High CA19-9 Level Research Articles

Characteristics of Peripheral Immune Function in Reproductive Females with Uterine Leiomyoma.

Inflammation and immunity are thought as risk factors for uterine leiomyoma; however, detailed reports on this topic are scarce. The present study aimed to analyze the characteristics of immune function and clinical significance of circulating CD4/CD8 T, NK, and γδ T cells in reproductive females with uterine leiomyoma. We analyzed the above-mentioned cells in 30 reproductive females with uterine leiomyoma and 68 healthy females using flow cytometry. After that, the correlation between function of immune cells and clinical phenotypes was analyzed. Compared with healthy controls, central memory (CM) CD4/CD8 T cells as well as Treg and Tfh cells were notably increased in leiomyoma patients; however, NK and γδ T cells were decreased in patients. Moreover, such alterations of these cells in patients with leiomyoma were associated with shorter menstrual cycles, longer menstrual period, anemia, pelvic lesions, more and larger myomas, and higher levels of CA125. Additionally, the increased Tfh1/Tfh2 ratio and Tfh17 were significantly associated with longer menstrual period, more myomas, and higher CA125 levels independent of age in patients with uterine leiomyoma. In conclusion, hallmarks of peripheral immune function are remarkably correlated with clinical phenotypes in reproductive females with uterine leiomyoma. This preliminary work may provide proof-of-concept for evaluating efficacy of treatment and prognosis of reproductive females with uterine leiomyoma with the help of quantitative analysis of peripheral immune function, which may inspire performing further investigations on the relevance of immune function with different diseases.

The Prognostic Value of Preoperative Serum CA125 in Endometrioid Endometrial Cancer with Cervical Stromal and Parametrial Invasion

Background: Although endometrial cancer is not ranked among the ten most common cancer types in Iran, it is the 12th most prevalent in women and the third most common cancer of the female genital tract after breast and ovarian cancer. The mortality rate of endometrial cancer in Iran is 0.6 in 100,000 persons. Several studies have evaluated the correlation of preoperative CA125 in endometrial cancer with several surgicopathologic and prognostic variables, disease recurrence, and the need for lymphadenectomy. Recent data have suggested adjuvant extrafascial hysterectomy after neoadjuvant therapy instead of the initial radical hysterectomy for locally advanced disease. Therefore, it would be helpful to use a preoperative assessment, including serum CA125 measurement to predict the extent of the disease and plan a less complicated therapy. Objectives: To evaluate the cut-off value of CA125 in parametrial and cervical stromal invasion of endometrioid endometrial cancer. Methods: A sample of 128 endometrial cancer cases, surgically staged from 2012 to 2018 in Imam Hossein Hospital were evaluated. According to the exclusion criteria, 82 cases were finally analyzed. A receiver operating characteristic (ROC) curve was used to determine the cut-off value of preoperative CA125 for parametrial and cervical stromal involvement. Results: A high preoperative CA125 level was significantly associated with advanced disease stage, cervical stromal invasion, pelvic lymph node metastases, and higher grade (P < 0.05); the test showed a marginally significant correlation for parametrial invasion, which may be due to sample size limitation (P = 0.058). However, the correlation between CA125 and myometrial/lymphovascular invasions were not statistically significant (P = 0.112 and P = 0.168, respectively). The optimal cut-off value for preoperative CA125 was 45.5 u/mL in parametrial invasion (100% sensitivity, 89% specificity, 33.3% positive predictive value, and 100% negative predictive value), and 41.9 u/mL for cervical stromal invasion (87.5% sensitivity, 87.8% specificity, 43.75% positive predictive value, and 98.48% negative predictive value). Conclusions: Primary radical surgery may not be the first treatment approach in cervical/parametrial involvement. Neoadjuvant (chemo)radiotherapy and adjuvant extrafascial hysterectomy could be an alternative approach with fewer complications. Using preoperative CA125 along with physical examination and imaging modalities would be helpful in this regard. More investigations are needed to assess an agreed cut-off value for preoperative CA125 and endometrial cancer extension.

Role of optimal cytoreduction in patients with dysgerminoma

BackgroundDysgerminomas are malignant ovarian germ-cell tumors that typically affect young women. Although these tumors have an excellent response to chemotherapy, surgery is an integral part of primary treatment.ObjectiveTo evaluate outcomes...

1285 Elevated CEA and CA 19-9 Producing Carcinoma: Think Beyond the Digestive System!

INTRODUCTION: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are validated and well-known tumor markers for colorectal and pancreatic malignancies but data concerning these markers in bladder carcinoma are limited. We report a rare case of bladder carcinoma with metastasis to the bone marrow producing very high serum levels of CEA and CA 19-9. CASE DESCRIPTION/METHODS: A 68-year-old man with a medical history of hypertension, COPD presented with altered mental status. The patient further reported anorexia, unintentional weight loss of 50 lbs and intermittent hematuria over the last few months. He was confused but hemodynamically stable on presentation. Initial laboratory data showed pancytopenia, ALP of 712 U/L with normal transaminases and bilirubin, urine microscopy showed &gt;100 red blood cells/HPF. A CT scan of the abdomen showed bilateral hydronephrosis with thickening of the urinary bladder and diffusely abnormal bone marrow. Bone marrow biopsy showed poorly differentiated metastatic carcinoma with positive immunohistochemical (IHC) stains for cytokeratin (CK)7 and CK20. In addition, very high levels of tumor markers CA19-9 42,635 U/ml, CEA 347 ng/ml raised a possibility of origin from the gastrointestinal or pancreatobiliary system. Subsequently, upper endoscopy, colonoscopy, EUS, and magnetic resonance cholangiopancreatography (MRCP) were performed and results were unremarkable. Finally, a cystoscopy was performed showing multiple papillary tumors throughout the bladder. Unfortunately, the patient died before any further workup and therapeutic interventions were initiated. DISCUSSION: Elevated levels of CEA and CA19-9 have been demonstrated in TCC of the bladder. The specificity of CEA for diagnosis of colorectal cancer is 89 percent while the specificity of CA 19-9 for pancreatic cancer goes up to 85% at a serum level &gt;37 U/ml but neither are useful tools in the primary diagnosis of TCC. The pattern of staining with the CK20 and CK7 may be helpful in narrowing the diagnostic spectrum, but both can show positivity in pancreatobiliary and urothelial cancers. IHC allows limited determination of the tissue of origin in poorly differentiated carcinomas due to atypical staining patterns. In conclusion, when CEA and CA19-9 serum levels are elevated, a gastrointestinal malignancy should be excluded and one should be mindful of the existence of CEA and CA19-9 producing TCC and thus examine the urologic tract.

Chemotherapy Toxicity in BRCA Mutation Carriers Undergoing First-Line Platinum-Based Chemotherapy.

BRCA mutations are the most frequent mutations causing homologous recombination defects in epithelial ovarian cancers (EOC). Germline mutation carriers are heterozygous for the mutation and harbor one defective allele in all cells. This has been hypothesized to cause increased susceptibility to DNA damage in healthy cells as well as neoplastic ones. Our objective was to assess chemotherapy-associated toxicities in patients with epithelial ovarian cancer with and without a germline BRCA mutation. A retrospective cohort study of patients with EOC receiving first-line platinum-based chemotherapy at a single center between 2006 and 2016. Indices of chemotoxicity, including blood counts, transfusion requirements, granulocyte colony-stimulating factor (gCSF) prescriptions, episodes of febrile neutropenia, and treatment delays were compared for BRCA mutation carriers and noncarriers. A total of 90 women met the inclusion criteria, including 31 BRCA mutation carriers (34%) and 59 noncarriers (66%). Mean hemoglobin, neutrophil count, and platelet counts during treatment were comparable for the two patient groups. There was a trend toward a higher frequency of hematological events in BRCA mutation carriers (neutropenia <1500 per mL: 6% vs. 0%, p = .12; thrombocytopenia <100,000 per mL: 23% vs. 9%, p = .07), but these differences were not statistically significant. Similarly, no significant differences were found in surrogates of bone marrow toxicity such as blood transfusions, use of gCSF, episodes of febrile neutropenia, or treatment delays. BRCA mutation carriers and noncarriers receiving first-line platinum-based chemotherapy for EOC have similar hematologic toxicity profiles. Clinicians treating these patients can be reassured that chemotherapy dosing or schedule do not require adjustment in patients carrying BRCA mutations. Patients with ovarian cancer carrying BRCA mutations are more likely to have serous tumors and present with higher CA125 levels. Germline BRCA mutation status is not associated with increased frequency of adverse hematologic events among patients with ovarian cancer being treated with first-line platinum-based chemotherapy. Germline BRCA mutations are also not associated with more treatment delays or a lower number of courses completed in this patient population. These findings should reassure practitioners engaged in care for patients with ovarian cancer that BRCA mutation status most likely will not affect chemotherapy dosing or schedule.

Abstract 1363: Identifying blood exosomal miRNAs as biomarkers in the diagnosis and prognosis of pancreatic ductal adenocarcinoma

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is of high mortality with a shortage of effective non-invasive biomarkers in the diagnosis and prognosis. Without a proper method to identify reasonable target molecules and their references for normalization, robust and accurate blood miRNA biomarkers have not been reported. We aim to explore the exosomal miRNAs as biomarkers for the diagnosis and prognosis of PDAC with sufficient biological insights and robustness. Materials and Methods: miRNA-seq was performed on miRNAs extracted from blood exosomes. 16 non-metastatic PDAC, 11 metastatic PDAC and 15 pancreatitis patients were enrolled in 2017 as the training set. Another 18 non-metastatic PDAC, 12 metastatic PDAC and 18 pancreatitis patients were enrolled in 2018 as the testing set. Bayesian network was built on the levels of miRNAs to identify candidate biomarkers with biological insights. The area under the curve (AUC) of receiver operating characteristic (ROC) was used to measure the accuracy of each pair of miRNAs. Results: The exosomal miRNA from the plasma of these patients with PDAC or pancreatitis has been successfully extracted and sequenced. The Bayesian network consisted of 337 nodes and 713 edges. The quotient of miR-95-3p (a “consequence” of “cancer”) over miR-26-5p (a “cause” of “pancreatitis”) performed 81.5% sensitivity and 93.3% specificity in the training cohort, and 86.7% sensitivity and 100% specificity in the testing cohort respectively. Furthermore, considering either high serum level of CA19-9 or the quotient of miR-95-3p/miR-26-5p as PDAC, the sensitivity increased to 96.5%, and the specificity was maintained at 96.9%. In addition, miR-335-5p level in blood exosome could predict metastasis with a mean accuracy of 77.2%, and showed strong relation with overall survival after surgeries. Conclusions: MiRNAs biomarkers from blood exosomes in differential diagnostics and prognosis are identified and rationale by Bayesian network. Integration of biomarkers of various molecular types could enhance the diagnostic accuracy beyond single molecular types. Blood exosomal miRNAs could be applied to monitor the development of PDAC. Citation Format: Shiwei Guo, Huan Wang, Hao Qin, Dadong Zhang, Zhuo Shao, Yanan Zhang, Bin Song, Xiaoya Xu, Jing Shen, Zishuo Chen, Xiaohan Shi, Suizhi Gao, Yaqi Pan, Fugen Li, Gang Jin. Identifying blood exosomal miRNAs as biomarkers in the diagnosis and prognosis of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1363.

Abstract 2370: Synergistic effect of carboplatin on farletuzumab (FAR) tumor cell killing via downregulation of the humoral immunosuppressive CA125 protein and enhanced antibody dependent cellular cytotoxicity (ADCC)

Abstract Farletuzumab (FAR) is a humanized monoclonal antibody (mAb) that targets folate receptor alpha (FRA), a cell surface protein highly overexpressed on a large number of cancers. Clinical evidence suggests that FAR enhances the anti-tumor effects of carboplatin and taxane in ovarian cancer patients whose tumors express low CA125 levels. In light of the recent evidence that CA125 has a direct effect on suppressing the humoral immune mechanisms [antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC)] of FAR (1, 2) and the findings that chemotherapeutic agents can enhance the ADCC activity of certain mAbs, we tested the potential synergistic effects that carboplatin may have on FAR immune effector function. Here we show the immunosuppressive effects that CA125 has on FAR-mediated tumor cell killing in vivo and demonstrate that carboplatin is able to suppress cell surface CA125 expression leading to enhanced FAR ADCC on FRA-expressing ovarian tumor cells. CA125 has been previously found to suppress FAR-mediated tumor cell killing in vitro. To determine its effect in vivo, we tested single agent FAR against isogenic tumor cells in mouse xenografts. OVCAR-3 is a FRA positive ovarian tumor cell line that expresses high levels of CA125 on its cell surface. A CA125 shRNA knockdown line (OV-KD) has been previously generated and shown to be more susceptible to FAR ADCC than its parental counterpart. Xenograft studies using these lines found that FAR had significant single agent tumor killing in the OV-KD xenografts in contrast to OVCAR-3 xenografts. We next tested FAR in vivo killing when used in combination with carboplatin. These data showed that carboplatin had a synergistic effect when combined with FAR treatment as compared to single agent treatment alone. To determine if this mechanism involved enhanced ADCC, we conducted similar studies in vitro whereby OVCAR-3 cells were treated with a sublethal concentration of carboplatin for 72 hrs, washed and then tested for FAR ADCC killing. These data found that FAR had enhanced ADCC activity on carboplatin treated cells as compared to untreated cells. Finally, to explore the potential mechanism by which this effect may occur, we examined the steady-state levels of both the mannose-6-phosphate receptor (M6PR), reported to be upregulated by chemotherapeutic drugs leading to enhanced ADCC via higher granzyme B uptake and the CA125 immunosuppressive factor. Our data found that both M6PR and CA125 expression were significantly suppressed following carboplatin exposure. These data support a mechanism by which carboplatin may enhance the humoral immune response for FAR and potentially other anti-tumor mAbs via downregulation of the immunosuppressive CA125 protein. 1. OncoTarget 8:66747-57, 20172. 2. EJI 201847707, 2018 Citation Format: J. Bradford Kline, Keiji Furuuchi, James Fulmer, Jennifer McDonough, Luigi Grasso, Nicholas C. Nicolaides. Synergistic effect of carboplatin on farletuzumab (FAR) tumor cell killing via downregulation of the humoral immunosuppressive CA125 protein and enhanced antibody dependent cellular cytotoxicity (ADCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2370.

Role of magnetic resonance DTI in PDAC evaluation

Adipophilin is a lipid droplet-associated protein, and its expression has been correlated with aggressive clinical behavior in some types of carcinomas, though its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified. This study aimed to evaluate the role of adipophilin in PDAC.By immunohistochemical staining using tissue microarrays, we analyzed the expression profiles of adipophilin in 181 consecutive PDAC patients who underwent macroscopic margin-negative resection from January 2008 to December 2015. Overall survival (OS) and recurrence-free survival (RFS) were compared based on adipophilin expression, and the risk factors for OS, RFS, and early recurrence (within 6 months) were analyzed.Of the 181 evaluated patients, 51 (28.2%) were positive for adipophilin expression. A histopathological grade of 3 (p = 0.0012), higher CA19-9 level (p = 0.0016), and R1 status (p = 0.028) were significantly associated with adipophilin-positive patients who had significantly poor OS and RFS compared to those associated with adipophilin-negative patients (p = 0.0007 and p = 0.0022, respectively). They also showed a significantly higher incidence of early recurrence (p = 0.030), based on multivariate analyses.Adipophilin is a potential independent prognostic marker for PDAC.

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer.

In this study, we investigated the clinical significance of postoperative serum carbohydrate antigen (CA) 19-9 in patients with pancreatic ductal carcinoma (PDAC). A series of 116 patients with macroscopically curative PDAC resection was retrospectively evaluated. The cut-off level for elevated postoperative CA 19-9 was 37 U/ml. Patients with high postoperative CA19-9 levels had a significantly poorer prognosis than patients with normal postoperative CA19-9 levels, as revealed by the log-rank test. Multivariate analysis identified R1 resection and preoperative serum CA19-9 level ≥400 U/ml independently predicted elevated postoperative CA 19-9 levels. R1 resection and preoperative serum CA19-9 ≥400 U/ml were significantly associated with the recurrence of peritoneal dissemination and hepatic metastasis, respectively, within one year of operation. Elevated postoperative serum CA 19-9 level was associated with a poor prognosis and reflected positive resection margins and high preoperative CA 19-9 levels, which indicated presence of occult distant metastasis in patients with PDAC.

Mutant KRAS and TP53 with high mutation allelic frequency in ctDNA as poor outcome predictors in metastatic pancreatic cancer.

e15763 Background: This study was to investigate the feasibility and the prognostic value of circulating tumor DNA (ctDNA) in metastatic pancreatic cancer (MPC). Methods: From 2015 to 2018 in our center, 40 MPC patients treated with nab-paclitaxel based first-line chemotherapy were prospectively collected both tumor tissue and blood samples, in which the genomic profiling of 425 genes was identified by next-generation sequencing. High mutation allelic frequency (MAF) was defined &gt; 30% and &gt; 5% in tumor tissue and blood, respectively. Kappa statistics were used to compare mutant (mt) genes in tissue and ctDNA. Progression-free and overall survival (PFS, OS) were assessed with Kaplan-Meier and Cox methods. Results: Among 40 MPC patients, tumor tissue and blood samples were available in 34 and 38 patients for somatic and germline alternation test, respectively. The most commonly mutant gene were KRAS (31/34 in tissue with a median MAF of 29.4%, 29/38 in ctDNA with a mMAF of 8.2%), and TP53 (28/34 in tissue with a mMAF of 31.1%, 25/38 in ctDNA with a mMAF of 7.4%). Moderate agreement was seen between ctDNA and tumor tissue (mt KRAS: κ = 0.54, P = 0.001; mt TP53: κ = 0.74, P &lt; 0.001). Mutation in CDNK2A and SMAD4 genes were detected in 8 and 6 patients in tissue and ctDNA, respectively. Germline alternation was found in 7 genes in 9 patients (9/40). High MAF of mt KRAS (r = 0.51, P = 0.005) or mt TP53 (r = 0.50, P = 0.005) in ctDNA was correlated with high CA199 levels (&gt; 5000 u/ml) at baseline. MT KRAS in tissue with high MAF was associated with poor OS (high 7.5m vs low 10.1m, P = 0.001) in univariate and multivariate analyses (HR 3.87, 95%CI 1.47 to 10.19). Univariate analyses showed mt KRAS and mt TP53 in ctDNA with high MAF were associated with poor PFS ( KRAS and TP53: high 3.4m and 3.0m vs low 6.1m and 5.7m, P = 0.001 and P = 0.004, respectively) and OS ( KRAS and TP53: high 5.3m and 5.3m vs low 12.6m and 10.1m, P &lt; 0.001, respectively). The presence of ctDNA in any above four mt driver gene with high MAF was associated with poor PFS (HR 3.79, 95%CI 1.71 to 8.42) and OS (HR 7.21, 95%CI 2.69 to 19.34) in multivariate COX model, when adjusted by age, sex, tumor differentiation, and baseline CA199 level. Conclusions: The presence of mt KRAS and mt TP53 with high MAF in ctDNA was associated with worse PFS and OS in MPC patients. Peripheral ctDNA testing demonstrated an alternative promising prognostic biomarker for MPC patients before treatment.

Patient-Friendly Summary of the ACR Appropriateness Criteria: Staging and Follow-up of Ovarian Cancer

Ovarian cancer is a cancer that begins in the ovary or the adjacent fallopian tube and can spread (metastasize) to the peritoneum (a thin membrane that lines the abdominopelvic cavity), liver, spleen, lymph nodes, and lungs. Imaging tests are used to diagnose and stage ovarian cancer both before and after initial treatment. Staging helps plan treatment. Treatment options include surgical removal of the cancer, chemotherapy, and radiation therapy. Chemotherapy and radiation may be used before surgery to hopefully shrink tumors enough for surgical removal. Monitoring for recurrence includes laboratory test (high CA-125 levels) or a clinical examination. Contrast-enhanced CT of the pelvis, abdomen, and sometimes the chest is the most appropriate imaging technique for diagnosing and staging initial and recurrent ovarian cancer. CT detects local and metastatic tumors and can be used for guided biopsy to diagnose suspicious masses. CT may not find small tumors, especially in the intestines, peritoneum, and lymph nodes. A PET/CT scan using fluorine-18-2-fluoro-2-deoxy-D-glucose is used for staging cancer that has metastasized or reoccurred. PET scans are not appropriate for initial diagnosis because they may give false-negative results. PET scans detect metabolic activity (tumors have high metabolism) and help locate microscopic tumors not found on routine CT. Contrast-enhanced MRI is not used often in ovarian cancer imaging; MRI is a long procedure; if the individual moves the image is not accurate. MRI is appropriate for inconclusive CT scans (borderline tumor findings) and helps preserve fertility (no radiation exposure). If kidney disease prevents contrast-enhanced imaging, both CT and MRI without contrast may be appropriate. See the full appropriateness criteria for this topic at https://acsearch.acr.org/docs/69378/Narrative/.

Adipophilin expression is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma: An immunohistochemical analysis

ObjectiveAdipophilin is a lipid droplet-associated protein, and its expression has been correlated with aggressive clinical behavior in some types of carcinomas, though its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified. This study aimed to evaluate the role of adipophilin in PDAC. MethodsBy immunohistochemical staining using tissue microarrays, we analyzed the expression profiles of adipophilin in 181 consecutive PDAC patients who underwent macroscopic margin-negative resection from January 2008 to December 2015. Overall survival (OS) and recurrence-free survival (RFS) were compared based on adipophilin expression, and the risk factors for OS, RFS, and early recurrence (within 6 months) were analyzed. ResultsOf the 181 evaluated patients, 51 (28.2%) were positive for adipophilin expression. A histopathological grade of 3 (p = 0.0012), higher CA19-9 level (p = 0.0016), and R1 status (p = 0.028) were significantly associated with adipophilin-positive patients who had significantly poor OS and RFS compared to those associated with adipophilin-negative patients (p = 0.0007 and p = 0.0022, respectively). They also showed a significantly higher incidence of early recurrence (p = 0.030), based on multivariate analyses. ConclusionsAdipophilin is a potential independent prognostic marker for PDAC.

To assess the utility of proliferative marker Ki-67 in surface epithelial ovarian tumor

Background: Surface epithelial ovarian tumor (SEOT) accounts for more than 90% of all the ovarian tumors and are the most lethal one. Cellular proliferation plays a significant role in the clinical behavior and aggressiveness of ovarian tumor. Proliferative activity of the tumor can be assessed using the proliferative marker Ki-67, which has both diagnostic and prognostic values. Aim and Objective: The aim and objective of this study was to assess the expression of proliferative marker Ki-67 in various SEOT and correlate its level of expression with clinicopathological parameters including the International Federation of Gynecology and Obstetrics (FIGO) staging and preoperative CA-125 level. Materials and Methods: The study was a cross-sectional and observational study carried out in the Department of Pathology, JNMC, Sawangi, Wardha, over 2 years. It included 74 patients with surgically resected specimen of SEOT. Ki-67 immunohistochemistry was performed in all the 74 cases, and the percentage of immunopositive cells was expressed as Ki-67 labeling index (Ki-67 LI). Results: Out of 74 cases, 54 were benign and 20 were malignant which comprised serous and mucinous histological subtypes. Ki-67 expression was found to be positive only in malignant tumors (Ki-67 LI >1%). High Ki-67 LI was associated with high-grade serous cystadenocarcinoma (48.5%), advanced FIGO staging (40.5%), and high CA-125 levels. However, there was no association between Ki-67 LI and histological subtype. Conclusion: Ki-67 is a cost-effective proliferative marker. Therefore, immunohistochemical assessment of Ki-67 expression can be included in routine histopathological report of SEOT for diagnosis and prognostication which will help in better understanding of the biologic behavior of the tumor and modifying treatment strategies.

High CA-125 in Endometrioma: An Unusual Presentation

CA-125 (cancer antigen 125, carcinoma antigen 125, or carbohydrate antigen 125) also known as mucin 16 or MUC16 is a protein of mucin family glycoprotein that is encoded by the MUC16 gene. It is the most frequently used biomarker for ovarian cancer. It may also be elevated in other cancers, including endometrium, fallopian tube, lung, breast and gastrointestinal cancer and in a number of relatively benign conditions, such as endometriosis, menstruation and pregnancy. High plasma levels of more than 200 U/mL are usually suggestive of malignancy but rarely found in benign conditions of female genital tract, like endometriosis. Very high CA- 125 level is suggestive of ovarian malignancy, was noted in case of ovarian endometrioma. This paper describes a case of a 36 years old lady, mother of 2 children, was admitted with large abdominal mass and abdominal pain. CA-125 was found 3500 U/ML. Ovarian malignancy was suspected. During laparotomy, ruptured endometrioma was noted and it was supported by histopathological report which mentioned," No malignancy seen". Endometrioma can't be excluded in high CA-125 level even without features of endometriosis.KYAMC Journal Vol. 9, No.-3, October 2018, Page 139-140

The preoperative serum CA125 can predict the lymph node metastasis in endometrioid-type endometrial cancer

To evaluate the predictive value of preoperative CA125 in extra-uterine disease and its association with poor prognostic factors in endometrioid-type endometrial cancer (EC). A total of 423 patients with pathologically proven endometrioid-type EC were included in the study. The association between preoperative CA125 level and surgical-pathological factors was evaluated. The conventional cut-off value was defined as 35 IU/mL. A high CA125 level ( > 35 IU/mL) was significantly associated with all of the studied poor prognostic factors, except grade. The risk of lymph node metastasis (LNM) increased from 15.9% to 45.7% when CA125 level was > 35 IU/mL (p < 0.05). The optimal cut-off value for the prediction of LNM in patients aged > 50 years was determined to be 16 IU/mL (sensitivity, specificity, positive predictive value, and negative predictive value were 71%, 60%, 35%, and 87%, respectively.) Conclusions: Preoperative CA125 level was significantly related with the extent of the disease and LNM. The age-dependent cut-off level of CA125 can improve the prediction of LNM in endometrioid-type EC. For older patients, CA125 level of > 16 IU/ml could be used to predict LNM. However, further studies are needed to evaluate the appropriate cut-off level of CA125 for younger patients.

Pretreatment values of bilirubin and albumin are not prognostic predictors in patients with advanced pancreatic cancer.

PurposeTo identify the pretreatment values of bilirubin and albumin and other serum biomarkers in predicting the prognosis for advanced pancreatic cancer.MethodsA total of 201 consecutive patients pathologically diagnosed as advanced pancreatic cancer were retrospectively reviewed. Tumor location, TNM classification, the level of baseline total bilirubin (TBIT), direct bilirubin (DBIT), albumin (ALB), globulin (GLOB), total protein (TP), ALB to GLOB ratio (AGR), CA19‐9, CA242, and CA50 were collected. The values of CA19‐9, CA242, and CA50 were divided into two groups according to the upper limit value which were 1000 U/mL, 150 IU/mL, and 500 IU/mL, respectively. The values of TBIL, DBIL, IBIL, ALB, GLOB, TP, ALB, and GLOB were divided into low and high groups according to the median. To investigate if the median was an effective discriminator in dividing these markers, the patients were divided into a test set (n = 100) and a validation set (n = 101). Kaplan‐Meier (K‐M) survival analysis and Cox regression analysis were performed to explore the potential relationship between them and overall survival (OS).ResultsA K‐M survival analysis revealed that the investigated markers in test set, including TBIL, DBIL, IBIL, ALB, GLOB, TP, ALB, and GLOB, were not associated with the OS. The findings from the validation set were consistent with those in the test set. Factors with P value smaller than 0.1 in the univariate analysis along with the tumor location, CA19‐9, CA242, CA50, were entered into the multivariate analysis. A Cox regression analysis suggested that the cancerization at head of pancreas (P = 0.01) and a high level of CA19‐9 (P = 0.02) were independent prognostic indicators for poor OS of pancreatic cancer.ConclusionsBaseline bilirubin and serum proteins were not associated with the prognosis of advanced pancreatic cancer. Tumor location and level of CA19‐9 may serve as significant indicators for poor prognosis in those patients.

Cancer antigen-125 and outcomes in acute heart failure: a systematic review and meta-analysis

BackgroundCarbohydrate antigen-125 (CA125) is an ovarian cancer marker, but recent work has examined its role in risk stratification in heart failure. A recent meta-analysis examined its prognostic value in heart...

MiR-29a, targeting caveolin 2 expression, is responsible for limitation of pancreatic cancer metastasis in patients with normal level of serum CA125.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive gastrointestinal tumors, with an overall 5-year survival rate less than 8%. The dismal prognosis is mainly due to aggressive potential for metastasis. Hence, there is an urgent need for a better understanding of the molecular mechanisms underlying pancreatic cancer invasion and metastasis to improve the unfavorable overall survival (OS) of PDAC patients. In this study, we identified microRNA-29a (miR-29a) as an important tumor suppressor, which was downregulated in PDAC tissues. Moreover, miR-29a counteracted MUC16-mediated migration and invasion. In the pancreatic cancer cells, MUC16 upregulated c-Myc expression, which enhanced c-Myc binding to E-box in the miR-29a promoter and inhibited miR-29a transcription. Thus, miR-29a was negatively correlated with both MUC16 expression and serum CA125 levels. Furthermore, caveolin 2 (CAV2) was demonstrated to be the target of miR-29a by bioinformatics and luciferase reporter assays, and high CAV2 expression was responsible for a poor prognosis, especially in the subgroup with normal CA125 levels. Thus, the present study explains why high levels of serum CA125 are correlated with PDAC metastasis, highlighting the predictive value of this marker in PDAC patients.

Relationship between expressions of OCT-4, CD117 and clinicopathological features and prognosis of patients with ovarian cancer

Objective To investigate the relationship between expressions of OCT-4, CD117 and clinicopathological features and prognosis of patients with ovarian cancer. Methods A total of 70 paraffin-embedded tissues of patients with ovarian cancer from January 2010 to February 2016 in Shanxi Provincial Cancer Hospital were collected. The expressions of OCT-4 and CD117 were detected by immunohistochemistry. Results OCT-4 was mainly expressed in cytoplasm, while CD117 was expressed in cell membrane and cytoplasm. The positive expression rate of OCT-4 was 74.3% (52/70), and the positive expression rate of CD117 was 68.6% (48/70). The positive expression rates of OCT-4 in ovarian cancer tissues with poorly differentiation and high CA125 levels (≥500 U/ml), no peritoneal effusion and sensitive to chemotherapy drugs were 92.1% (35/38), 87.5% (28/32), 88.9% (24/27), and 78.7% (48/61), respectively, which were higher than those in ovarian cancer tissues with well and moderately differentiation, low CA125 levels (<500 U/ml), peritoneal effusion and resistance to chemotherapy drugs, the differences were statistically significant (P values were 0.000, 0.020, 0.047, and 0.043). The positive expression rates of CD117 in ovarian cancer tissues with poorly differentiation and peritoneal effusion were 84.2% (32/38) and 79.1% (34/43), respectively, which were higher than those in ovarian cancer tissues with well and moderately differentiation and no peritoneal effusion, the differences were statistically significant (P values were 0.006 and 0.017). Patients with OCT-4-positive expression, peritoneal effusion, and poorly differentiation had a shorter overall survival time (all P < 0.05). The peritoneal effusion and differentiation were independent prognostic factors in patients with ovarian cancer (both P < 0.05). Conclusion OCT-4 can be used as an important reference for predicting drug sensitivity and evaluating prognosis in patients with ovarian cancer. Key words: Ovarian neoplasms; OCT-4; CD117; Immunohistochemistry; Prognosis

Sulfatase 1 expression in pancreatic cancer and its correlation with clinicopathological features and postoperative prognosis

Recent studies have shown that Sulfatase 1 (SULF1) plays a crucial role in the genesis, development, and progression of tumors. However, there have been few studies on the role of SULF1 in pancreatic cancer. The present study examined the differences in SULF1 expression levels between pancreatic cancer and normal tissues, and their correlation with the clinicopathological features and prognosis. A total of 65 pancreatic cancer samples were enrolled in this study. An immunohistochemical assay were used in this study. The relationship between SULF1 expression and clinicopathological features were tested using χ2 test or Fisher's exact test. The Kaplan-Meier method was used to calculate the cumulative survival rates of the patients. The study showed that the SULF1 expression level was higher in pancreatic cancer tissues than in normal tissues. Analysis of the clinical and pathological data of patients revealed that high SULF1 expression was associated with later T, N, and TNM stages, higher CA19-9 levels, smaller tumor size, and poorer prognosis. These findings suggested that SULF1 could be an indicator of the clinicopathological features and prognosis of pancreatic cancer.