Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125.

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.

Development of an ovarian cancer symptom index: possibilities for earlier detection.

BACKGROUND: Currently, screening for ovarian cancer is not recommended for the general population. Targeting women with specific symptoms for screening has been evaluated only recently, because it was believed that symptoms had limited specificity. METHODS: A case-control study of 149 women with ovarian cancer, including 255 women who were in a screening program and 233 women who were referred for pelvic/abdominal ultrasound, was conducted by inviting women to complete a survey of symptoms. Patients were divided randomly into an exploratory group and a confirmatory group. Symptom types, frequency, severity, and duration were compared between cases and controls. Logistic regression analyses were used to determine which factors independently predicted cancer in the exploratory group and then were used to develop a symptom index, which was tested for sensitivity and specificity in the confirmatory group. RESULTS: Symptoms that were associated significantly with ovarian cancer were pelvic/abdominal pain, urinary urgency/frequency, increased abdominal size/bloating, and difficulty eating/feeling full when they were present for <1 year and occurred >12 days per month. In a logistic regression analysis, symptoms that were associated independently with cancer were pelvic/abdominal pain (P < .001), increased abdominal size/bloating (P<.001), and difficulty eating/feeling full (P = .010). A symptom index was considered positive if any of those 6 symptoms occurred >12 times per month but were present for <1 year. In the confirmatory sample, the index had a sensitivity of 56.7 for early-stage disease and 79.5% for advanced-stage disease. Specificity was 90% for women age >50 years and 86.7% for women age <50 years. CONCLUSIONS: Specific symptoms in conjunction with their frequency and duration were useful in identifying women with ovarian cancer. A symptom index may be useful for identifying women who are at risk.