Does HE4 have a role in the recurrence of ovarian cancer? | 2012 ASCO Annual Meeting Abstracts (+ links to related ovarian abstracts)

Does HE4 have a role in the recurrence of ovarian cancer? | 2012 ASCO Annual Meeting Abstracts

Abstract:
Background: Human epididymis protein 4 (HE4) has been recently described as a new marker for early ovarian cancer, with higher sensitivity (76.9%) compared to CA125. This is the third study in literature on the role of HE4 in recurrence of ovarian cancer and the first evaluating the sensitivity of HE4 and CA125 in these patients  

Methods: Plasma was obtained 24 hours before secondary cytoreductive surgery from consecutive patients with suspicious recurrence ovarian cancer operated from November 2010 to April 2011 at University Campus Bio-Medico of Rome. CA125 levels were evaluated by a one-step "sandwich" radioimmunoassay. HE4 levels were determined using the HE4 enzymatic immune assay. The CA125 cut-off was less than 35 U/mL. Two cut-off were considered for HE4: less than 150 pmol/L (according to the manufacturer's indications) and less than 70 pmol/L.  

Results: Fourteen patients were histologically confirmed as recurrence ovarian cancer. Mean Ca125 plasma concentration was 31.95 ± 22.09 U/mL (range 1.1 – 64.3). Mean HE4 plasma concentration was 225.83± 286.82 pmol/L (range 21.61- 633.6). The sensitivity of CA125 was 35.7 %. The sensitivity of HE4 was 71.4% and 28.6% above the cut-off of 70 pmol/L and 150 pmol/L, respectively. The dual marker combination of CA125 and HE4 at 70 pmol/L cut-off yielded the highest sensitivity (85.7%) to detect recurrence ovarian cancer.  

Conclusions: Even if a standard cut-off point has not been determined, this study suggested that HE4 may potentially be a more sensible marker for recurrence ovarian cancer than CA125 and the association between CA125 and HE4 at cut-off of 70 pmol/L seems to yield the highest sensitivity.

  Other Abstracts in this Sub-Category:

	1. Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: A GCIG and EORTC-GCG study. Meeting: 2012 ASCO Annual Meeting Abstract No: LBA5000 First Author: Ignace B. Vergote Category: Gynecologic Cancer - Ovarian Cancer
	2. Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): A randomized, open-label phase II study. Meeting: 2012 ASCO Annual Meeting Abstract No: 5001 First Author: Amit M. Oza Category: Gynecologic Cancer - Ovarian Cancer
	3. AURELIA: A randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC). Meeting: 2012 ASCO Annual Meeting Abstract No: LBA5002^ First Author: Eric Pujade-Lauraine Category: Gynecologic Cancer - Ovarian Cancer
	More...

paywalled: CT diagnosis of intrasplenic metastasis from ovarian carcinoma

CT diagnosis of intrasplenic metastasis from ovarian carcinoma

 We concluded that CT can demonstrate intraparenchymal and infiltrative splenic metastasis in patients with ovarian cancer even in the absence of increased CA 125 levels.

paywalled: Two-marker Combinations for Preoperative Discrimination of Benign and Malignant Ovarian Masses

Two-marker Combinations for Preoperative Discrimination of Benign and Malignant Ovarian Masses

Abstract

Background: 

When caring for patients with ovarian neoplasms, correct preoperative discrimination of benign and malignant disease is deemed vital. In this study, we tested serum biomarkers' alone and in combination, to achieve this aim.

Conclusion: 

A combination of CA-125 with HE4 could facilitate the identification of women at risk for ovarian cancer.

paywalled: Mucin 16 (cancer antigen 125) expression in human tissues and cell lines and correlation with clinical outcome in adenocarcinomas of the pancreas, esophagus, stomach, and colon

Mucin 16 (cancer antigen 125) expression in human... [Hum Pathol. 2012] - PubMed - NCBI

Hum Pathol. 2012 Apr 26

Mucin 16 (cancer antigen 125) expression in human tissues and cell lines and correlation with clinical outcome in adenocarcinomas of the pancreas, esophagus, stomach, and colon

Abstract

Mucin 16 (cancer antigen 125) is a cell surface glycoprotein that plays a role in promoting cancer cell growth in ovarian cancer. The aims of this study were to examine mucin 16 expression in a large number of digestive tract adenocarcinomas and precursors and to determine whether mucin 16 up-regulation is correlated with patient outcome.

Tissue microarrays were constructed using surgical resection tissues and included pancreatic (115 normal, 29 precursors, 200 pancreatic ductal adenocarcinomas), esophageal (86 normal, 104 precursors, 95 esophageal adenocarcinomas, 35 lymph node metastases), gastric (211 normal, 8 precursors, 119 gastric adenocarcinomas, 62 lymph node metastases), and colorectal (34 normal, 17 precursors, 39 colorectal adenocarcinomas) tissues. Mucin 16 was detected in 81.5%, 69.9%, 41.2%, and 64.1% of the pancreatic ductal adenocarcinomas, esophageal adenocarcinomas, gastric adenocarcinomas, and colorectal adenocarcinomas, respectively. Mucin 16 was seen in a subset of the precursors. On multivariate analysis, moderate/diffuse mucin 16 in pancreatic ductal adenocarcinomas was strongly associated with poor survival (P < .001), independent of other prognosis predictors. A similar trend was observed for esophageal adenocarcinomas (P = .160) and gastric adenocarcinomas (P = .080). Focal mucin 16 in colorectal adenocarcinomas was significantly correlated (P = .044) with a better patient outcome, when compared with mucin 16-negative cases. Using Western blot analysis, we found mucin 16 expression in 3 of 6 pancreatic ductal adenocarcinoma and 1 of 2 esophageal adenocarcinoma cell lines.

We conclude that most of the digestive tract adenocarcinomas and a subset of their precursors express mucin 16. Mucin 16 expression is an independent predictor of poor outcome in pancreatic ductal adenocarcinomas and potentially in esophageal adenocarcinomas and gastric adenocarcinomas. We propose that mucin 16 may function as a prognostic marker and therapeutic target in the future.

paywalled: Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.

Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.

Abstract

The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77 %, HE4 85 %, and CA72.4 72 %. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p < 0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55 % of the patients, increased values of CA125 and HE4 in 65 % of the patients, and finally increased HE4 and CA72.4 in 75 % of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p < 0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.

abstract: Preoperative Identification of a Suspicious Adnexal Mass: A Systematic Review and Meta-analysis. PET/MRI/U/S

 Blogger's Note: this abstract provides little comprehensive information (as per most abstracts)  noting that the journal of Gynecologic Oncology is a subscriber-based journal ($$$); 'nail in the coffin'  for ovarian cancer/pre-surgical assessment ??
                    ~~~~~~~~~~~~~~~~~~~

abstract: Preoperative Identification of a Suspicious Adnexal Mass: A Systematic Review and Meta-analysis [Gynecol Oncol. 2012] - PubMed - NCBI

Abstract

OBJECTIVE:

To systematically review the existing literature in order to determine the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer.

METHODS:

A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of a 2004 AHRQ systematic review on the topic, searches of MEDLINE for studies published since 2004 was also conducted to update and supplement the evidentiary base. A bivariate, random-effects meta-regression model was used to produce summary estimates of sensitivity and specificity and to plot summary ROC curves with 95% confidence regions.

RESULTS:

Four meta-analyses and 53 primary studies were included in this review. The diagnostic performance of each technology was compared and contrasted based on the summary data on sensitivity and specificity obtained from the meta-analysis. Results suggest that 3D ultrasonography has both a higher sensitivity and specificity when compared to 2D ultrasound. Established morphological scoring systems also performed with respectable sensitivity and specificity, each with equivalent diagnostic competence. Explicit scoring systems did not perform as well as other diagnostic testing methods. Assessment of an adnexal mass by colour Doppler technology was neither as sensitive nor as specific as simple ultrasonography. Of the three imaging modalities considered, MRI appeared to perform the best, although results were not statistically different from CT. PET did not perform as well as either MRI or CT. The measurement of the CA-125 tumour marker appears to be less reliable than do other available assessment methods.

CONCLUSION:

The best available evidence was collected and included in this rigorous systematic review and meta-analysis. The abundant evidentiary base provided the context and direction for the diagnosis of early-staged ovarian cancer.

Abstract - Biotargets of Cancer in Current Clinical Practice - Ovarian Cancer

 Medicine

Biotargets of Cancer in Current Clinical Practice

Current Clinical Pathology, 2012, 381-401, DOI: 10.1007/978-1-61779-615-9_14

Abstract -
  
Abstract

Ovarian cancer is the fifth most common cancer in women and is the most lethal of all gynecologic cancers. Early-stage ovarian cancer is curable while women who are diagnosed with advanced ovarian cancer continue to have poor long-term survival due to recurrence of disease. Unfortunately, most women are diagnosed with advanced-stage disease. Early detection is a primary objective for clinicians and scientists, yet single modality (CA-125, transvaginal ultrasound) screening tests have been ineffective. More recent novel approaches combining modalities and utilizing serial serum sampling are being tested and hold great promise. In addition, the recent application of proteomics to this clinical question has the potential to identify new and important biotargets.

Unfortunately, the majority of ovarian cancer patients have advanced-stage disease, and although most will die of their disease, their survival is quite heterogenous (different). 

The ability to stratify patients according to prognosis could help guide therapy. The current “gold standard” for prognosis uses patient, surgical, and tumor characteristics, yet these have the tendency to be notoriously inaccurate. This prognostic uncertainty and the drive to identify predictive factors by which we can select novel and targeted therapy have stimulated researchers to look beyond traditional markers and test and validate molecular and genomic biomarkers, which are anticipated to soon complement or even eclipse traditional factors clarifying prognosis and select treatments. 

For patients with advanced-stage disease, a multitude of prognostic factors have been characterized. While promising, none of these biotargets have been validated at present to be clinically useful. More recent application of genomic technologies is likely to yield clinically relevant signatures and/or biotargets which will provide the basis for personalization of care for these patients.

abstract: Adnexal masses in women with breast cancer

Adnexal masses in women with breast cancer:

Background

Adnexal masses detected in breast cancer survivors are of particular concern because of the increased risk of ovarian malignancy.

Aims

This study was performed to analyse adnexal masses among women with breast cancer with regard to variables predictive of malignancy.

Methods

The study included women with breast cancer who had undergone surgery for an adnexal mass between 2002 and 2010 at Hacettepe University Hospital. A total of 45 consecutive women with a mean age of 47.3 years (range 25–76) were analysed retrospectively.

Results

Of 45 cases reviewed, benign ovarian pathology was found in 35 cases (77.8%) and malignant ovarian neoplasms were found in 10 cases (22.2%). A simple ovarian cyst was observed in 25 cases (71.4%) as the most common type of benign pathology. Of the 10 cases with malignancy, 5 (50%) had primary ovarian carcinoma, while the remaining five women had breast carcinoma metastases to the ovary. Complex mass at ultrasonography, increased CA 125 level and oestrogen receptor–negative tumour were found to be the significant predictors of ovarian malignancy.

Conclusions

Although an adnexal mass in a woman with breast cancer is most commonly a benign ovarian cyst, the overall risk of ovarian malignancy is increased with breast cancer. An adnexal mass with complex architecture detected by ultrasonography and high CA 125 level were the strongest risk factors associated with increased risk of malignancy.

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

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 undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).


Conclusions 
Patients who undergo NACT-IDS 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 ≤100U/mL were highly likely to be cytoreduced to no residual disease.

abstract: Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders

Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders: Publication year: 2012


Objective
The human epididymis protein 4 (HE4) is a novel biomarker for ovarian cancer. This study measured the HE4 and CA125 levels in women with benign gynecological disorders. 

Study Design 
Sera were obtained from women prior to surgery for a pelvic mass and HE4 and CA125 levels were determined. The proportions of patients with elevated biomarker levels were compared.

Results 
There were 1042 women with benign disease. HE4 levels were less often elevated than CA125 (8% vs 29%) . A marked difference was observed in patients with endometriosis in which HE4 was elevated in 3% of patients and CA125 in 67% . Serous ovarian tumors were associated with elevated levels of HE4 in 8% of patients and CA125 in 20%; uterine fibroids in 8% vs 26% ; dermoids in 1% vs 21% ; and inflammatory disease in 10% vs 37% .

Conclusion
HE4 is elevated less frequently than CA125 in benign disease, particularly in premenopausal patients.

March 22, 2012: Journal of Ovarian Research | open access | The value of serum CA125 for the development of virtual follow-up strategies for patients with epithelial ovarian cancer: A retrospective study

Blogger's Note: past studies also confirm the connection between doubling of CA125/nadir, focus on remote care/followup

Journal of Ovarian Research | Abstract | The value of serum CA125 for the development of virtual follow-up strategies for patients with epithelial ovarian cancer: A retrospective study

Research

"Current NCCN guidelines for the follow up of patients with EOC are widely accepted but only limited evidence is available to support current clinical practice [3]. There are no clinical trials available to determine optimal follow up intervals, sequence or duration of follow up."

The value of serum CA125 for the development of virtual follow-up strategies for patients with epithelial ovarian cancer: A retrospective study

Journal of Ovarian Research 2012, 5:11 doi:10.1186/1757-2215-5-11
Published: 22 March 2012

Abstract (provisional)

Background

Serum CA125 is routinely used in the follow up of ovarian cancer. The objective of the present study was to evaluate the usefulness of CA125 in the detection of ovarian cancer recurrence.

Methods

This retrospective case study was carried out at a tertiary gynaecological cancer centre in Australia. Patients with all cell types of epithelial ovarian cancer (EOC) treated between 2003 and 2010 were considered eligible. We excluded patients whose aim of treatment was palliative, had no follow-up, had no pre-operative CA125 reading or had pre-operative CA125 levels < 35 U/mL. After primary treatment, patients were followed up as per guidelines suggested by National Comprehensive Cancer Network (NCCN). We recorded if symptoms, findings from physical examination, imaging or serum CA125 levels led to the diagnosis of recurrence. An increase in CA125 levels to twice the postoperative nadir was considered as "doubling" at any time during follow up.

Results

Analysis is based on 56 patients who completed primary treatment and who presented for a total of 274 follow-up episodes. Of those, 29 patients (52%) developed a recurrence within the follow up period. Recurrence was diagnosed by CA125 alone in 14 of 29 patients (48%). CA125 was not elevated in 7 patients (24%) who recurred. Doubling of CA125 from nadir was observed in 27/29 patients. Of those 27 patients the doubling from nadir occurred within the normal range of 35 U/ml in 3 cases and outside the normal range in 24 cases. Multivariate analysis suggests that doubling of serum CA125 (OR 5.10, p 0.036) and nadir CA125 >10 U/ml (OR 2.86, p 0.01) remained the only independent factors to predict ovarian cancer recurrence.

Conclusions

The present paper proposes the validation of a novel CA125 algorithm aiming to detect recurrent EOC. These data may allow us to investigate novel ways of follow up that do not require a patient's physical attendance at a clinic (virtual follow-up).

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

(open access journal) Journal of Ovarian Research - Struma Ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report (Iran)

Journal of Ovarian Research -  Struma Ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report

Case report

Struma Ovarii associated with Pseudo-Meig's syndrome and high serum level of CA 125; a case report

Journal of Ovarian Research 2012, 5:10 doi:10.1186/1757-2215-5-10
Published: 21 March 2012

Abstract (provisional)

Struma ovarii is a rare form of ovarian neoplasm in a form of mature teratoma and is composed predominantly of thyroid tissue. In the literature review, there has only been 10 cases of this tumor, associated with ascites and pleural effusion (Meig's Syndrome) and increased CA125 so far. In such cases, the tumor mimics malignant ovarian tumor. In this article, the case of a 72-year-old symptomatic woman with a pelvic mass, pleural and peritoneal effusion and high level of serum CA125  (607.4)  is presented. Cytological evaluation for the pleural fluid was performed. She underwent hysterectomy and bilateral salpingo-oophorectomy. The result of pathologic diagnosis is presented in this paper. The patient was well in postoperative period and paraclinical tests including CA 125 were normal as well.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

abstract: HE4 combined with MDCT imaging is a good marker in the evaluation of disease extension in advanced epithelial ovarian carcinoma.

HE4 combined with MDCT imaging is a good marker in the evaluation of disease extension in advanced epithelial ovarian carcinoma

Abstract

The purpose of the study was to evaluate the expression of the biomarkers CA125 and HE4 combined with imaging, in patients with advanced epithelial ovarian cancer (EOC). Forty-six women with EOC were included in the study all affected with peritoneal carcinomatosis. ................The availability of biomarkers, particularly HE4, together with sophisticated imaging techniques, strengthens the clinical relevance of this study, for the follow-up of patients with peritoneal carcinomatosis.

                        ~~~~~~~~~~~~~~~~~~~~~~~

carcinomatosis - definition of carcinomatosis in the Medical ...

medical-dictionary.thefreedictionary.com/carcinomatosis

carcinomatosis /car·ci·no·ma·to·sis/ (kahr″sĭ-no-mah-to´sis) the condition of widespread dissemination of cancer throughout the body.

REPOST: CA-125: To Monitor or Not to Monitor?: Evidence Against Monitoring CA-125

 Blogger's Note: Medscape requires registration (free)

CA-125: To Monitor or Not to Monitor?: Evidence Against Monitoring CA-125

 From Medscape Hematology-Oncology

CA-125: To Monitor or Not to Monitor?

For Ovarian Cancer Patients in Remission

Gordon Rustin, MD; Beth Y. Karlan, MD; Maurie Markman, MD

Authors and Disclosures

Posted: 03/08/2012

Controversies Continue in NCCN Ovarian Cancer Guidelines

Medscape Medical News from the:  

National Comprehensive Cancer Network (NCCN) 17th Annual Conference

This coverage is not sanctioned by, nor a part of, the National Comprehensive Cancer Network.

From Medscape Medical News > Conference News

Controversies Continue in NCCN Ovarian Cancer Guidelines

Neoadjuvant Chemotherapy and CA-125 Reviewed

March 20, 2012 (Hollywood, Florida) — The ovarian cancer guidelines from the National Comprehensive Cancer Network (NCCN) address a number of ongoing controversies, according to a presenter here at the NCCN 17th Annual Conference.

 

"There have not been a lot of changes in the past year, but there are various areas of controversy in the guidelines," Robert Morgan, MD, from the City of Hope Comprehensive Cancer Center in Los Angeles, California, told Medscape Medical News at the conference.
One such controversy is about the usefulness of the biomarker CA-125 to monitor patients who have been treated with surgery and/or chemotherapy. Dr. Morgan called CA-125 the "most controversial" aspect of patient follow-up.......

The Chinese-German Journal of Clinical Oncology - abstract: Clinical significance of CA125 regression in chemotherapy of advanced ovarian cancer

The Chinese-German Journal of Clinical Oncology

Abstract

Objective  

The aim of this study was to compare the serum CA125 regression in advanced ovarian carcinoma patients treated with paclitaxel/platinum (TP) and platinum/epirubicin/ifosfamide (PAC) during early chemotherapy. The relationship between survival and CA125 regression during first line chemotherapy was evaluated.

Conclusion  

There isn’t significant difference in serum CA125 regression between patients who are treated with PAC or PT during early chemotherapy. CA125 half-life and nadir CA125 concentration are independent prognostic factor in advanced ovarian cancer.

open access: Performance of a multianalyte test as an aid for the diagnosis of ovarian cancer in symptomatic women (comparison to CA-125)

Performance of a multianalyte test as an aid for the diagnosis of ovarian cancer

Performance of a multianalyte test as an aid for the diagnosis of ovarian cancer in symptomatic women

Journal of Translational Medicine 2012, 10:45 doi:10.1186/1479-5876-10-45

Publication date 12 March 2012
Article URL http://www.translational-medicine.com/content/10/1/45

"The study population comprised 244 apparently healthy normal women, 223 patients with benign gynecological conditions, 53 patients with borderline ovarian tumours and 222 patients with malignant ovarian tumours (serous, mucinous, endometrioid, clear cell, other)  (Table 1)."

"The malignant ovarian cancer cohort comprised 130 (58.5%) serous, 19 (8.6%)endometrioid, 16 (7.2%) mucinous, 16 (7.2%) clear cell and 41 (18.5%) of other types that included predominantly mixed forms and adenocarcinomas with no specific histotype recorded (Table 1). A total of 33 (14.9%) of malignant ovarian cancer samples had no staging data reported, 42 (18.9%) were diagnosed with Stage I disease, 27 (12.2%) with Stage II, 106 (47.7%) Stage III and 14 (6.3%) with Stage IV disease (Table 1)."

"Of the ovarian malignancies, 88.5% of all serous tumours, 57.9% of all endometrioid tumours, 62.5% of all mucinous tumours, 81.2% of all clear cell tumours and 85.4% of other epithelial ovarian cancer plasma samples were correctly identified (Table 5). The IVDMIA correctly predicted 91.7% of the late stage (Stages III-IV) samples, and 69.6% of the early stage (Stages I-II) malignant ovarian cancer samples (Table 5).

Conclusions
This study confirms in an independent sample set that a blood-based multianalyte assay has significant advantages over CA125 for distinguishing symptomatic women with borderline and malignant ovarian cancer from controls or those with benign disease.

Competing interests
This study was funded as part of the research and development activities of Healthlinx Ltd. DJA, LR, KK and KB are employees of Healthlinx Ltd and GER is non-executive chairman of Healthlinx Ltd. DJA is an inventor on patent applications that are related to the current
study.

Keywords
Ovarian cancer, Tumour markers, Multianalyte, Diagnostic
Background

abstract: Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125 (includes graphic/study of 23 patients)

 Highlights
(in study of 23 patients)

► Three new markers were compared to CA125 for lead time to ovarian cancer recurrence.
► HE4 elevates at recurrence when CA125 does not.
► Mesothelin has less marker potential, MMP7 shows promise and requires confirmation.
  
Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125: Publication year: 2012

Objective 
Evaluate and compare the effectiveness of CA125, HE4, Mesothelin and MMP7 marker levels to monitor ovarian cancer patients after surgery and chemotherapy. Evaluate the lead time of a rise of marker levels before recurrence.

Methods 
The study consists of 23 patients with advanced stage ovarian/fallopian tube cancer. Blood was drawn after front line surgery and chemotherapy treatment and at 3 month intervals thereafter. One patient had chemoresistant disease, two patients remained in remission and 20 patients had recurring disease and were used for marker evaluation.

Results
In five patients HE4 was the only marker to elevate before recurrence with a lead time of up to 4½ months including one patient who did not have a CA125 response at all. In a further two patients, HE4 increased before CA125 did. In four of these seven patients, HE4 levels were consistently at or above threshold during remission when both CA125 and imaging results were negative. MMP7 elevated before recurrence in one patient who was negative for the other markers. Mesothelin elevated in two patients who were also positive for CA125 and HE4.

Conclusions 
HE4 can predict ovarian cancer recurrence earlier than CA125 and it can be elevated in patients that do not express CA125 at sufficient levels to make a clinical decision. MMP7 and Mesothelin have lower potential as markers for ovarian cancer recurrence to complement CA125. A failure of HE4 levels to normalize at completion of standard therapy may indicate a poor prognosis.

Graphical Abstract

Highlights

► Three new markers were compared to CA125 for lead time to ovarian cancer recurrence.
► HE4 elevates at recurrence when CA125 does not.
► Mesothelin has less marker potential, MMP7 shows promise and requires confirmation.

open access: CA-125: To Monitor or Not to Monitor?: Evidence Against Monitoring CA-125 For Ovarian Cancer Patients in Remission (Dr's Rustin, Karlan, Markman)

CA-125: To Monitor or Not to Monitor?: Evidence Against Monitoring CA-125

 For Ovarian Cancer Patients in Remission

Gordon Rustin, MD; Beth Y. Karlan, MD; Maurie Markman, MD

Authors and Disclosures

Posted: 03/08/2012

Editor's Note:
 
CA-125 is the most useful tumor marker in ovarian cancer. Since 1981, measurement of the serum level of the CA-125 antigen has become a standard component of routine management of women with advanced ovarian cancer.^[1,2] CA-125 concentrations are used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients. However, the question remains as to whether routine monitoring of CA-125 in women with advanced ovarian cancer in complete remission is advantageous. Recently, Drs. Gordon Rustin and Beth Karlan -- experts in the treatment of ovarian cancer -- participated in a Medscape Virtual Debate via email addressing the question, "Should patients with advanced ovarian cancer in complete remission undergo routine CA-125 monitoring?" Dr. Maurie Markman served as moderator. What follows is their conversation..........cont'd

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.