Surface Epithelial Carcinomas Research Articles

FREQUENCY OF P53 EXPRESSION IN EPITHELIAL OVARIAN CANCER

Background: The ovarian carcinomas are the most cause of death in women due to cancer. The most common and lethal gynecological malignancy is malignant epithelial tumor.p53 may be used as a marker to predict aggressive behavior and poor response to standard chemotherapy.
 Objective: To observe the frequency of positive immunohistochemical expression of p53 in surface epithelial carcinoma.
 Materials and methods: A cross-sectional study for immunohistochemical expression of p53 on 100 diagnosed cases of surface epithelial carcinoma was conducted in the department of Histopathology, Chughtai Institute of of Pathology, Lahore during a period of 6 months. Nuclear staining for p53 was considered as positive. Cases with more than 10% positivity in tumor cells were considered as positive.
 Results: The mean age of patients and size of tumor were 48.70 ± 10.5 1 years and 9.83 ± 5.33 cm respectively. 25% (n=25) patients had low histologic grades while 75%(n=75) patients had high histological grades.47% (n=47)patients were p53 positive and 53% (n=53) patients were negative for immunohistochemical expression of p53.
 Conclusion: The present study states p53 positivity in 47% cases of epithelial ovarian cancer and the data fits to the proposed dualistic pathway of ovarian carcinogenesis as expression of p53 positive cases in high grade cancers is statistically significant ( <0.05).

Role of podoplanin, E-cadherin, Ki-67 in the dissemination of tumor cells in ovarian surface epithelial carcinoma-An immunohistochemical study

Background/aimTo understand the biological behaviour, ovarian carcinoma should be approached as a complex tissue composed of tumor cells, ECM proteins, endothelial cells, fibroblasts, inflammatory cells and lymphatics. We aimed to investigate the role of proliferation index of the tumor cells, cell adheshion molecules and lymphangiogenesis in the dissemination of tumor in ovarian surface epithelial carcinomas using suitable antibodies. Materials and methodsFifty-nine cases of ovarian carcinoma were assessed immunohistochemically to quantify the intratumoral and peritumoral LVD, podoplanin expression in stroma, E-cadherin expression and proliferation index of the tumor cells. Descriptive statistics were done stratifying the cases into early stage(FIGO-I) and advanced stage (FIGO-II,III,IV).Receiver operating curve was applied to determine the cut off of intratumoral LVD, peritumoral LVD, Ki-67 to discriminate early stage and advanced stage disease and the cut offs were validated by generating regression model. ResultsIntratumoral LVD (p = 0.001), peritumoral LVD (p = 0.000), high Ki-67 (p = 0.000), podoplanin expressing cancer associated fibroblasts (p = 0.002) and macrophages expressing podoplanin (p = 0.003) were significantly associated with advanced stage disease. Intratumoral LVD, peritumoral LVD and Ki67 at cut offs of 3.5, 9.5 and 30 % emerged as discriminators of early stage disease from advanced stage disease by ROC curve analysis. Peritumoral LVD > 9.5 had the highest odds of advanced disease (OR-33.948, CI-4.631-38.622). ConclusionOSECs with intratumoral LVD > 3.5, peritumoral LVD > 9.5 and Ki-67 > 30 % should be considered for aggressive chemotherapy and frequent follow-up. Peritumoral LVD and podoplanin expression in components of tumor stroma have a determinant role in tumor dissemination in OSEC.

A Study of Expression and Significance of p53 in Malignant Ovarian Surface Epithelial Tumours

To assess the immunohistochemical patterns of p53 in malignant surface epithelial tumours of ovary and correlate it with clinico-pathological parameters. Forty cases of histopathologically proven surface epithelial carcinomas of the ovary were studied. Immunohistochemistry was done and expression of p53 was analysed and these findings were correlated with clinico-pathological parameters. p53 expression was found in 55% of malignant surface epithelial tumours of ovary. There was significant association of p53 expression with histological grade (p = 0.034) and omental deposits (p = 0.005). p53 expression was associated with higher grade and omental deposits. Routine analysis of this gene could have profound implications on prognosis and could open new avenues for management.

Clinicopathological Spectrum of Surface Epithelial Ovarian Carcinoma and its Association with Serum CA-125 Levels: A Cohort Study

Introduction: The ovaries are the primary female reproductive organs and endocrine glands. Ovarian carcinoma has often been called as the silent killer because the symptoms may develop so late that the chances of cure are very poor. According to World Health Organisation (WHO) ovarian tumours are classified based upon their most probable tissue of origin: surface epithelial (65%), germ cell (15%), sex cord-stromal (10%), metastases (5%) and miscellaneous. The malignant surface epithelial tumours are further classified by cell type into serous, mucinous, endometrioid, clear cell, brenner, seromucinous and undifferentiated carcinoma. The most widely used tumour marker in ovarian carcinoma is CA-125 which is considered as gold standard. Aim : To find the utility of serum CA-125 levels in histopathological variants of malignant surface epithelial tumours, degree of differentiation and their distribution according to clinical data pertaining to age, parity, history of use of oral contraceptive pills/ovulation inducing drugs and family history of carcinoma ovary/breast or colon. Materials and Methods: A prospective study (cohort study) was done at Guru Gobind Singh Medical College and Hospital, Faridkot over a period of 1.5 year (April 2017-oct 2018) on 50 ovarian masses which were diagnosed as ovarian carcinoma. Data was represented as frequencies and percentages for categorical variables and as means and standard deviations for continuous variables. Analysis was done using Statistical Package for Social Sciences (SPSS) v 20.0.0. Results: Serous carcinoma (80%) topped among all the histological variants. Serous high grade carcinoma was more common than serous low grade carcinoma. Maximum rise of serum CA-125 levels were seen in serous carcinoma. Among serous carcinomas, mean serum CA-125 levels were more in high grade serous carcinoma than low grade serous carcinoma and the results were statistically significant. conclusion: Serum CA-125 level is a great tool for diagnosis, follow-up and prognosis of ovarian carcinomas.

Abstract 5292: Glycogen synthase kinase-3 beta (GSK-3b) genomic alterations and increased programmed death-ligand 1 (PD-L1) expression in advanced malignancies

Abstract Background: GSK-3β, a serine/threonine kinase, has been implicated in the pathogenesis of many cancers. Aberrant expression of GSK-3β promotes tumor growth and chemotherapy resistance. GSK-3β phosphorylates target pro-oncogenes (C-Jun and C-myc), as well as non-glycosylated forms of PD-L1 leading to its proteasome degradation (Li CW Nat Commun 2016). GSK-3β tumor genomic alterations have been described, yet are not well-characterized. Characterizing alterations and functional impact can guide patient selection for treatment with GSK-3β inhibitors and related combinations in clinical development, including 9-ING-41, a first-in-class, selective small molecule GSK-3β inhibitor currently in phase 1/2 clinical trial (NCT03678883). Methods: Publicly-available tumor genomic data from cBioPortal was curated and analyzed. For each tumor with a GSK-3β alteration, histology and GSK-3β protein change/copy number variation (CNV) were obtained. A second cohort of tumors obtained from Caris Life Sciences (n=73,324) was interrogated for GSK-3β genomic alterations and PD-L1 expression (assessed via SP-142 antibody on tumor cells, cutoff used was 5%). Chi-square test was used to assess significance between PD-L1 expression of GSK3β-mutated tumors and that of GSK3β-wild type (wt) tumors. Results: Of 46,237 cBioPortal tumors, 430 (1%) tumors had a GSK3β mutation or CNV. Similarly, of 73,324 samples from Caris, 819 (1%) tumors had GSK3β mutations. When combining the data from both cohorts, the histologies with most frequent GSK3β mutations were uterine endometrioid carcinoma (4%), non-melanoma skin cancer (3%), uterine neoplasms (3%), and melanoma (2%). Overall, top protein changes included R396Q (n=44), H310Q (n=40), R418C (n=16), and S215L (n=15). Of the top mutated loci, R96 (n=14) and R180 (n=12) are located in a key binding pocket for phosphoprotein GSK3β substrates. The association between PD-L1 expression and GSK3β mutations was evaluated in 55,138 cases. The frequency of PD-L1 expression was significantly higher among GSK3β-mutated tumors compared to wt in colorectal cancer (8% vs. 4%, p=0.02), endometrial cancer (11% vs. 7%, p=0.05), melanoma (42% vs. 23%, p=0.01), ovarian surface epithelial carcinoma (20% vs. 7%, p=0.001), and uterine sarcoma (40% vs. 8%, p=0.005). Among these five histologies, 49 tumors had GSK3β mutations and were positive for PD-L1, and the top mutated residues were H310Q (n=5) and S215L (n=3). Conclusions: In an assessment of over 100,000 tumor samples, GSK3β mutations were most frequently detected in uterine endometrioid carcinoma, non-melanoma skin cancer, uterine neoplasms, and melanoma. GSK3β mutations were associated with a higher frequency of PD-L1 expression in selected tumors. These results may have implications in the selection of patients for treatment with novel targeted therapies such as GSK3β inhibitors and PD-L1 inhibitors. Citation Format: Brittany A. Borden, Joanne Xiu, Yasmine Baca, Pilar Ramos, Francis J. Giles, Andrew Mazar, Fabio Tavora, Howard Safran, Wafik S. El-Deiry, Benedito A. Carneiro. Glycogen synthase kinase-3 beta (GSK-3b) genomic alterations and increased programmed death-ligand 1 (PD-L1) expression in advanced malignancies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5292.

Targeted Detection of Cyclooxygenase-1 in Ovarian Cancer.

Overexpression of cyclooxygenase-1 (COX-1) is associated with the initiation and progression of ovarian cancer, and targeted imaging of COX-1 is a promising strategy for early detection of this disease. We report the discovery of N-[(5-carboxy-X-rhodaminyl)but-4-yl]-3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propenamide (CMP) as the first COX-1-targeted optical agent for imaging of ovarian cancer. CMP exhibits light emission at 604 nm (λmax), thereby minimizing tissue autofluorescence interference. In both purified enzyme and COX-1-expressing human ovarian adenocarcinoma (OVCAR-3) cells, CMP inhibits COX-1 at low nanomolar potencies (IC50 = 94 and 44 nM, respectively). CMP's selective binding to COX-1 in OVCAR-3 cells was visualized microscopically as intense intracellular fluorescence. In vivo optical imaging of xenografts in athymic nude mice revealed COX-1-dependent accumulation of CMP in COX-1-expressing mouse ovarian surface epithelial carcinoma (ID8-NGL) and OVCAR-3 cells. These results establish proof-of-principle for the feasibility of targeting COX-1 in the development of new imaging and therapeutic strategies for ovarian cancer.

Solid tumors of ovary: An institutional experience of three years

Majority of ovarian tumors arise from surface epithelium, germ cell layers and stromal tissue. They give a wide spectrum of tumours which account for fifth most common cause of cancer related deaths in women. Fortunately most of the ovarian tumours are cystic and benign in nature. Solid tumours of ovary are histopathologically very complex and most of metastatic tumours and surface epithelial carcinoma are solid in nature. Solid ovarian tumours can see in all age groups. In our study we found Germ cell tumors were the commonest followed by sex cord stromal tumors. In the view of their complexity and malignant nature clinicians and radiologists should require special attention while exploring the solid ovarian tumours.

Epithelial-mesenchymal transition in serous and mucinous epithelial tumors of the ovary.

The concept of epithelial-mesenchymal transition (EMT) in cancer origin, progression, and metastasis is of recent origin and not fully understood. So far, many cell culture studies have been done to investigate the role of EMT in epithelial ovarian cancer, but only a few human studies have been conducted. The aim of the study is to study the expression of E-cadherin and vimentin in serous and mucinous tumors of the ovary and to compare their expression in benign and malignant serous and mucinous ovarian tumors. This study was a prospective study done on 60 patients with a histological diagnosis of serous and mucinous ovarian malignancy. The study was conducted in the Department of Pathology and Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi. The expression of epithelial marker E-cadherin and mesenchymal marker vimentin was studied in each of the tumors. Unpaired t-test/Mann-Whitney test, Chi-Square test/Fisher's exact test, and Kolmogorov-Smirnov test were used. Of the total 60 cases included in the study, 30 benign and 30 malignant cases of serous and mucinous tumors were taken. Of the 30 benign cases, 22 cases (73.3%) were that of serous cystadenomas, whereas 8 (26.67%) cases were of mucinous cystadenomas. Among the malignant cases, 21 cases (70%) were serous surface epithelial ovarian carcinoma, whereas 9 (30%) were mucinous surface epithelial ovarian carcinoma. Subsequently, the malignant cases were graded according to their glandular differentiation. Immunohistochemistry was performed in each of the 60 cases. In the malignant cases with increasing grade of the tumor, a reduced expression of E-cadherin and an increased expression of vimentin were seen in the epithelial cells.

Histopathological patterns of primary malignant ovarian neoplasms in different age groups in Almadinah Almunawwarah region, KSA.

ObjectivesIn the literature, the epidemiological pattern of ovarian neoplasms in different age groups in the Almadinah Almunawwarah region in KSA has not been completely elucidated. Moreover, an unusually frequent diagnosis of adult granulosa cell tumour (AGCT) has been observed in patients in Almadinah Almunawwarah, KSA. This study aimed to describe the pattern of ovarian neoplasms in different age groups in the Almadinah Almunawwarah region with particular emphasis on AGCT.MethodsHistopathological records of all ovarian specimens diagnosed from 2011 January to 2016 December were collected from the Maternity and Children Hospital in Almaadinah Almunawwarah, KSA. Hematoxylin and eosin (HE)-stained microscopic slides of serous and mucinous epithelial borderline neoplasms and of malignant epithelial, sex cord-stromal and germ line neoplasms were identified and examined. The tissue sections from the AGCT were stained immunohistochemically with BRCA-1 antibody.ResultsA total of 301 ovarian specimens were obtained. Of the specimens, 217 (72%) were neoplastic and 84 (28%) were non-neoplastic. In total, 135 (63%) of the neoplastic specimens were benign, 16 (7%) were borderline tumours, and 66 (30%) were malignant tumours. Moreover, 41 (62%) of the malignant tumours were surface epithelial carcinomas, 17 (26%) were sex cord-stromal tumours, and 8 (12%) were germ cell tumours. The incidence of AGCT was unusually high, which accounts for 26% (16/66) of all malignant ovarian neoplasms. Altered BRCA-1 expression was observed in only two specimens.ConclusionIn this study, malignant ovarian neoplasms accounted for 30% of all neoplastic ovarian specimens, and the incidence of AGCT was remarkable. Such tumours did not show a significantly altered expression of BRCA-1. Further studies must be conducted to explore the underlying molecular causes of this condition.

The Association Between Endometriosis and Surface Epithelial Ovarian Tumors: A Review of Pathological Data

Background: Endometriosis is a prevalent benign condition arising from female reproductive system and affects about 7% to 10% of females. The association of this disorder with epithelial ovarian tumors has been a matter of interest in gynecology. Objectives: The present study was conducted to assess the association between endometriosis and different types of surface epithelial ovarian tumor. Methods: Microscopic slides of 182 cases with the diagnosis of surface epithelial ovarian carcinoma and borderline tumor from 2007 to 2014 were reviewed for the presence of endometriosis in a tertiary gynecological center. Additional data included age, tumor size and laterality, site of endometriosis, presence of atypical endometriosis, and concomitant uterine endometrial carcinoma. Results: Endometriosis was found in 32 out of the 182 (17.58%) of reviewed ovarian epithelial tumor cases. They included endometrioid carcinoma (46.87%), clear cell carcinoma (18.75%), borderline epithelial tumor (31.25%), and low-grade serous papillary carcinoma (3.12%). Conclusions: Endometrioid and clear cell types of ovarian tumors were most frequently associated with endometriosis.

Does molecular profiling of tumors using the Caris molecular intelligence platform improve outcomes for cancer patients?

We evaluated the effect of tailoring treatments based on predictions informed by tumor molecular profiles across a range of cancers, using data from Caris Life Sciences. These included breast carcinoma, colorectal adenocarcinoma, female genital tract malignancy, lung non-small cell lung cancer, neuroendocrine tumors, ovarian surface epithelial carcinomas, and urinary tract cancers.Molecular profiles using mostly immunohistochemistry (IHC) and DNA sequencing for tumors from 841 patients had been previously used to recommend treatments; some physicians followed the suggestions completely while some did not. This information was assessed to find out if the outcome was better for the patients where their received drugs matched recommendations.The IHC biomarker for the progesterone receptor and for the androgen receptor were found to be most prognostic for survival overall. The IHC biomarkers for P-glycoprotein (PGP), tyrosine-protein kinase Met (cMET) and the DNA excision repair protein ERCC1 were also shown to be significant predictors of outcome. Patients whose treatments matched those predicted to be of benefit survived for an average of 512 days, compared to 468 days for those that did not (P = 0.0684). In the matched treatment group, 34% of patients were deceased at the completion of monitoring, whereas this was 47% in the unmatched group (P = 0.0001).

Pathology of Ovarian Cancer: Recent Insights Unveiling Opportunities in Prevention.

Ovarian carcinomas were formerly referred to as "surface epithelial carcinomas," reflecting the belief that they all arise from the ovarian surface epithelium. It is now appreciated that most ovarian carcinomas originate from either fallopian tube or endometriotic epithelium, and how we approach prevention will thus differ between histotypes. The 5 histotypes of ovarian carcinoma (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous, in descending order of frequency) can be reproducibly diagnosed, and are distinct disease entities, differing with respect to genetic risk factors, molecular events during oncogenesis, patterns of spread, and response to chemotherapy.

Cationic dendritic starch as a vehicle for photodynamic therapy and siRNA co-delivery

Cationic enzymatically synthesized glycogen (cESG) is a naturally-derived, nano-scale carbohydrate dendrite that has shown promise as a cellular delivery vehicle owing to its flexibility in chemical modifications, biocompatibility and relative low cost. In the present work, cESG was modified and evaluated as a vehicle for tetraphenylporphinesulfonate (TPPS) in order to improve cellular delivery of this photosensitizer and investigate the feasibility of co-delivery with short interfering ribonucleic acid (siRNA). TPPS was electrostatically condensed with cESG, resulting in a sub-50nm particle with a positive zeta potential of approximately 5mV. When tested in normal ovarian surface epithelial and ovarian clear cell carcinoma cell culture models, encapsulation of TPPS in cESG significantly improved cell death in response to light treatment compared to free drug alone. Dosages as low as 0.16μM TPPS resulted in cellular death upon illumination with a 4.8J/cm2 light dosage, decreasing viability by 96%. cESG-TPPS was then further evaluated as a co-delivery system with siRNA for potential combination therapy, by charge-based condensation of an siRNA directed at reducing expression of manganese superoxide dismutase (Sod2) as a proof of principle target. Simultaneous delivery of TPPS and siRNA was achieved, reducing Sod2 protein expression to 48%, while maintaining the photodynamic properties of TPPS under light exposure and maintaining low dark toxicity. This study demonstrates the versatility of cESG as a platform for dual delivery of small molecules and oligonucleotides, and the potential for further development of this system in combination therapy applications.

Diagnostic and Prognostic Significance of Ki-67 Immunohistochemical Expression in Surface Epithelial Ovarian Carcinoma.

The Surface Epithelial Ovarian Carcinoma (SEOC) at the moment of diagnosis, the disease is extended beyond the structures of the pelvis. Ki-67 is one of the prognostic marker which determines the growth fraction of a tumour and its over expression is associated with malignancy, tumour aggression, reserved prognosis and metastasis. To evaluate the proliferative activity using Ki-67 immuno-staining in SEOC and to correlate with histological subtype, grade, Federation of Gynecology and Obstetrics (FIGO) stage, CA125 levels for diagnostic and prognostic purpose. The study was conducted in JSS Medical College and Hospital, JSS University, Mysuru. It was a descriptive cross-sectional study involving 40 cases of SEOC over a period of two years. The proliferation expression related to Ki-67 antigen was evaluated by immunohistochemical monoclonal MIB-1 antibody. In each case, the Ki-67 labeling index (Ki-67 LI) was articulated as percentage of positively stained cells using high power objective of the microscope (x400). Among the 40 carcinomas, 26 were serous, five mucinous, four each of clear cell and undifferentiated and one transitional cell carcinoma. A total of 75% were high grade tumours. High Ki-67 LI was associated with high grade tumours (69.9%), high grade serous tumours (65.34%) and advanced FIGO staging (70.6%) with the p-value of <0.001. CA 125 levels did not have a significant correlation with Ki-67 LI. Ki-67 is an exceptionally a cost effective marker to determine the growth fraction of a tumour cell population. In SEOC histological grade and FIGO stage when combined with Ki-67 LI in histopathology report would help in diagnostic differentiation of subtypes, prognostication, deciding the need for adjuvant chemotherapy and in predicting survival analysis.

Expression of p53 and CD34 in Surface Epithelial Tumors of Ovary

Ovarian cancer accounts for 3 % of all cancers in females (1) . Owing to diagnostic difficulty of ovarian cancers at early stage, most of them are diagnosed when they are at metastatic stage, thus they account for increased number of deaths occurring in women due to genital tract tumors. Ovarian Carcinomas are currently divided into Type I ( low grade) and Type II ( high grade ) tumours. (1) p53 and CD34 have been reported to play an important role in the progression of ovarian cancer. However, only few studies focus on their expression in benign surface epithelial tumors compared to malignant surface epithelial tumors and further low grade tumors compared to high grade tumors in the malignant category. Tumour angiogenesis, evaluated by CD34 expression as intratumoral microvessel density and CD34 intensity index could be an important predictor of the aggressive nature of high grade ovarian carcinoma. Overexpression of p53 in ovarian tumors of both low-grade and high-grade ovarian tumors has been found to be associated with poor prognosis in most but not all studies. (2) In present study, Mean microvessel density, CD34 intensity index and p53 proportion scoring of High grade tumors was statistically significantly higher than Low grade tumors (p value <0.05). Infact, immunohistochemical staining for p53 has been utilized as a surrogate marker for mutational analysis in the diagnostic workup of carcinomas of multiple sites including ovarian cancers. (3) Implication of p53 and CD34 in predicting the metastatic potential of ovarian surface epithelial carcinomas has to be further analysed with larger sample size.

A pure primary transitional cell carcinoma of the ovary: A rare case report with literature review

Primary transitional cell carcinoma (TCC) of the ovary is a rare and recently recognized subtype of ovarian surface epithelial-stromal cancer. Pure forms of the TCC ovary account for only 1% of surface epithelial carcinomas. The clinical presentation is indistinguishable from other types of ovarian cancers. They have a favorable response to chemotherapy than other surface epithelial cancers. We report a case of 55-year-old woman who presented with a hard mass in the abdomen. Computed tomography-diagnosed it as a carcinoma of the ovary. Tumor was immunoreactive with Wilms’ tumor protein-1 and nonreactive with cytokeratin 7 (CK7) and CK20. Histopathology diagnosis of primary TCC of the ovary was made. These tumors are needed to be differentiated from metastatic TCC from other sites and undifferentiated carcinomas of ovaries. Clinical features and immunohistochemistry are helpful. Surgical resection is the primary therapeutic approach followed by standardized chemotherapy.

Impact of MDSC emergence during ovarian cancer in cytokine-deficient mice. (TUM6P.1011)

Abstract We have been studying the emergence of myeloid-derived suppressor cells (MDSCs) following i.p. transfer of ID8 cells (mouse ovarian surface epithelial cell carcinoma) into intact, syngeneic, C57BL/6J (wild type, WT) mice. Our current work studies the impact of the cytokine (CK) environment on ID8 expansion and MDSC emergence in the peritoneal cavity (PerC). We wanted to determine if particular pro- (IFNg) or anti- (IL4, IL10) inflammatory CKs were drivers of disease in this model. We found that, relative to WT mice, the development of hemorrhagic ascites was accelerated in IL10-/-, IL4-/-, and IFNgR-/- mice. The greatest percentage and number of MDSCs was observed in IL10-/- mice, which also had the greatest expansion of ID8 cells. ID8 triggered a marked increase in PerC Mfs, particularly in the IL10-/- mice, and lymphocytes, particularly in the IFNgR-/- and IL4-/- mice. However, for all mice, the percent representation of B cells in the total PerC cell pool declined markedly, particularly in the IL10-/- mice (&amp;gt; 70%). Interestingly, beyond the peritoneal locus of disease, both B and T lymphocyte percentages dropped in the spleens of all mice. This was seen without a concomitant increase in the number of MDSCs or appearance of ID8 in the spleen. These observations reinforce that inflammation drives MDSC emergence and suggest that changes in lymphocyte populations could serve as biomarkers for assessing ovarian cancer.

A rare presentation of a necrotic undifferentiated ovarian carcinoma in an adolescent girl causing a diagnostic dilemma

Undifferentiated carcinoma is rare tumors with the worst prognosis than any type of surface epithelial carcinoma. They are common in fourth and fifth decade. In most cases, these spread beyond the ovary at the time of diagnosis and cannot be optimally debulked. A 17 years unmarried girl presented with an ovarian tumor, which on ultrasonography measured 9.9 cm Χ 6.7 cm Χ 6.6 cm arising from the left ovary and extending into the pelvis. Right ovary and other organs were unremarkable. Lab investigations: S. alpha fetoprotein (S.AFP) - 0.85 (0.5-2 ng/ml), B - human chorionic gonadotropin - 1.2 (<5 mIU/ml), cancer antigen - 125-127 (35 units/ml), carcinoembryonic antigen - 3.26 (<2.5 ng/ml). At histology, the tumor had undergone extensive areas of necrosis. The focal viable areas showed a poorly differentiated aggressive tumor. Extensive inter-observer variability in diagnosis existed. S.AFP levels were normal. AE1/AE3, EMA were positive while the rest IHC markers did not contribute to any specific diagnosis. The tumor was then diagnosed as undifferentiated carcinoma of the ovary. She received 3 cycles of cisplatin-based chemotherapy postoperatively. Two months later, she developed a metastatic nodule near the umbilicus. She succumbed to her illness within 3 months of diagnosis.

Abstract LB-171: Concordance between protein expression and mRNA expression in the large cohort of cancer patients

Abstract Introduction: Immunohistochemical (IHC) analysis of protein expression in clinical specimens has been invaluable in diagnosing, monitoring and guiding treatment in cancer patients. This approach, however, has its limitations including the difficulty to obtain robust and reliable antibodies, the semi quantitative nature of the assay, subjectivity of intensity call, and the lack of specificity to detect clinically relevant isoform expression in tumor specimen. In light of these limitations, RNA expression may be a useful replacement or a complementary approach to IHC in clinical settings. In this study, we compared the concordance between IHC and mRNA expression levels as measured by microarray using a large cohort of cancer patients spanning multiple lineages. Methods: 10246 patient samples that included 40 tumor types were utilized in this study. Transcript and protein expression levels were measured for ESR1, AR, KIT, ERBB2 (Her2), RRM1, and ERCC1. Transcript levels were measured by Illumina's HumanHT-12 microarray (v4), and IHC was performed using the following antibodies: SP1 (ESR1), AR27 (AR), 4B5 (Her2), 8F1 (ERCC1), anti-CD117 polyclonal (KIT), and 10526-1-AP (RRM1). Results: We observed a significant correlation between ERBB2, ESR1, and KIT with IHC data. Of the 3 probes on the microarray measuring ERBB2, only one probe mapping to the 3’ end of the two ERBB2 isoforms showed significant association with IHC data. For KIT, IHC and mRNA expression correlated well across, thymic carcinomas, poorly differentiated neuroendocrine tumors, melanoma, GIST, and head and neck cancer. For ESR1, significant correlations were observed for uterine sarcoma, endometrial carcinoma, and breast adenocarcinoma. Cervical cancers and ovarian surface epithelial carcinomas showed diminished association, and there was a lack of association in NSCLC and neuroendocrine carcinoid tumors. For AR, we observed strong correlation only in prostate tumors. ERCC1 and RRM1 mRNA expressions did not correlate well with protein expression in any of the tumor lineages examined. Conclusion: These observations suggest that measuring mRNA via microarray has the potential to serve as a surrogate for IHC in clinical setting. The mixed associations observed for some of the genes exhibited lineage specificity suggesting that the relation between microarray results and IHC may be driven by the tissue-specific expression of isoforms, differential expression of genes in the stromal cells, and the technical limitations of each platform including the specificity of either the probes used to measure mRNA or antibodies used to measure protein expression. As such, combining the two platforms in the clinical setting may provide a more complete assessment of gene expression in tumor samples. Citation Format: Anatole Ghazalpour, Wangjuh Sting Chen, Wenhsiang Wen, Zoran Gatalica, Ryan Bender. Concordance between protein expression and mRNA expression in the large cohort of cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-171. doi:10.1158/1538-7445.AM2014-LB-171

Primary Fallopian-Tube Carcinoma

Background: Primary Fallopian tube carcinoma (PFTC) is a rare tumor in postmenopausal women, which clinically and histologically resembles surface epithelial ovarian carcinoma (SEOC). PFTC has a worse prognosis than SEOC as it is not routinely suspected; therefore, treatment may be delayed. Case: The case of a 48-year-old postmenopausal woman who presented with gradually increasing lower abdominal pain is reported. Ultrasound revealed a mass of left tubo-ovarian origin, with the possibility of an ovarian tumor. Results: Total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) was performed, and histologic findings established PFTC. The patient was followed-up for 2 years and remained free of disease. Conclusions: PFTC is a rare gynecologic malignancy. Histopathologic confirmation is mandatory for diagnosis and management of such patients of this condition. (J GYNECOL SURG 30:111)