Elevated Serum Cancer Antigen Research Articles

Pseudo-Meigs syndrome caused by a rapidly enlarging hydropic leiomyoma with elevated CA125 levels mimicking ovarian malignancy: a case report and literature review

Pseudo-Meigs syndrome is a rare syndrome characterized by hydrothorax and ascites associated with pelvic masses, and patients occasionally present with elevated serum cancer antigen-125 (CA125) levels. Hydropic leiomyoma (HLM) is an uncommon subtype of uterine leiomyoma characterized by hydropic degeneration and secondary cystic changes. Rapidly enlarging HLMs accompanied by hydrothorax, ascites, and elevated CA125 levels may be misdiagnosed as malignant tumors. Here, we report a case of HLM in a 45-year-old Chinese woman who presented with ascites and hydrothorax. Preoperative abdominopelvic CT revealed a giant solid mass in the fundus uteri measuring 20 × 15 × 12 cm. Her serum CA125 level was elevated to 247.7 U/ml, while her hydrothorax CA125 level was 304.60 U/ml. The patient was initially diagnosed with uterine malignancy and underwent total abdominal hysterectomy and adhesiolysis. Pathological examination confirmed the presence of a uterine hydropic leiomyoma with cystic changes. After tumor removal, the ascites and hydrothorax subsided quickly, with no evidence of recurrence. The patient’s serum CA125 level decreased to 116.90 U/mL on Day 7 and 5.6 U/mL on Day 40 postsurgery. Follow-up data were obtained at 6 months, 1 year, and 2 years after surgery, and no recurrence of ascites or hydrothorax was observed. This case highlights the importance of accurate diagnosis and appropriate management of HLM to achieve successful outcomes.

19 Phase II Trial of Ubamatamab in MUC16-Expressing SMARCB1-Deficient Renal Medullary Carcinoma and Epithelioid Sarcoma

Abstract Background Mucin 16 (MUC16) is a large integral membrane glycoprotein that is highly expressed in malignancies such as ovarian cancer but only at low abundance in epithelial cells of normal tissues. Proteolytic cleavage of cell surface MUC16 results in the shedding of its extracellular portion, known as cancer antigen 125 (CA-125), into the bloodstream and a short, membrane-associated C-terminal MUC16 domain that remains on the cell surface. Renal medullary carcinoma (RMC) and epithelioid sarcoma (ES) are aggressive SMARCB1-deficient malignancies found to have elevated serum CA-125 levels in 70-80% of cases. Our preclinical studies suggest that upregulation of MUC16 upon SMARCB1 loss is a viable and attractive tumor target for SMARCB1-deficient malignancies such as ES and RMC. Ubamatamab is a human IgG4-based anti-MUC16 x anti-CD3 bispecific antibody that specifically targets the cell surface bound C-terminal MUC16 domain and can thus induce T cell–redirected killing of tumor cells even in the presence of high concentrations of CA-125. It would thus be a rationale therapy to use in SMARCB1-deficient malignancies expressing MUC16, including those such as RMC known to downregulate MHC Class I as a resistance mechanism to conventional immunotherapy. This is because CD3-targeting bispecific antibodies such as ubamatamab replace conventional signal 1 by engaging T cells regardless of MHC class I expression. As proof of concept, a 20-year-old patient with metastatic SMARCB1-negative ES expressing high levels of serum CA-125 achieved a durable (12+ months) partial response to ubamatamab after progressing on multiple prior therapies, including EZH2 inhibition with tazemetostat as well as anti-PD1/CTLA4 immune checkpoint inhibition with nivolumab plus ipilimumab. The patient reported Grade 2 CRS, pleural effusion, and pericardial effusion, all of which resolved without intervention1. This serves as proof-of-concept for the ability of CD3-targeted bispecifics to overcome resistance to immune checkpoint inhibition. Given this strong preclinical and clinical evidence, we have developed a phase II clinical trial of ubamatamab alone or in combination with the anti-PD1 immune-checkpoint inhibitor cemiplimab in patients with MUC16-expressing RMC and ES who have progressed on at least one line of prior therapy. Up to 20 patients will be enrolled from each disease cohort (ES and RMC) for a total of up to 40 patients. Patients enrolled in Stage I of the trial will receive ubamatamab monotherapy. Patients with disease progression on ubamatamab monotherapy during Stage I can proceed to stage II, which will evaluate the combination of ubamatamab with cemiplimab combination. The co-primary endpoints will be objective response rate (ORR) at any time during the trial and disease control rate (DCR) through 18 weeks. Secondary endpoints will include overall survival, progression-free survival, duration of response, and safety. All endpoints will be analyzed and reported separately for each disease cohort (RMC and ES), and for each Stage (ubamatamab monotherapy and combination ubamatamab with cemiplimab). The trial will utilize the time-to-event Bayesian Optimal Phase II (TOP) design, which maximizes statistical power with well-controlled type I errors. For patients with ES, the joint null hypotheses are that the objective response rate (ORR) is 15% and the disease control rate (DCR) is 26%. The regimen will be promising if either ORR is greater than 15% or DCR is greater than 26% with 69.6% power to declare this an interesting regimen if ORR is 30% and the DCR is 43%. For patients with RMC, the joint null hypotheses are that the objective response rate (ORR) is 15% and the disease control rate (DCR) is 15%. The regimen will be promising if either ORR is greater than 15% or DCR is greater than 15% with 71.4% power to declare this an interesting regimen if ORR is 30% and the DCR is 30%. Pre- and post-treatment correlative analyses will be performed in blood and tumor biopsy tissues to identify changes in specific immune cell subsets and elucidate the dynamic evolution of tumor and immune cell compartments as well as their spatial relationships following ubamatamab alone or in combination with cemiplimab. References 1 Revon-Riviere G, Chami R, Mills D, et al. Mucin 16 (cancer antigen 125) Expression in Epithelioid Sarcoma leads to Single-Patient Study with Bispecific T-Cell Engager Ubamatamab (Mucin16xCD3): A Bench-To-Bedside Experience. Connective Tissue Oncology Society, Nov 16–19, 2022, Vancouver, Canada.

A phase 1/2 study of ubamatamab (REGN4018), a MUC16×CD3 bispecific antibody, administered alone or in combination with cemiplimab (anti–PD-1) in patients with recurrent ovarian cancer or MUC16+ endometrial cancer.

TPS5632 Background: Mucin 16 (MUC16) is a cell surface glycoprotein that is overexpressed in ovarian cancer (OC) and endometrial cancer (EC). Ubamatamab is a MUC16 × cluster of differentiation 3 (MUC16×CD3) bispecific antibody that bridges MUC16 on tumor cells and CD3 on T cells to promote T-cell–mediated cytotoxicity. Cemiplimab, a monoclonal antibody targeting the programmed cell death-1 (PD-1) receptor, enhanced MUC16×CD3 activity in preclinical models. In Phase 1 of this first-in-human study (NCT03564340), ubamatamab alone and in combination with cemiplimab demonstrated an acceptable safety profile, durable clinical activity across a range of doses, and linear pharmacokinetics (PK) in patients (pts) with recurrent OC (Liu et al. IGCS 2023. Plenary 03). Phase 2 will assess the efficacy of ubamatamab alone and in combination with cemiplimab in pts with recurrent OC. Ubamatamab will also be evaluated for recurrent advanced or metastatic EC that is MUC16+. Methods: For individuals with recurrent OC, elevated serum cancer antigen (CA)-125 ≥2× the upper limit of normal, and up to four prior lines of cytotoxic therapy, weekly dosing of ubamatamab alone or in combination with cemiplimab will be evaluated in monotherapy and combination therapy expansion cohorts. A Phase 2 cohort will also be randomized 1:1:1 to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W or ubamatamab 250 mg IV Q3W + cemiplimab 350 mg IV Q3W. For the EC cohort (≥25% of tumor cells MUC16+, as assessed by immunohistochemistry [IHC]) pts with advanced or metastatic EC that has progressed or is recurrent after prior anti–PD-1 therapy and prior platinum-based chemotherapy will be enrolled. The initial EC cohort will receive ubamatamab 250 mg IV Q3W. Based upon observed safety and activity, additional cohorts may be enrolled to receive ubamatamab 800 mg IV Q3W and/or ubamatamab 250 mg IV Q3W + cemiplimab 350 mg IV Q3W. To limit the risk of cytokine release syndrome, all pts will receive ubamatamab once-weekly step-up dosing prior to addition of cemiplimab and/or Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with an interim analysis after the first 20 pts. Any treatment arm with ≥3 objective responses may be expanded to 50 pts. In Phase 2, the primary endpoint will be the objective response rate for each arm (RECIST v1.1). Secondary endpoints include duration of response and progression-free survival, safety, PK, and change from baseline in quality of life. Exploratory objectives include clinical correlation with serum CA-125, MUC16 IHC, and immune markers. The study is currently enrolling to these OC and EC expansion cohorts. Clinical trial information: NCT03564340 .

Clinical analysis of 12 cases of ovarian yolk sac tumor

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Metastasis of cervical cancer indicated by elevation of serum CA125 produced by mediastinal lymph nodes: a case report

BackgroundIn patient assessment for recurrence of neoplasia, a biomarker that shows an elevated serum value before the first treatment is a candidate for follow-up examination. The biomarker squamous cell carcinoma antigen is usually utilized for follow-up of squamous cell cancer of the cervix.Case presentationWe herein report a 30-year-old Japanese woman of postoperative metastasis of cervical squamous cell cancer to the mediastinal and supraclavicular lymph nodes as indicated by an elevated serum cancer antigen 125 concentration and not by the squamous cell carcinoma antigen value. After chemoradiotherapy and chemotherapy, the serum cancer antigen 125 concentration decreased to a normal value. Squamous cell carcinoma antigen was found to be distributed in both the squamous cell cancer tissue of the cervix and the supraclavicular lymph node metastatic tissue. By contrast, cancer antigen 125 was distributed in the supraclavicular lymph node metastatic tissue but not in the original squamous cell cancer tissue of the cervix.ConclusionIn this case, metastasis of cervical cancer to the mediastinal and supraclavicular lymph nodes was shown by the biomarker cancer antigen 125, which was not present in the original neoplasia.

First-in-human phase 1/2 study of ubamatamab, a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab in patients with recurrent ovarian cancer.

TPS5624 Background: Mucin-16 is a cell surface glycoprotein that is overexpressed in epithelial ovarian cancer (OC). Ubamatamab (REGN4018) is a mucin-16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that promotes T cell–mediated cytotoxicity by facilitating contact between cancer cells and T cells. In mouse model studies, ubamatamab demonstrated dose-dependent antitumor activity against MUC16-expressing OC tumor cells.1 Cemiplimab is an anti–programmed cell death-1 monoclonal antibody. In a Phase 1 study (NCT03564340) in patients with recurrent OC, ubamatamab monotherapy demonstrated an acceptable safety profile, durable clinical activity across a range of doses between 20 mg and 800 mg intravenous (IV) weekly (as measured by RECIST and cancer antigen 125 [CA-125] response rates), and linear pharmacokinetics up to 800 mg IV weekly.2 These clinical data support further evaluation of a once every 3-week (Q3W) regimen of ubamatamab alone and in combination with cemiplimab. The study is currently recruiting patients to combination dose escalation, monotherapy dose expansion, and the randomized Phase 2 cohort. Methods: In Phase 2, up to 150 patients with advanced platinum-resistant OC and elevated serum cancer antigen-125 will be randomized to three arms (1:1:1) to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W as monotherapy, or ubamatamab 250 mg IV Q3W in combination with cemiplimab 350 mg Q3W. All arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome prior to proceeding to Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with an interim analysis after the first 20 patients. Any arm with ≥3 objective responses will be expanded to 50 patients. The primary objective of the dose expansion phase is to assess the preliminary efficacy of ubamatamab as monotherapy or in combination with cemiplimab, separately by cohort. Secondary objectives include characterization of the safety profile by cohort, and the pharmacokinetics of ubamatamab alone or in combination with cemiplimab, as well as patient-reported outcomes for all cohorts. In this dose expansion phase the primary endpoint will be the objective response rate for each arm as defined by RECIST 1.1 criteria. Secondary endpoints include evaluation of duration of response and progression-free survival as well as further evaluation of safety and pharmacokinetics. Exploratory endpoints include evaluation of baseline tumor MUC16 immunohistochemistry expression and other biomarkers as predictors of response. The impact of ubamatamab on quality of life and physical functioning will also be assessed.

High ATP6V1B1 expression is associated with poor prognosis and platinum‑based chemotherapy resistance in epithelial ovarian cancer.

The vacuolar ATPase H+ transporting V1 subunit B1 (ATP6V1B1) belongs to the family of ATP6Vs, which functions to transport hydrogen ions. The expression of ATP6V1B1 and associated clinicopathological features have been linked to various cancers; however, its role in epithelial ovarian cancer (EOC) has remained to be explored. The present study aimed to unveil the function, molecular mechanisms and clinical significance of ATP6V1B1 in EOC. The mRNA levels of ATP6V1 subunits A, B1 and B2 in EOC tissues were determined using data from the Gene Expression Profiling Interactive Analysis database and RNA sequencing. Protein levels of ATP6V1B1 were evaluated through immunohistochemistry staining of EOC, borderline, benign and normal epithelial tissues. The association between ATP6V1B1 expression and clinicopathological features and prognosis of patients with EOC was analyzed. Furthermore, the biological role of ATP6V1B1 in ovarian cancer cell lines was also assessed. RNA sequencing and public dataset analyses revealed elevated ATP6V1B1 mRNA levels in EOCs. High ATP6V1B1 protein levels were also observed in EOC compared with those of borderline and benign tumors and nonadjacent normal epithelial tissues. High ATP6V1B1 expression was associated with the serous cell type, advanced International Federation of Gynecology and Obstetrics stage, high/advanced tumor grade, elevated serum cancer antigen 125 levels and platinum resistance (P<0.001, P<0.001, P=0.035, P=0.029 and P=0.011, respectively). High expression levels of ATP6V1B1 were also associated with poor overall and disease‑free survival (P<0.001). Knockdown of ATP6V1B1 decreased cancer cell proliferation and colony‑forming abilities (P<0.001) invitro by inducing cell cycle arrest in G0/G1 phase. Significant upregulation of ATP6V1B1 was observed in EOC and the prognostic significance and association with chemotherapy resistance of ATP6V1B1 in EOC was demonstrated, rendering it an EOC‑related biomarker for prognostic evaluation and chemotherapy resistance, as well as a potential therapeutic target for patients with EOC.

Endometrioid carcinoma associated with ovarian endometriosis: need for cautions during treatment

Although endometriosis could be associated with certain epithelial ovarian cancers and elevated serum cancer antigen (CA) 19-9 levels, it is difficult to diagnose endometriosis using this marker. We report an unusual case of endometriosis that evolved into endometrioid carcinoma in an asymptomatic 38-year-old woman with elevated CA 19-9 levels who presented to our clinic. Transvaginal ultrasound and computed tomography of the abdomen and pelvis revealed endometriosis of the right ovary. A laparoscopy was performed to evaluate for chocolate cysts. However, based on the postoperative pathological assessment, she was diagnosed with endometrioid carcinoma associated with endometriosis and was reoperated for surgical staging. This case indicates that sudden elevation of CA 19-9 level might be a sign of malignancy, small asymptomatic endometriosis should not be ignored, and incidental diagnosis of ovarian cancer should be carefully assessed by surgical staging.

The Potential Role of MUC16 (CA125) Biomarker in Lung Cancer: A Magic Biomarker but with Adversity.

Lung cancer is the second most commonly diagnosed cancer in the world. In terms of the diagnosis of lung cancer, combination carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) detection had higher sensitivity, specificity, and diagnostic odds ratios than CEA detection alone. Most individuals with elevated serum CA125 levels had lung cancer that was either in stage 3 or stage 4. Serum CA125 levels were similarly elevated in lung cancer patients who also had pleural effusions or ascites. Furthermore, there is strong evidence that human lung cancer produces CA125 in vitro, which suggests that other clinical illnesses outside of ovarian cancer could also be responsible for the rise of CA125. MUC16 (CA125) is a natural killer cell inhibitor. As a screening test for lung and ovarian cancer diagnosis and prognosis in the early stages, CA125 has been widely used as a marker in three different clinical settings. MUC16 mRNA levels in lung cancer are increased regardless of gender. As well, increased expression of mutated MUC16 enhances lung cancer cells proliferation and growth. Additionally, the CA125 serum level is thought to be a key indicator for lung cancer metastasis to the liver. Further, CA125 could be a useful biomarker in other cancer types diagnoses like ovarian, breast, and pancreatic cancers. One of the important limitations of CA125 as a first step in such a screening technique is that up to 20% of ovarian tumors lack antigen expression. Each of the 10 possible serum markers was expressed in 29-100% of ovarian tumors with minimal or no CA125 expression. Therefore, there is a controversy regarding CA125 in the diagnosis and prognosis of lung cancer and other cancer types. In this state, preclinical and clinical studies are warranted to elucidate the clinical benefit of CA125 in the diagnosis and prognosis of lung cancer.

Costochondral gout

We present a case of a 37-year-old Caucasian woman with abdominal distension and loss of weight. She was initially presumed to be a case of ovarian malignancy due to an elevated serum cancer antigen 125 (CA 125) level and imaging of abdomen and pelvis that showed ascites and bulky ovaries. However, histological examination of biopsy later revealed it to be a case of abdominal tuberculosis (AbT). Ascitic fluid was also found to be positive for <i>Mycobacterium tuberculosis</i> by whole genome sequencing. The patient was started on antituberculosis treatment following which she showed a significant improvement in her symptoms.

Relationship between the serum cancer antigen 125 level and the weight of surgically enucleated adenomyosis

Elevated serum levels of cancer antigen 125 (CA125) are known to occur in adenomyosis. However, the relationship between the severity of adenomyosis and serum CA125 levels has not yet been elucidated. The present study aimed to examine the correlation between the weight of adenomyosis and the serum CA125 level. This retrospective study, after applying exclusion criteria, investigated 308 patients who underwent conservative surgery for adenomyosis. Serum CA125 levels were measured before surgery and weights of surgically enucleated adenomyosis were measured in the operating room. Both serum CA125 and surgically enucleated adenomyosis weight showed log-normal distributions. Pearson’s product-moment correlation coefficient for the logarithmically converted values was 0.617 (95% confidence interval, 0.54–0.68). The serum CA125 level correlated positively with the weight of adenomyosis. Although the qualitative characteristics and clinical significance of adenomyosis lesions remain unclear, it seems that the investigation of the relative relationship between the serum CA125 level and the size of the affected lesion is useful to observe one of the qualitative features of adenomyosis. Furthermore, the present study supports the use of postoperative serum CA125 levels as an important indicator for determining the therapeutic effects of conservative surgical treatment for adenomyosis and detecting early signs of recurrence. Impact Statement What is already known on this subject? Elevated serum cancer antigen 125 (CA125) levels are known to occur in adenomyosis and are widely recognised as helpful in the diagnosis of adenomyosis. What do the results of this study add? There is a positive correlation between the serum CA125 level and the weight of adenomyosis. What are the implications of these findings for clinical practice and/or further research? The postoperative serum CA125 level is an important indicator for evaluating the extent of the affected lesion remaining after conservative surgical treatment for adenomyosis and also helpful for detecting early signs of recurrence. Further study is required to examine whether it is possible to clarify the qualitative characteristics of adenomyosis in each different case based on the CA125-producing ability of the lesion.

Dramatically Elevated Serum Cancer Antigen 19-9 due to an Epidermoid Cyst in the Pouch of Douglas

A 30-year-old nullipara was admitted to our hospital for presenting with a pelvic mass with dramatically elevated serum cancer antigen 19-9 (CA 19-9) of 9355.12U/mL. The transvaginal ultrasound and pelvic magnetic resonance imaging indicated a dumbbell-shaped cyst on left ovary (Fig. 1A). An exploratory laparoscopy was performed and revealed a full-round cyst near the left ovary located in the pouch of Douglas (Fig. 1B), and an adhesion zone on the peritoneum with a normal uterus and bilateral polycystic ovaries were found (Fig.

Recurrent Right-side Pleural Section Effusion Mimicking Malignancy: Pseudo-Meig’s Syndrome

Pseudo-Meig’s syndrome is an unusual presentation in which a benign ovarian tumour develops with ascites and pleural effusion. Diagnosis of exclusion is made only after ovarian fibroma has been ruled out and confirmed by disappearance of pleural effusion. The present case report is of a 55-year-old female, who presented with progressive shortness of breath, on and off right chest pain, and abdominal distension, over a period of 2-3 months. Clinical examination and a chest radiograph confirmed pleural effusion as the cause of progressive dyspnea. Presence of a pelvic mass and an elevated serum Cancer Antigen-125 (CA-125) increased the probability of malignancy. After complete tumour resection, a pathological report confirmed a benign ovarian tumour. The authors highlight the importance of suspicion, careful general examination, radiological evaluation, and histologic examination to confirm the diagnosis of pseudo-Meig’s syndrome.

Postoperative transient elevation of serum cancer antigen 125 in non-small cell lung cancer patients.

The aim of this retrospective study was to investigate the correlation of transiently elevated postoperative serum cancer antigen 125 levels and prognosis in patients with non-small cell lung cancer. A total of 181 non-small cell lung cancer patients with normal levels of preoperative serum cancer antigen 125 were statistically summarized in this study. Out of the analyzed patients, 22 (12.2%) showed elevation of serum cancer antigen 125 within one month after surgery. Serum cancer antigen 125 level decreased to normal at three months postoperation. Serum cancer antigen 125 was positively correlated with pro-brain natriuretic peptide in non-small cell lung cancer postoperative patients (p=0.00035). Univariate analysis did not find significant difference in disease progression survival between those who experienced cancer antigen 125 elevation in the early postoperation and those who did not (p=0.646). In conclusion, transient elevation of cancer antigen 125 is associated to pro-brain natriuretic peptide increase after pulmonary surgery in non-small cell lung cancer patients.

Inflammatory signals induce MUC16 expression in ovarian cancer cells via NF-κB activation.

Cancer antigen 125 (CA125), encoded by the mucin 16 cell surface associated (MUC16) gene, has been widely used as a biomarker for ovarian cancer (OC) screening. However, it has yet to be elucidated as to why its levels increase with tumor progression as well as with certain other non-malignant conditions. Based on our knowledge of the inflammatory microenvironment (IME) in OC, HEY cells were treated with several inflammation-associated factors as well as their antagonists, and it was observed that inflammation-associated factors upregulated MUC16 gene expression. Considering the role of nuclear factor (NF)-κB in the inflammatory signaling network and our previous research on OC, chromatin immunoprecipitation was performed, and it was observed that activated NF-κB bound to the MUC16 gene promoter and enhanced its expression, thereby elevating secreted CA125 levels. These findings demonstrated that IME and MUC16 gene expression were associated in OC, partly elucidating the role of IME in tumor progression, explaining the elevated serum CA125 levels in some non-malignant conditions, and confirming IME as a potential target for OC therapy.

Immunohistochemical Study of CA 125 in Surface Epithelial Tumors of Ovary in Correlation with Serum Levels

Background:&#x0D; Ovarian carcinoma is the 4th leading cancer among women in India. Primary ovarian neoplasms exhibit a wide range of histopathological patterns and tumors with epithelial differentiation are most frequent. Among malignant tumors, most common histological type is serous adenocarcinoma whose diagnosis is established in advanced stages of disease in approximately 75% of patients.&#x0D; The most widely used tumor marker in ovarian cancer, often considered “gold standard” is Cancer Antigen125. Cancer Antigen 125 is a high molecular weight glycoprotein which is raised in approximately 90% of patients with advanced epithelial ovarian cancer.&#x0D; &#x0D; Methods:&#x0D; A 2 year prospective study included 81 cases of ovarian neoplasms with surface epithelial differentiation. The specimens were fixed in 10% formalin, routinely processed. Sections of 4-5 microns thickness were obtained from the paraffin block and stained with Hematoxylin &amp; Eosin. The tumors were categorised according to WHO classification. Immunohistochemical analysis of Cancer Antigen 125 was done in all malignant &amp; borderline tumors.&#x0D; &#x0D; Result:&#x0D; A total of 81 cases were studied. There were 15 cases with elevated serum Cancer Antigen 125 levels. Of these 8 showed positive tissue expression. The sensitivity of serum Cancer Antigen 125 was 68.75% &amp; its specificity was 93.8%.&#x0D; &#x0D; Conclusion: &#x0D; Serum Cancer Antigen 125 is elevated in ovarian tumors especially in malignant surface epithelial tumors &amp; more commonly in serous cystadenocarcinoma. There was a good correlation between serum levels &amp; tissue expression of Cancer Antigen 125.

Ovarian Burkitt’s Lymphoma in a Four-Year-Old Girl: A Rare Case

Burkitt’s Lymphoma (BL) is one of the most common paediatric cancers in Sub-Saharan Africa. It is a high-grade lymphoma associated with Epstein Barr Virus (EBV) and malaria infections as co-factors. It may occur as an abdominal tumour with ovarian involvement in a few cases. Previous incidences range between 0.5% to 1.5% of all ovarian neoplasm and are involved in 19% of all adnexal lymphomas. Its occurrence is often among those aged between 6-62 years but very rare among four-year-old girls. This study describes a case of ovarian BL in a four-year-old girl presenting with difficulty in breathing, abdominal pain and distension. The lymphoma had spread to several sites within a short duration. This case represents a great challenge in paediatric oncology management as to when medical or surgical treatment should be considered. Significant laboratory findings were elevated serum Cancer Antigen (CA) 125 and Lactate Dehydrogenase (LDH). Furthermore, flow cytometry, histopathology and immunohistochemistry were confirmed as BL. The child completed chemotherapy and is on remission. Despite its rarity in children, this tumour should be treated aggressively to improve long-term survival.

Association between cancer antigen 19-9 and diabetes risk: A prospective and Mendelian randomization study.

Aims/IntroductionElevated serum cancer antigen 19‐9 (CA19‐9) levels have been found in diabetes patients in most observational studies; however, whether there is a causal association between CA19‐9 and diabetes mellitus is unclear.Materials and MethodsOur study was carried out based on the Dongfeng‐Tongji cohort comprising 27,009 individuals. We first investigated the associations between serum CA19‐9 levels and incident diabetes mellitus risk in a prospective cohort study (12,700 individuals). Then, we explored the potential causal relationship between CA19‐9 and diabetes mellitus risk in a cross‐sectional study (3,349 diabetes mellitus patients and 8,341 controls) using Mendelian randomization analysis. A weighted genetic risk score was calculated by adding the CA19‐9 increasing alleles in five single‐nucleotide polymorphisms (rs17271883, rs3760776 and rs3760775 in FUT6, rs11880333 in CA11, rs265548 in B3GNT3, and rs1047781 in FUT2), which were identified in a previous genome‐wide association study on serum CA19‐9 levels.ResultsIn the prospective study, a total of 1,004 incident diabetes mellitus patients were diagnosed during a mean 4.54‐year follow‐up period. Elevated serum CA19‐9 level was associated with a higher incident diabetes risk after adjustment for confounders, with a hazard ratio of 1.20 (95% confidence interval 1.11–1.30) per standard deviation (12.17 U/mL) CA19‐9 increase. Using the genetic score to estimate the unconfounded effect, we did not find a causal association of CA19‐9 with diabetes risk (odds ratio per weighted CA19‐9‐increasing allele: 0.99, 95% confidence interval 0.94–1.04; P = 0.61).ConclusionsThe present study did not support a causal association of serum CA19‐9 with diabetes risk. CA19‐9 might be a potential biomarker of incident diabetes mellitus risk.

The role of adjuvant radiotherapy in stage I endometrial cancer: A single-institution outcome

ObjectivePostoperative radiotherapy for early endometrial cancer has been investigated in several randomized trials. These trials demonstrate that it reduces loco-regional recurrence, but has no impact on overall survival. The aims of this study were to better understand the role of adjuvant radiotherapy and determine predictors for loco-regional recurrence or development of distant metastasis. Materials and methodsA retrospective medical records review was performed on patients with surgical stage I endometrial cancer treated at Taipei Veterans General Hospital between 2006 and 2013. Multivariable analysis was conducted using Cox regression for prognostic predictors. ResultsA total of 337 patients were identified. The estimated five-year overall survival and loco-regional recurrence-free survival were 96.3% and 97.9% in the non-radiotherapy group, and 91.6% and 97.1% in the radiotherapy group (p = 0.06 overall survival, p = 0.956 loco-regional recurrence-free survival). Multivariable analysis revealed that elevated preoperative serum Cancer Antigen 125 (CA-125) level (hazard ratio (HR) = 2.54), age older than 60 years old (HR = 3.34), and depth of myometrial invasion > 50% (HR = 3.37) were significant factors in overall survival. Elevated preoperative CA-125 level (HR = 5.37), age older than 60 years (HR = 6.57), positive lymphovascular space invasion (HR = 50.20), and adjuvant radiotherapy (HR = 0.05) were independent predictors of loco-regional recurrence-free survival. For distant metastasis, deep myometrial invasion was a significant risk factor. ConclusionsPostoperative radiotherapy delivery is an independent predictor for loco-regional recurrence-free survival but has no impact on overall survival in this population. Preoperative CA-125 level is a risk factor for loco-regional recurrence, and deep myometrial invasion was correlated with distant metastasis.

Stroke in malignancy: complexities of diagnosis and management: a case report

BackgroundAlthough there is an established association between cancer and stroke, the role of malignancy as a causative agent or comorbidity is not always clear. Moreover, there are no established guidelines on the acute treatment of cancer-associated stroke or optimal anticoagulation. This case report illustrates the significance of these practice gaps.Case presentationA 62-year-old Caucasian woman presented to our institute with acute neurological deficits and was found to have an occluded left middle cerebral artery on a computed tomographic angiogram. She was administered intravenous alteplase and underwent unsuccessful endovascular clot retrieval. Besides smoking and her age, she had no cerebrovascular risk factors, and the results of baseline investigations for the cause of stroke were negative. Subsequent computed tomography of the chest, abdomen, and pelvis showed metastatic malignancy, and in the context of a significantly elevated serum cancer antigen 19-9, we suspected a pancreatic primary cancer. A transthoracic echocardiogram demonstrated mitral regurgitation but no visible vegetation. The patient died of her illness. We made a diagnosis of cancer-associated stroke, specifically a likely case of nonbacterial thrombotic endocarditis.ConclusionsThis case highlights the importance of having a high threshold of suspicion for malignancy as a cause of stroke.