abstract: Different Levels of Sialyl-Tn Antigen Expressed on MUC16 in Patients With Endometriosis and Ovarian Cancer

Different Levels of Sialyl-Tn Antigen Expressed on MUC16 in Patients With Endometriosis and Ovarian Cancer

Abstract:

Objective:
Although CA125 antigen is a useful marker for ovarian cancer, its expression is also elevated in endometriosis. The purpose of this study was to develop an assay method for evaluating differentially glycosylated MUC16 (CA125 core protein) in patients with endometriosis and ovarian cancer.

Materials and Methods:
We prepared MUC16-enriched fractions from peritoneal fluid of patients with endometriosis and conditioned medium of ovarian carcinoma-3 cells by gel filtration, and evaluated the expression of sialyl-Lea, Tn, and sialyl-Tn antigens by dot blot analysis. A sandwich enzyme-linked immunosorbent assay was developed to measure the level of sialyl-Tn antigen expressed on MUC16 (sTn/MUC16). The level of sTn/MUC16 was compared between patients with endometriosis (n = 21) and ovarian cancer (n = 36) and in ovarian cancers with different clinical diagnostic criteria. Furthermore, distribution of MUC16 and sialyl-Tn antigen in ovarian cancer tissues was observed immunohistochemically.

Results:
Sialyl-Tn antigen was markedly detectable in the MUC16-enriched fractions from conditioned medium of ovarian carcinoma-3 cells but negligible in those from the peritoneal fluid of the patients with endometriosis. The level of sTn/MUC16 determined by a sandwich enzyme-linked immunosorbent assay was significantly higher in the patients with ovarian cancer than that in the patients with endometriosis (P < 0.001).
An elevated level of sTn/MUC16 was detected in 44% of the patients with ovarian cancer but not all the patients with endometriosis. This level increased more prominently in the patients with ovarian cancer than that of MUC16 as both the clinical stage and cytological grade advanced. An elevated level of sTn/MUC16 was frequently found in the patients with serous and endometrioid carcinomas. Consistent with this, sialyl-Tn antigen was colocalized with MUC16 in serous and endometrioid ovarian cancer tissues.

Conclusions:
Estimation of the sTn/MUC16 level may be useful for discriminating endometriosis from ovarian cancer and for evaluating the clinical stage, cytological grade, and histological type of ovarian cancer.

open access: TB Peritonitis Mistaken for Ovarian Carcinomatosis Based on an Elevated CA-125

Discussion

"In this patient, the delay in the diagnosis of tuberculous pertitonitis resulted in what may have been unnecessary radical resection of her reproductive organs. This was unfortunate as peritoneal TB is felt to be medically manageable with the standard four-drug antituberculous regimen for 6 months with the expectation that symptoms will start improving after the first week of therapy [2, 6]. If surgery is indicated, delayed surgery following medical management significantly reduces complications [3]........This case outlines the unfortunate consequences of the misdiagnosis of what probably was an antibiotic responsive illness, resulting in an unnecessarily aggressive surgical procedure."

also:

Two Cases of Ascites. - The Hong Kong Society for Infectious ...

www.hksid.org/pdf/twocasesofascites.pdf -

abstract: Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Objective

To evaluate the predictive power of serum CA-125 changes in the management of patients under going neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).

Methods

Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained.

Results

One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749 U/mL and 161 U/mL, respectively.

Comparing patients with NRD (no residual disease)  v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL, p = 0.1).

There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL (p = 0.001).

In the NRD group, 38 patients (80%) had preoperative CA-125 ≤ 100 U/mL compared to 33 patients (63.4%) in the OMD group (p = 0.04).

Conclusions

 Patients who undergo NACT-IDS (neoadjuvant chemotherapy followed by interval debulking surgery) achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤ 100 U/mL were highly likely to be cytoreduced to no residual disease.

Highlights

► Patients with advanced ovarian cancer treated with neoadjuvant chemotherapy have high rates of optimal cytoreduction.
► Preoperative CA-125 < 100 may indicate a high probability of debulking to no gross residual disease.
► A drop of > 80% in CA-125 during neoadjuvant treatment may suggest platinum sensitive disease.

(still) recruting: Official Title: Use of the CA 125 Algorithm for the Early Detection of Ovarian Cancer in Low Risk Women - ClinicalTrials.gov

Early Detection of Ovarian Cancer - Official Title: Use of the CA 125 Algorithm for the Early Detection of Ovarian Cancer in Low Risk Women

This study is currently recruiting participants.

Verified January 2012 by M.D. Anderson Cancer Center

First Received on October 3, 2007. Last Updated on January 13, 2012 History of Changes

Vignette-Based Study of Ovarian Cancer Screening: Do U.S. Physicians Report Adhering to Evidence-Based Recommendations?

Abstract

"Background: No professional society or group recommends routine ovarian cancer screening, yet physicians' enthusiasm for several cancer screening tests before benefit has been proven suggests that some women may be exposed to potential harms.

Objective: To provide nationally representative estimates of physicians' reported nonadherence to recommendations against ovarian cancer screening.

Design: Cross-sectional survey of physicians offering women's primary care. The 12-page questionnaire contained a woman's annual examination vignette and questions about offers or orders for transvaginal ultrasonography (TVU) and cancer antigen 125 (CA-125).........."

How the CA-125 became a $50,000 blood test (blog) including public/professional responses

How the CA-125 became a $50,000 blood test

abstract: Physician Knowledge and Awareness of CA-125 as a Screen for Ovarian Cancer in the Asymptomatic, Average-Risk Population - CDC study

Physician Knowledge and Awareness of CA-125 as a Screen for

Abstract

Effective early detection strategies for ovarian cancer do not exist. 

Current screening guidelines recommend against routine screening using CA-125 alone or in combination with transvaginal ultrasonography (TVS). 

In this study, the authors used the 2008 DocStyles survey to measure clinician beliefs about the effectiveness of CA-125 and TVS in the asymptomatic, average-risk population in the United States. 

To assess the need for provider education, the authors used the 2008 HealthStyles survey to examine public awareness of CA-125. 

Of 1,250 physician respondents, 40.4% said both CA-125 and TVS were effective screens, and 28.3% said neither was an effective ovarian cancer screen in the asymptomatic, average-risk population. 

Obstetrician/gynecologists [OB/GYNs] more often had responses consistent with current guidelines: 56.5% of OB/GYNs, compared with 34.4% and 29.8% of family/general practitioners and internists, respectively, said neither CA-125 nor TVS was an effective screen. 

Almost one third of women (patients/the public) surveyed reported having heard of CA-125, and about one tenth said they had the CA-125 test. 

These findings support the need for additional provider education. Educational efforts should include lack of evidence for, as well as the potential harms of, screening for ovarian cancer with CA-125.

abstract: Reference ranges for HE4 and CA125 in a large Asian population by automated assays and diagnostic performances for ovarian cancer

"The new automated HE4 assay showed good analytical and diagnostic performances. The reference limits established in our study could be used as cutoff levels to facilitate more accurate diagnosis of ovarian cancer in Asian population."

Access : CA-125 can be part of the tumour evaluation criteria in ovarian cancer trials: experience of the GCIG CALYPSO trial : British Journal of Cancer

Background:

CA-125 as a tumour progression criterion in relapsing ovarian cancer (ROC) trials remains controversial. CALYPSO is a large randomised trial incorporating CA-125 (GCIG criteria) and symptomatic deterioration in addition to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (radiological) to determine progression.

......In patients with CA-125 first progression who subsequently progressed radiologically, a delay of 2.3 months was observed between the two progression types......

Conclusion:

CA-125 and radiological tests performed similarly in determining progression with C-PLD (carboplatin-pegylated liposomal doxorubicin) or C-P (carboplatin–paclitaxel). Additional follow-up with CA-125 measurements was not associated with overtreatment.

Jan 15th: New Symptom Indices Offer No Gain in Ovarian Ca - in Oncology/Hematology, Ovarian Cancer from MedPage Today

Action Points  

---

• Explain that two new ovarian cancer symptom indices offered little advantage over the current Goff Index.



• Point out that for all three indices, sensitivity was lower for data obtained from the general practitioner's notes and highest for those interviewed over the telephone, ant that the specificity was largely unchanged

"The small differences between the three indices indicate that there is little to gain from deriving new symptom indices," the authors concluded.


"This sobering news follows hard on the heels of a large U.S. randomized trial finding no benefit, and indeed some harm, to women who were screened annually with a transvaginal ultrasound exam and a CA-125 blood test compared with a usual care control group," they wrote, referring to the NIH-sponsored Prostate, Lung, Colon, and Ovary (PLCO) screening program (JAMA 2011; 305:2295-2303).

They said one question the ovarian cancer community needs to answer is where it should focus its efforts: On the time between when a tumor is large enough to cause mild symptoms and when it is large enough to cause symptoms that prompt women to call a physician, or on a better understanding of disease etiology, leading to better prevention and therapy.

"These other research directions remain critical as the search continues for better ways to find ovarian cancer early," they said.

Primary source: Journal of the National Cancer Institute Source reference: Lim AWW, et al. "Predictive value of symptoms for ovarian cancer: Comparison of symptoms reported by questionnaire, interview, and general practitioner notes" J Natl Cancer Inst 2012; 104: 1-11. Additional source: Journal of the National Cancer Institute Source reference: Hartge P, Speyer JL. "Finding Ovarian Cancer" J Natl Cancer Inst 2012; DOI: 10.1093/jnci/drj518.

Related Article(s): ESGO: Ultrasound Allows Early Ovarian Cancer Diagnosis ESGO: Anti-CA125 Fails to Slow Ovarian Cancer SGO: Change in Antigen Predicts Ovarian Cancer Outcomes

Emergence of CA125 Immunoreactivity in Recurrent or Metastatic Primary Ovarian Mucinous Neoplasms of the Intestinal Type : eClips Consult

BLOG CA-125: What is it good for? By David Holtz, MD | January 10, 2012

Pelvic Mass Associated With Raised CA 125 For Benign Condition: A Case Report

Background:
Elevated levels of CA 125 with clinical evidence of significant weight loss and associated pelvic mass is highly suggestive of ovarian malignancy, this creates a diagnostic dilemma with the knowledge that several benign pelvic conditions may present with same findings.
Conclusion:
The presence of a pelvic mass with a raised CA 125 of 1450 units/ml, lymphadenopathy and other associated suspicious features on CT scan suggested an ovarian malignancy. A subsequent fall of CA 125 to 23 units/ml pointed to an inflammatory condition as was found intraoperatively. Raised CA 125 levels can be misleading, as illustrated in this case, a differential diagnosis of inflammatory pelvic condition should always be considered in young patients. While CT and CA 125 aids in diagnosis they should not completely supplant the need to rely on clinical history and examination findings.

Follow-up with CA125 after primary therapy of advanced ovarian cancer has major implications for treatment outcome and trial performances and should not be routinely performed

Follow-up with CA125 after primary therapy of advanced ovarian cancer: in favor of continuing to prescribe CA125 during follow-up

Search Results: ca125 - 2011 ASCO Abstracts

Search: ca125

Found 27 documents

abstract: Correlation between CA-125 serum level and response by RECIST in a phase III recurrent ovarian cancer study.

OBJECTIVES:

To evaluate in a large phase III recurrent ovarian cancer trial (OVA-301): 1) the concordance between CA-125 level vs. best overall response (OR) and progression-free survival (PFS) determined by radiological assessment 2) the impact of early CA-125 changes over the subsequent radiological response, and 3) the prognostic value of CA-125 response and CA-125 PFS to predict radiological response and PFS.

abstract: Early Detection of Recurrent Ovarian Cancer in Patients with Low-Level Increases in Serum CA-125 Levels by PET/CT

Abstract

Purpose: Serum CA-125 has been shown to be a sensitive tumor marker of recurrent ovarian cancer. The goal of this study was to evaluate the use of 2-[F-18]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the early detection of recurrent ovarian cancer in patients with low-level increases in serum CA-125 levels.

(media) Regina: Pilot project tracks whether lab tests ordered by RQHR doctors are necessary (CA125)

NCI Cancer Bulletin Mar 2011: Ovarian Cancer Study Raises Questions about Developing Markers for Early Detection

 IMPORTANT/Blogger's Note:  longterm ovarian cancer survivours and caregivers will recall the historical 'hype' on new early detection tests - caution advised and confirming this as per the NCI Bulletin below (LPA would be one example only)

"During the last decade, Dr. Ransohoff noted, some researchers made strong claims about potential markers for ovarian cancer based on preliminary data. And though the markers did not pan out, these claims were repeated by members of the media, raising false hopes about early detection."



"A long-awaited assessment of potential biomarkers for detecting early ovarian cancer shows that blood levels of the CA-125 protein remain the best predictor of the disease. But if there is to be any hope that screening will reduce deaths from this disease, then more accurate markers would have to be developed, researchers concluded in the March Cancer Prevention Research.         (note: also see blog postings for related abstracts)

None of the 28 potential serum markers tested in the study outperformed CA-125. But for screening, the researchers noted, doctors would need a test that could detect a signal from tumors more than 6 months before diagnosis; CA-125 had its strongest signal within 6 months of diagnosis.

Although the results may seem disappointing, the findings can inform future efforts to detect the disease early, the study authors wrote. This idea was echoed by several biomarker experts who were not involved in the work but who stressed the importance of the findings......."cont'd