment strategy

Resistance of ovarian mucinous adenocarcinoma to standard chemotherapy with paclitaxel and carboplatin is associated with poor prognosis, and an effective treatment is needed. The present study aimed to identify an effective chemotherapy for ovarian mucinous adenocarcinoma. Five human ovarian mucinous adenocarcinoma cell lines (MN-1, OMC-1, RMUG-L, RMUG-S, TU-OM-1) were used in this study. Sensitivity of the cells to the anticancer agents was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and we assessed drug sensitivity by calculating the assay area under the curve for each agent. Protein expression was confirmed by Western blot analysis. We also examined the efficacy of combination chemotherapy on survival in a xenograft model of nude mice. The IC(50) to anticancer agents ranged widely. The assay area under the curve indicated that two of five cell lines (MN-1, TU-OM-1) were sensitive to oxaliplatin, 5-fluorouracil and etoposide, and only one (TU-OM-1) was sensitive to 7-ethyl-10-hydroxycamptothecin, which is an active metabolite of camptothecin. All cell lines were resistant to cisplatin and paclitaxel. The combination of oxaliplatin and 5-fluorouracil resulted in additive or synergistic effects on all cell lines. The combination of oxaliplatin and 5-fluorouracil significantly prolonged survival in a ovarian mucinous adenocarcinoma xenograft model of nude mice. Protein expression levels of the excision repair cross-complementation group 1 were lower in oxaliplatin sensitive cell lines. Exposure to 5-fluorouracil down-regulated cross-complementation group 1 expression in ovarian mucinous adenocarcinoma cells. We conclude that combination chemotherapy consisting of oxaliplatin and 5-fluorouracil was an effective treatment for ovarian mucinous adenocarcinoma and may be a pivotal candidate for a novel treatment strategy.

N-Acetylglucosamine 6-O-sulfotransferase-2 as a tumor marker for uterine cervical and corpus cancer

N-Acetylglucosamine 6-O-sulfotransferase-2 (GlcNAc6ST2) is ectopically expressed in ovarian mucinous and clear cell adenocarcinoma [Kanoh et al., Glycoconj J 23:453-460, 2006]. Here we studied whether GlcNAc6ST2 protein can be detected in sera from patients with gynecological cancers and could serve as a tumor marker. First, we created a monoclonal antibody and polyclonal antiserum against GlcNAc6ST2. These antibodies were specific for GlcNAc6ST2, as shown by Western blot analysis and immunoprecipitation. Using these antibodies, we constructed a sandwich ELISA method for detecting GlcNAc6ST2 in the serum. GlcNAc6ST2 provided lower positive rates for ovarian cancer than CA125, but higher positive rates for uterine cervical and corpus cancer than SCC antigens and CA125, respectively. A significantly higher percentage of stage I uterine cervical and corpus cancers were positive for GlcNAc6ST2 than for SCC antigens and CA125, respectively. GlcNAc6ST2 could therefore be a good serological marker for detecting early-stage uterine cervical and corpus cancers.

Expression of hepatocyte nuclear factor 4α in primary ovarian mucinous tumors

Hepatocyte nuclear factor 4 alpha (HNF4 alpha) is a member of the nuclear receptor superfamily and is expressed in several endodermal tissues. The aim of the present study was to examine the expression of HNF4 alpha on ovarian epithelial tumors with immunocytochemistry and immunohistochemistry using mAbs recognizing P1 and P2 promoter-driven HNF4 alpha. Ovarian mucinous adenoma, mucinous tumors of borderline malignancy, and mucinous adenocarcinoma had positive nuclear staining for HNF4 alpha (41/45, 91%). One-third (34%) of mucinous tumors had P1-positive staining and most had P1/P2-positive staining (93%). MUC2- and MUC5AC-positive staining was observed in 34% and 95% of mucinous tumors, respectively. The histological subtype of these mucinous tumors was not correlated with HNF4 alpha expression. On cytology it was found that cancer cells in the ascites from ovarian mucinous adenocarcinomas were HNF4 alpha positive, but tumor cells in ascites from other types of ovarian carcinomas were negative for HNF4 alpha. Thus, HNF4 alpha is demonstrated to be a useful marker for histological and cytological diagnosis of ovarian mucinous tumors.