A Pilot Study May Offer Promise of a Marker for Ovarian Cancer

New Orleans, LA -- Each year, there are more than 27,000 new cases of ovarian cancer and 14,000 deaths due to this deadly disease. Sadly, preventative measures cannot help decrease these numbers in ovarian cancer because there are no symptoms in early-stage disease, no lack of readily recognizable and detectable precursor lesions, and the no specific and sensitive screening tests. Consequently, in more than 75 percent of patients with epithelial carcinoma of the ovary, retroperitoneal or intra-abdominal spread is present at diagnosis.

The atrial natriuretic peptide (ANP) influences the tone and caliber of blood vessels and has a potential role in modulating volume homeostasis, i.e. the state of equilibrium in the body with respect to various functions and to the chemical compositions of the fluids and tissues. ANP is secreted by atrial myocytes as a 126 aminoacid molecule and divided into different fragments, namely proANP(1-30) (NtANP), proANP(31-67) (mdANP), proANP(79-98) and the active ANP(99-126).

Similar properties have been reported in previous research studies for ANP and proANP-(1-30). A University of South Florida research finding demonstrated that plasma ANP levels in gynecologic cancer patients were significantly higher than those in healthy, non-pregnant women. Now, physiologists from the same institution have attempted to extend their original observations on ANP in gynecologic malignancy, in particular to examine the possible relationship between ANP and proANP-(1-30) levels in plasma and ascites fluid (serous fluid from the peritoneal cacity) in primary cancer of the ovaries.

The authors of a new study entitled, “Atrial Natriuretic Peptide (ANP) and proANP-(1-30) levels in Gynecologic Malignancy," are Papineni S. Rao, PhD, Richard J. Cardosi, MD, John R. Dietz, PhD, James V. Fiorica, MD, Edward C. Grendys, jr, MD, and Mitchel S. Hoffman, MD, from the Departments of Obstetrics & Gynecology and Physiology & Biophysics, University of South Florida, and H.Lee Moffit Cancer Center & Research Institute, Tampa, FL. Dr. Rao will present their findings in detail at the American Physiological Society’s (APS) annual meeting, part of the "Experimental Biology 2002--Translating the Genome,” conference. More than l2,000 attendees are attending the conference which is being held April 20-24, 2002 at the Ernest N. Morial Convention Center, New Orleans, LA.

Methodology

Fourteen women undergoing primary cytoreductive surgery for ovarian carcinoma participated in this study following informed consent. On the day of surgery, blood samples were obtained prior to the induction of anesthesia and ascites was collected intraoperatively. Following centrifugation the samples were divided into equal parts and stored at -70 degrees C until tested. The extraction of ANP and proANP-(1-30) from the plasma and ascites was accomplished by reverse phase C-8 micro columns using standard methods. The eluted fraction was dried and reconstituted in tested buffer ANP and proANP- (1-30) levels were measured by radioimmunoassay according to previously published methods.

This confirms previous findings that plasma ANP levels in women with primary cancer of the ovaries are significantly higher than the values reported for normal healthy women.

The researchers found little or no information with reference to proANP- (1-30) levels as it pertains to malignancy.

They did discover that the measured levels of plasma ANP (34.9 +/- 5.5 pg/ml) are significantly higher than the levels in ascites fluid (12.8 +/- 2.7 pg/ml). A similar trend was observed for proANP-(1-30) with the plasma values of 368 +/- 54 vs. 227 +/- 34 pg/ml for ascites.

Conclusions

This pilot study is the first to demonstrate the correlation between ANP and proANP- (1-30) in both the serum and ascites in women with epithelial ovarian cancer. Malignant ascites associated with ovarian cancer is an exudate, or fluid out of a tissue resulting from injury. Therefore, it is plausible that the presence of these substances in ascites is simply related to leaky vascular network. However, these research findings demonstrated a significant difference in the plasma and ascites concentrations suggesting that other mechanisms may be involved. Tumor cells may synthesize and secrete these peptides as was shown to be true for ANP in small cell lung cancer. In addition, differences may exist in the binding capacity of ANP or proANP-(1-30) to proteins in the plasma vs: ascites.

Accordingly, the researchers suggest further investigation into ANP and proANP- (1-30) and their role in the biological development of malignant ascites in women with epithelial ovarian cancer. A better understanding of the cause of these conditions may lead to improved palliative management of malignant ascites.

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