Papillary Serous Adenocarcinoma Research Articles

Tumorigenic potential of pituitary tumor transforming gene (PTTG) in vivoinvestigated using a transgenic mouse model, and effects of cross breeding with p53 (+/−) transgenic mice

BackgroundPituitary tumor-transforming gene (PTTG) is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis.MethodsTransgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals.ResultsPTTG transgenic offspring (TgPTTG) were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells. Tumorigenesis is a multi-step process, often requiring multiple oncogenes and/or inactivation of tumor suppressor genes. Therefore, to understand the contribution of p53 to PTTG induced tumorigenesis, we crossbred TgPTTG to p53+/− mice and maintained those 8 to 10 months. TgPTTG/p53+/− animals developed sarcomas faster than p53+/− alone as well as different tumor types in addition to cervical carcinomas in situ in 10 out of 17 females.ConclusionsWe conclude that while PTTG is a functional transforming oncogene, it requires an additional partner to effectively promote tumorigenesis through the loss of p53 include or between function or modulation.

Endometrial cancer diagnosed by Sister Mary Joseph nodule biopsy: Case report

A Sister Mary Joseph nodule is an umbilical metastasis found in less than 3% of patients with intra-abdominal or pelvic malignancy (Piura et al., 2006). These rare nodules have a wide range of presentations but most typically are noted to be a painful, ulcerated mass with serosanguineous to bloody discharge (Levine et al., 2010). Although rarely reported, the presence of a Sister Mary Joseph nodule can be an important diagnostic and prognostic factor in the assessment of gynecologic oncology patients. In this case we describe a patient who presented with a likely gynecologic malignancy and notable Sister Mary Joseph nodule. As an endometrial or cervical biopsy was difficult due to heavy vaginal bleeding, biopsy of the umbilical nodule allowed for an early tissue diagnosis of papillary serous adenocarcinoma and subsequently helped to guide staging and treatment options.

Metastatic Skin Lesions on Lower Extremities in a Patient with Recurrent Serous Papillary Ovarian Carcinoma: A Case Report and Literature Review

Clinical observation of skin metastasis in ovarian cancer cases is relatively uncommon. And distant metastatic skin lesions including the extremities are much rarer still as most metastatic skin lesions are located in the skin in the abdominal wall adjacent to where the primary ovarian tumors exist. We report the case of a 60-year-old woman who presented skin lesions on both lower extremities as a consequence of the metastasis of serous papillary adenocarcinoma of the ovary. She presented with erythematous and painful cutaneous nodules on both upper legs and in the inguinal area 42 months after initial diagnosis of ovarian cancer. Skin biopsy revealed metastasis of adenocarcinoma in the dermis. She was treated with surgical excision and systemic chemotherapy. Literature review has suggested that a combined modality approach including surgical excision and chemotherapy may be useful in the management of skin metastases due to ovarian cancer.

Identification of differentially expressed genes according to chemosensitivity in advanced ovarian serous adenocarcinomas: expression of GRIA2 predicts better survival

Background:The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours.Methods:To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas.Results:Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively).Conclusions:We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.

Serum KL-6 for diagnosis of ovarian carcinoma associated with dermatomyositis: two case reports and characteristic clinicopathological factors

Patients with dermatomyositis have a predisposition to the development of malignant tumors. The incidence of ovarian carcinoma, especially, is higher in patients with dermatomyositis than in the general population. Recently, it was reported that serum levels of KL-6 (Krebs von den Lungen-6) may be elevated in patients with dermatomyositis associated with ovarian carcinoma. Herein, we describe two cases of ovarian carcinoma associated with dermatomyositis. The first patient was a 46-year-old woman with stage Ib serous papillary adenocarcinoma of the ovary. At the time of diagnosis, she had a 13-year history of dermatomyositis, and an elevated serum KL-6 level. Reduction of the serum KL-6 level was noted after resection of the tumor. Immunohistochemistry revealed positive staining of the tumor for KL-6. The other case was a 58-year-old woman with stage IV ovarian carcinoma who also had a history of dermatomyositis. She was initially started on chemotherapy, which resulted in shrinkage of the tumor and reduction of the serum KL-6 level. Surgery was then performed for resection of the tumor, and the chemotherapy was continued. However, the patient died of cancer 1 year and 4 months after the start of the treatment. For patients with dermatomyositis and with elevation of the serum KL-6 level in the absence of severe interstitial pneumonia, associated ovarian malignancy should be ruled out.

Serous papillary adenocarcinoma probably arising from epithelial inclusions of the hepatic hilar lymph node

Only three cases of serous adenocarcinoma arising from Mullerian epithelial inclusions of the lymph node have been reported. Herein reported is a case of serous papillary adenocarcinoma arising probably from epithelial (Mullerian) inclusions of the hepatic hilar lymph node. A 73-year-old woman presented with peripheral neuropathy, which was thought to be a paraneoplastic syndrome associated with visceral malignancy. Total body examination, including X-P, US, CT, MRI, PET, and upper and lower gastrointestinal endoscopy was done. As the results, only lymph node swelling was detected in the hepatic hilus. Tumor was not identified in other sites. The physicians considered malignant lymphoma, and laparotomic excision of the hepatic hilar mass was performed. Cytological examination of abdominal cavity washing revealed no malignant cells. Grossly, the mass was firm and white and measured 4 × 5 × 5 cm. Microscopically, the mass showed carcinoma cells arranged in papillary and tubular patterns. The appearances strongly resembled serous papillary adenocarcinoma of the ovary. Lymph node structures were noted in some peripheral areas. No benign epithelial inclusions were recognized. Immunohistochemically, the carcinoma cells were positive for ER, PgR, CA125, WT1, p53. They were negative for TTF-1 and CDX-2. Because the positive ER, PgR, CA125, WT1, p53 and p16 are indicative of gynecologic malignancy, simple hysterectomy and bilateral salpingo-oophorectomy were performed, which showed no abnormalities. Cytological examination of abdominal cavity washing fluid revealed no malignant cells. The patient was treated by paclitaxel and carboplatin, and is now alive without metastasis 2 years after the first manifestation. The author reported a case of serous papillary adenocarcinoma arising probably from epithelial (Mullerian) inclusions of the hepatic hilar lymph node.

Can we safely omit paraaortic lymphadenectomy from the surgical staging of high-grade endometrioid, clear cell and papillary serous endometrial adenocarcinoma?

Can we safely omit paraaortic lymphadenectomy from the surgical staging of high-grade endometrioid, clear cell and papillary serous endometrial adenocarcinoma?

Salivary transcriptomic biomarkers for detection of ovarian cancer: For serous papillary adenocarcinoma

Ovarian cancer is the most lethal gynecological cancer due to lack of clear symptom and reliable screening biomarker in the early stage. The capability to detect the initiation of malignancy with a sensitive and effective approach is one of the most desirable goals for ovarian cancer therapy. In this study, we spearheaded noninvasive detection of ovarian cancer by salivary transcriptomic biomarkers, and evaluated the clinical utilities of discovered biomarkers using a clinical case–control study. To find salivary mRNA biomarkers, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled by Affymetrix HG-U133-Plus-2.0 array. The biomarker candidates selected from the microarray results were then subjected to clinical validation by RT-qPCR using an independent sample cohort including 21 ovarian cancer patients and 35 healthy controls. Seven downregulated mRNA biomarkers were validated. The logistic regression model revealed the combination of five validated biomarkers (AGPAT1, B2M, BASP2, IER3, and IL1B) can significantly discriminate ovarian cancer patients (n = 21) from the healthy controls (n = 35), yielding a receiver operating characteristic plot, area under the curve value of 0.909 with 85.7% sensitivity and 91.4% specificity. In summary, we have demonstrated that the RNA signatures in saliva could serve as biomarkers for detection of ovarian cancer with high sensitivity and specificity. This emerging approach with high-throughput, noninvasive, and effective advantages provides a feasible means for detection of systemic cancer, and opens a new avenue for early disease detection.

Delayed post-coital vaginal evisceration of intestines following interval debulking surgery

A 55-year-old Caucasian woman diagnosed with stage 3b serous papillary adenocarcinoma of the ovary was referred to a tertiary centre where she underwent neoadjuvant chemotherapy and interval debulk...

Identification of a Potential Ovarian Cancer Stem Cell Gene Expression Profile from Advanced Stage Papillary Serous Ovarian Cancer

Identification of gene expression profiles of cancer stem cells may have significant implications in the understanding of tumor biology and for the design of novel treatments targeted toward these cells. Here we report a potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma. Affymetrix U133 Plus 2.0 microarrays were used to interrogate the differentially expressed genes between side population (SP) and main population (MP), and the results were analyzed by paired T-test using BRB-ArrayTools. We identified 138 up-regulated and 302 down-regulated genes that were differentially expressed between all 10 SP/MP pairs. Microarray data was validated using qRT-PCR and17/19 (89.5%) genes showed robust correlations between microarray and qRT-PCR expression data. The Pathway Studio analysis identified several genes involved in cell survival, differentiation, proliferation, and apoptosis which are unique to SP cells and a mechanism for the activation of Notch signaling is identified. To validate these findings, we have identified and isolated SP cells enriched for cancer stem cells from human ovarian cancer cell lines. The SP populations were having a higher colony forming efficiency in comparison to its MP counterpart and also capable of sustained expansion and differentiation in to SP and MP phenotypes. 50,000 SP cells produced tumor in nude mice whereas the same number of MP cells failed to give any tumor at 8 weeks after injection. The SP cells demonstrated a dose dependent sensitivity to specific γ-secretase inhibitors implicating the role of Notch signaling pathway in SP cell survival. Further the generated SP gene list was found to be enriched in recurrent ovarian cancer tumors.

Diseminación inusual de un adenocarcinoma endometrial

Endometrial cancer is the fourth leading cause of cancer in women in developed countries, after breast, lung and colon cancer. The age of onset is usually at menopause and the main symptom is vaginal bleeding.The main predictors of lymph node involvement and metastasis are the depth of myometrial invasion and the degree of tumoral differentiation.Less than 5% of patients have stage IV cancer at diagnosis, and the initial presence of inguinal metastases is even more uncommon.We report the case of a 68-year woman with endometrial cancer who presented with vaginal bleeding and multiple inguinal tumors. Histological analysis of the uterus revealed a papillary serous adenocarcinoma with limited myometrial infiltration (less than 50%) and inguinal lymph nodes with poorly differentiated carcinoma, representing unusual progression of this type of cancer.

Pancreatic Metastasis of High-Grade Papillary Serous Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report

Introduction. Reports of epithelial ovarian carcinomas metastatic to the pancreas are very rare. We herein present a metastasis of high grade papillary serous ovarian cancer to mid portion of pancreas. Case. A 42-year-old patient was admitted with a non-specified malignant cystic lesion in midportion of pancreas. She had a history of surgical treatment for papillary serous ovarian adenocarcinoma. A cystic lesion was revealed by an abdominal computerized tomography (CT) performed in her follow up . It was considered as primary mid portion of pancreatic cancer and a distal pancreatectomy was performed. The final pathology showed high-grade papillary serous adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. Discussion. Metastatic pancreatic cancers should be considered in patients who present with a solitary pancreatic mass and had a previous non-pancreatic malignancy. Differential diagnosis of primary pancreatic neoplasm from metastatic malignancy may be very difficult. A biopsy for tissue confirmation is required to differentiate primary and secondary pancreatic tumors. Although, the value of surgical resection is poorly documented, resection may be considered in selected patients. Conclusion. Pancreatic metastasis of ovarian papillary serous adenocarcinoma has to be kept in mind when a patient with pancreatic mass has a history of ovarian malignancy.

Pathological implication and function of Bcl2-inhibitor of transcription in ovarian serous papillary adenocarcinomas

The Bit-1 protein appears to be a part of the integrin-specific signaling pathway involved into anoikis. When Bit1 is released from the mitochondria into the cytoplasm it can elicit caspase-independent apoptosis. The expression of Bit1 in 78 serous papillary adenocarcinomas and 78 normal epithelial ovarian tissue specimens was analyzed by immunohistochemistry. We also investigate Bit1 function by transfection. Bit1 was expressed in 100% and 33.3% of ovarian cancers and normal epithelial tissues, respectively, and its expression was significantly correlated with histologic grade and overall survival. However, Bit1 expression was not associated with age. We also confirmed that Bit1 overexpression in cytosol of Caov-3 cells induced apoptosis. Bit1 may be a useful pathological marker and a prognostic marker for serous papillary adenocarcinomas outcome. Its pro-apoptotic property also makes it a potential gene medicine for ovarian cancers therapy.

Gene regulatory network inference: evaluation and application to ovarian cancer allows the prioritization of drug targets

BackgroundAltered networks of gene regulation underlie many complex conditions, including cancer. Inferring gene regulatory networks from high-throughput microarray expression data is a fundamental but challenging task in computational systems biology and its translation to genomic medicine. Although diverse computational and statistical approaches have been brought to bear on the gene regulatory network inference problem, their relative strengths and disadvantages remain poorly understood, largely because comparative analyses usually consider only small subsets of methods, use only synthetic data, and/or fail to adopt a common measure of inference quality.MethodsWe report a comprehensive comparative evaluation of nine state-of-the art gene regulatory network inference methods encompassing the main algorithmic approaches (mutual information, correlation, partial correlation, random forests, support vector machines) using 38 simulated datasets and empirical serous papillary ovarian adenocarcinoma expression-microarray data. We then apply the best-performing method to infer normal and cancer networks. We assess the druggability of the proteins encoded by our predicted target genes using the CancerResource and PharmGKB webtools and databases.ResultsWe observe large differences in the accuracy with which these methods predict the underlying gene regulatory network depending on features of the data, network size, topology, experiment type, and parameter settings. Applying the best-performing method (the supervised method SIRENE) to the serous papillary ovarian adenocarcinoma dataset, we infer and rank regulatory interactions, some previously reported and others novel. For selected novel interactions we propose testable mechanistic models linking gene regulation to cancer. Using network analysis and visualization, we uncover cross-regulation of angiogenesis-specific genes through three key transcription factors in normal and cancer conditions. Druggabilty analysis of proteins encoded by the 10 highest-confidence target genes, and by 15 genes with differential regulation in normal and cancer conditions, reveals 75% to be potential drug targets.ConclusionsOur study represents a concrete application of gene regulatory network inference to ovarian cancer, demonstrating the complete cycle of computational systems biology research, from genome-scale data analysis via network inference, evaluation of methods, to the generation of novel testable hypotheses, their prioritization for experimental validation, and discovery of potential drug targets.

Complete biologic response to taxane based chemotherapy confirmed by [18F]FDG PET/CT and surgery in a cancer of unknown primary site

Cancers of an unknown primary site are heterogenous with respect to their clinical and pathologic features. They are generally very aggressive, but specific favorable subsets have a better prognosis. For these favorable subsets, taxane based chemotherapy is very effective for a subset of woman with papillary serous peritoneal adenocarcinoma. A 52 year-old woman underwent [18F]-FDG PET/CT for routine health screening. On PET/CT, multiple hypermetabolic lymph nodes were detected in the paraaortic spaces, and there were no other hypermetabolic abnormalities. The patient was diagnosed with an unknown primary cancer that probably originated from the ovary or peritoneum, according to clinical studies and biopsy results. This was not a typical case of a favorable subset of cancer of an unknown primary site, but the tumor showed complete biologic response to taxane based chemotherapy as revealed by PET/CT, and necrotic tumor cells were confirmed by surgery.

Case report of undifferentiated embryonal sarcoma of a liver misdiagnosed with fallopian tube carinoma metastasis

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare but aggressive primary tumor of the liver occurring most frequently in childhood. Its frequency in the adult population is extremely low. A 41-year-old Korean woman, who had previously undergone treatment for fallopian tube serous papillary adenocarcinoma, presented with a growing solitary mass in the right liver lobe after treatment. Although CA-125 level was normal, the mass was initially presumed to be metastasis from the primary fallopian tube carcinoma. On further examination, it was shown to be a UESL. Primary liver tumors should be considered in differential diagnoses in patients with fallopian tube cancer who subsequently raised liver tumors. This is particularly important when there is no direct evidence of recurrence of fallopian tube cancer.

Multiple Gastric Metastases from Ovarian Carcinoma Diagnosed by Endoscopic Ultrasound with Fine Needle Aspiration

Metastasis to the stomach from nongastric tumors is a rare event. We present a case of ovarian cancer metastasis to the gastric wall that presented as multiple subepithelial gastric lesions. A 55-year-old female with known stage III b serous ovarian cancer was admitted to the hospital with melena and anemia. A 1.5 to 2 cm subepithelial mass with superficial overlying erosion in the antrum was seen in Esophagogastroduodenoscopy (EGD). Initial endoscopic mucosal biopsies were normal. An Endoscopic Ultrasound (EUS) was performed, which revealed two subepithelial lesions with the typical appearance of a gastrointestinal stromal tumor. Fine needle aspiration (FNA) of both masses revealed papillary adenocarcinoma from an ovarian papillary serous adenocarcinoma. This is the first reported case of multiple gastric metastatic lesions from ovarian cancer diagnosed by EUS FNA.

F-18 Fluoride Uptake in Calcified Extraosseous Metastases From Ovarian Papillary Serous Adenocarcinoma

F-18 Fluoride Uptake in Calcified Extraosseous Metastases From Ovarian Papillary Serous Adenocarcinoma

Endometrioid Adenocarcinoma with High-Grade Transformation with Serous and Choriocarcinomatous Differentiation - A Case Report

A choriocarcinoma component with a malignant tumor is relatively rare. We present a case of an 85-year-old woman with mixed carcinoma, which was endometrioid adenocarcinoma with squamous differentiation, choriocarcinoma and a disseminated peritoneal nodule, which was papillary serous adenocarcinoma. The patient received surgery and conservative treatment. Twenty weeks after surgery, a recurring tumor appeared at the Douglas pouch. Histology showed that the recurring tumor was poorly differentiated carcinoma that was very different from the primary tumor. This case represents an unusual uterine corpus cancer with high-grade transformation with serous and choriocarcinomatous differentiation. This case also demonstrates the capacity of tumor cells to differentiate into divergent elements.

Salivary transcriptomic biomarkers for detection of ovarian cancer: for serous papillary adenocarcinoma

Ovarian cancer is the most lethal gynecological cancer due to lack of clear symptom and reliable screening biomarker in the early stage. The capability to detect the initiation of malignancy with a sensitive and effective approach is one of the most desirable goals for ovarian cancer therapy. In this study, we spearheaded noninvasive detection of ovarian cancer by salivary transcriptomic biomarkers, and evaluated the clinical utilities of discovered biomarkers using a clinical case-control study. To find salivary mRNA biomarkers, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled by Affymetrix HG-U133-Plus-2.0 array. The biomarker candidates selected from the microarray results were then subjected to clinical validation by RT-qPCR using an independent sample cohort including 21 ovarian cancer patients and 35 healthy controls. Seven downregulated mRNA biomarkers were validated. The logistic regression model revealed the combination of five validated biomarkers (AGPAT1, B2M, BASP2, IER3, and IL1B) can significantly discriminate ovarian cancer patients (n = 21) from the healthy controls (n = 35), yielding a receiver operating characteristic plot, area under the curve value of 0.909 with 85.7% sensitivity and 91.4% specificity. In summary, we have demonstrated that the RNA signatures in saliva could serve as biomarkers for detection of ovarian cancer with high sensitivity and specificity. This emerging approach with high-throughput, noninvasive, and effective advantages provides a feasible means for detection of systemic cancer, and opens a new avenue for early disease detection.