Tumor Marker For Ovarian Cancer Research Articles

Validation and comparison of tumor-associated trypsin inhibitor (TATI) immunoassays

BackgroundTumor-associated trypsin inhibitor (TATI) is mainly proposed as a tumor marker for ovarian cancer. However, recent discoveries of TATI in cancer and inflammatory diseases show that assay of TATI in biological samples is of increasing interest. MethodsWe validated a previously described TR-IFMA and a newly developed dual-monoclonal sandwich ELISA for TATI. These methods were compared with a commercial radioimmunoassay (RIA). We studied preanalytical factors affecting serum TATI concentrations and established age- and gender specific reference intervals using serum samples from 195 healthy volunteers. ResultsThe assay range and precision were 0.8–45μg/L and <9.1% for the ELISA, and 0.13μg/L–150μg/L and <12.5% for the TR-IFMA, respectively. Both assays correlated well with a RIA. Type of blood sample and nutritional status were not critical and TATI was stable in serum samples when stored at +4°C and −20°C for 4weeks and at −80°C for 8weeks. The 95% reference limits for serum TATI in adults were 5.2–15.3μg/L in the age group 18–70years and 7.5–21.3μg/L in the age group >70years. ConclusionsSignificantly higher concentrations of serum TATI were observed in elderly women and in men. Both ELISA and TR-IFMA technologies can be employed to develop sensitive and robust immunoassays for TATI using monoclonal antibodies.

Expression of tumor necrosis factor-α in ovarian carcinoma ascites and its meaning

Objective To investigate the relationship of ovarian cancer and the ascites levels of TNF-a, and to determine the value of elevated TNF-a ascites level on discriminating the feature of ascites. Methods Ascites levels of TNF-a of 59 specimens of epithelial ovarian tumor, 9 specimens of peritoneal primary serous papillary carcinoma （PPSPC） and 6 specimens of endometriosis cyst were detected via ELISA. Results Ascites levels of TNF-a of patients with EOC, PPSPC, BOT were significantly higher than those with BET and EM, and they were related to the clinical stage, tissue differentiation, lymph node metastasis and volume of ascites. Conclusion Aseites levels of TNF-a have the high sensitivity and specificity for diagnosis of ovarian cancer. It might be the tumor marker of ovarian cancer. Key words: Tumor necrosis factor-or; Tumor necrosis factor receptor- I ; Enzyme linked immunosor-bent assay ; Ovarian tumor

Elevated CA 125 levels in patients with aortic stenosis: relation to clinical severity and echocardiographic parameters

Carbohydrate antigen 125 (CA 125), known as a tumor marker for ovarian cancer, has been reported to increase in relation to disease severity in heart failure patients with systolic dysfunction. Aortic stenosis (AS) has a wide clinical spectrum that often includes heart failure symptoms. The purpose of the present study is to evaluate the serum levels of CA 125 in patients with AS and its relation to clinical severity and echocardiographic parameters. The study group consisted of 42 patients (20 males, 22 females, mean age 62.5 ± 14.9 years) with AS and 35 healthy controls (17 men, 18 women; mean age 59.0 ± 9.1 years). All patients and control subjects underwent chest X-ray and echocardiographic evaluation. We measured serum CA 125 values in patients with AS and control subjects. The median (interquartile range) CA 125 level was significantly higher among AS patients than in the control group in covariate analysis (9.4 [2.5-38.1] vs. 6.8 [4.4-13.9] U/ml respectively; p=0.001). Spearman correlation analysis in the whole group indicated that CA 125 was positively correlated with aortic mean gradient (p=0.007, r=0.30) and creatinine levels (p=0.02, r=0.26). We found that CA 125 levels were elevated in patients with AS and were correlated with mean gradient and creatinine levels.

Comparison of Serum Human Epididymis Protein 4 with Cancer Antigen 125 as a Tumor Marker in Patients with Malignant and Nonmalignant Diseases

Human epididymis protein 4 (HE4), a precursor of human epididymis protein, has been proposed as a tumor marker for ovarian cancer. We evaluated HE4 in comparison with cancer antigen 125 (CA 125) in healthy individuals and in patients with benign and malignant diseases. CA 125 and HE4 serum concentrations were determined in 101 healthy individuals, 535 patients with benign pathologies (292 with benign gynecologic diseases) and 423 patients with malignant diseases (127 with ovarian cancers). CA 125 and HE4 cutoffs were 35 kU/L and 140 pmol/L, respectively. HE4 and CA 125 results were abnormal in 1.1% and 9.9% of healthy individuals and in 12.3% and 37% of patients with benign diseases, respectively. Renal failure was the most common cause of increased HE4 in patients with benign disease, who had significantly higher HE4 concentrations (P = 0.001) than patients with other benign diseases. HE4 showed a higher specificity than CA 125 in patients with benign gynecologic diseases, with abnormal concentrations in 1.3% and 33.2% of the patients, respectively. HE-4 concentrations were abnormal primarily in gynecologic cancer and lung cancer. By contrast, CA 125 was increased in many different nonovarian malignancies, including nonepithelial tumors. A significantly higher area under the ROC curve was obtained with HE4 than with CA 125 for differentiating benign from malignant diseases (0.755 vs 0.643) and in the differential diagnosis of gynecologic diseases (0.874 vs 0.722). HE4 has significantly higher diagnostic specificity than CA 125, and the combination of CA 125 and HE4 improved the detection of ovarian cancer in all stages and histological types.

Metastatic Medullary Thyroid Cancer Presenting with Elevated Levels of CA 19-9 and CA 125

Calcitonin and carcinoembryonic antigen (CEA) are established markers of medullary thyroid cancer (MTC), used in the diagnosis and monitoring of disease and its progression. In clinical practice, various other tumor markers are utilized in the follow-up of different malignancies, although their utility has not been well described in MTC. CA 19-9 antigen, routinely used in the monitoring of pancreatic cancer, also has been detected in the tissue of approximately 6% of MTCs. However, its presence has never been reported in the serum of these patients. Elevation of CA 125 antigen, utilized as a tumor marker for ovarian cancer, has never been reported in MTC. We report a novel finding of metastatic MTC presenting with elevated CA 19-9 and CA 125 serum levels, with concurrent tissue staining for these antigens. A 56-year-old woman with multiple endocrine neoplasia 2B syndrome, post subtotal thyroidectomy for MTC in childhood, presented with extensive metastatic spread of MTC to the lungs and liver, 47 years after the original diagnosis. The patient's calcitonin level decreased from 2950 to 261 pg/mL (reference range: <20 pg/mL) over a 20-year period. The serum CEA level was elevated at 6800 ng/mL (reference range: <5.1 ng/mL). Because of a concern for an alternate malignancy, serum CA 19-9 and CA 125 tumor markers were measured and found to be significantly elevated, at 39,334 U/mL (reference range: <35.1 U/mL) and 96.2 U/mL (reference range: 7-41 U/mL), respectively. Immunostaining of the metastatic MTC tissue showed patchy staining for calcitonin, strongly positive staining for CEA and CA 19-9, and weakly positive staining for CA 125. Drawing from experience with CA 19-9 and CA 125 tumor markers in other malignancies, we propose that they may be associated with aggressive forms of MTC with significant metastatic potential.

The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses

Cancer antigen 125 (CA125) is the best known single tumor marker for ovarian cancer (OC). We investigated whether the additional information of the human epididymis protein 4 (HE4) improves diagnostic accuracy. We retrospectively analyzed preoperative sera of 109 healthy women, 285 patients with benign ovarian masses (cystadenoma: n=78, leimyoma: n=66, endometriosis: n=52, functional ovarian cysts: n=79, other: n=10), 16 low malignant potential (LMP) ovarian tumors and 125 OC (stage I: 22, II: 15, III: 78, IV: 10). CA125 was analyzed using the ARCHITECT system, HE4 using the ARCHITECT(a) system and EIA(e) technology additionally. The lowest concentrations of CA125 and HE4 were observed in healthy individuals, followed by patients with benign adnexal masses and patients with LMP tumors and OC. The area under the curve (AUC) for the differential diagnosis of adnexal masses of CA125 alone was not significantly different to HE4 alone in premenopausal (CA125: 86.7, HE4(a): 82.6, HE4(e): 81.6% p>0.05) but significantly different in postmenopausal [CA125: 93.4 vs. HE4(a): 88.3 p=0.023 and vs. HE4(e): 87.8% p=0.012] patients. For stage I OC, HE4 as a single marker was superior to CA125, which was the best single marker in stage II-IV. The combination of CA125 and HE4 using risk of malignancy algorithm (ROMA) gained the highest sensitivity at 95% specificity for the differential diagnosis of adnexal masses [CA125: 70.9, HE4(a): 67.4, HE4(e): 66.0, ROMA(a): 76.6 and ROMA(e): 74.5%], especially in stage I OC [CA125: 27.3, HE4(a): 40.9, HE4(e): 40.9, ROMA(a): 45.5 and ROMA(e): 45.5%]. CA125 is still the best single marker in the diagnosis of OC. HE4 alone and even more the combined analysis of CA125 and HE4 using ROMA improve the diagnostic accuracy of adnexal masses, especially in early OC.

Expressions of osteopontin and B7-H4 in epithelial ovarian neoplasm and their significance

Epithelial ovarian cancer involves a number of factors. Recent studies have shown that osteopontin (OPN) is related to the occurrence and development of a variety of tumors, but few studies are on ovarian cancer. B7-H4 is a newly identified tumor marker in ovarian cancer. This study explored the expression of OPN and B7-H4 and their clinical significance in epithelial ovarian tumors. The expression of OPN and B7-H4 in 15 cases of normal ovarian tissue, 20 of benign ovarian tumor tissue, 20 of borderline ovarian tumor tissue, and 40 of ovarian cancer tissue were detected by immunohistochemistry, and the relationship of OPN and B7-H4 expression to clinical and pathologic features of ovarian cancer was analyzed. The expression of OPN and B7-H4 were significantly higher in ovarian cancer than in borderline and benign tumors (P<0.05). The positive rates of OPN and B7-H4 were significantly higher in poorly differentiated ovarian cancer than in medium and highly differentiated ovarian cancer (P<0.05), and the levels of expression were significantly lower in tissue at stages I and III of ovarian cancer than in stages III and IV (P<0.05). The positive rate of OPN associated with a higher rate of lymph node metastasis (P<0.05), but did not relate to age and histologic type. The positive rate of B7-H4 were significantly higher in ovarian serous carcinoma than in the mucinous carcinoma (P<0.05), but did not relate to age and lymph node metastasis. The expression of OPN and B7-H4 increased in epithelial ovarian cancer, which could be referenced in the diagnosis of ovarian malignant tumors.

The relationship between the expression of hK6 in ovarian neoplasm and the clinicopathologic variables and prognosis

Objective The aim of this study was to approach the relationship between the expression of human kallikrein 6 (hK6) in ovarian neoplasm and the clinicopathologic variables and prognosis for finding a new tumor marker for ovarian cancer.

Heterologous immunization, a way out of the problem of monoclonal antibody production against carcinoma antigen 125.

Monoclonal antibodies (mAbs) are essential tools for many molecular immunology investigations, epitope mapping and molecular modelling, clinical laboratory diagnostic tests and immunotherapy. Humoral immune response of immunized animals largely depends on the nature of antigen and the immunization technique. Polysaccharides and heavily-glycosylated proteins are very elusive targets incapable of mounting long-lasting, high affinity antibody responses. Carcinoma antigen 125 (CA 125), a well known tumor marker of ovarian cancer, is a mucin type antigen consisting of repetitive units of heavily glycosylated moieties which render production of mAbs very difficult. To evaluate the efficacy of heterologous antigen preparations as a way of mouse immunization in the production of anti-CA 125 mAb. Two different protocols of immunization were used for priming of NMRI mice. In the first method, mice conventionally immunized by three intraperitoneal injections of purified CA 125 and boosted by the antigen three days before fusion. In the second approach, mice were primed by three intraperitoneal injections of living CA 125 positive cells of OVCAR-3 cell line, and boosted by intravenous injection of the purified extracellular domain of CA 125. Production of mAb was performed by standard hybridoma technology and mAbs were characterized by different immunoassays. The first method failed to produce stable clones despite six time fusion. A total of ten stable clones, however, were produced in the second approach. Some of the clones were characterized and found to have excellent immunoreactivity when tested by ELISA assay, western blotting, intracellular and surface immunofluorescent staining of OVCAR-3 cell line and immunohistochemical staining of ovarian cancer tissues. Altogether the results of the present study clearly showed that heterologous antigen preparation is the method of choice for immunization when production of monoclonal antibody against highly glycosylated poorly immunogenic antigens is concerned.

Prostasin, A Potential Tumor Marker in Ovarian Cancer- A Pilot Study

INTRODUCTION:Ovarian cancer is generally diagnosed at advanced stages of the disease; therefore, poor prognoses are typical. The development of tumor markers is thus of utmost importance. Prostasin is a protease that in normal tissues is highly expressed only in the prostate gland and seminal fluid. A previous study showed that prostasin is highly overexpressed in ovarian cancer cell lines. This study sought to evaluate the expression of prostasin in ovarian cancer.METHODS:Fresh tumor samples of ovarian epithelial cancer (n: 12) were analyzed for expression of prostasin mRNA (messenger ribonucleic acid) by conventional and real time quantitative PCR (polymerase chain reaction). As a standard control, a normal prostate sample was analyzed.RESULTS:Using conventional PCR, prostasin was detected in all but one sample. Using quantitative PCR, prostasin was over-expressed in all but one of the samples as compared to the control (prostate).CONCLUSIONS:These findings indicate that prostasin is overexpressed in many epithelial ovarian cancers. Further studies of prostasin as a potential biomarker for this disease are warranted.

Afamin and Apolipoprotein A-IV: Novel Protein Markers for Ovarian Cancer

Comparative proteomics identified the vitamin E-binding plasma protein afamin as a potential novel tumor marker for ovarian cancer. In addition, we observed in a previous small study decreased plasma concentrations of apolipoprotein A-IV (apoA-IV) in preoperative patients with kidney cancer. The aim of this study was therefore to analyze afamin and apoA-IV in a large case-control study to evaluate the diagnostic utility of the two potential novel tumor markers in ovarian cancer patients. We measured plasma concentrations of afamin and apoA-IV by means of a specific sandwich-type ELISA using affinity-purified polyclonal and monoclonal antibodies in 181 ovarian cancer patients of various clinical stages, 399 patients with benign gynecologic diseases, including endometriosis, and 177 controls and compared results with those for the conventional ovarian cancer tumor marker cancer antigen 125 (CA125). Afamin concentrations decreased from a median of 70.7 mg/L (range, 34.6-116.1 mg/L) in healthy controls to 65.2 mg/L (range, 20.2-206.6 mg/L) in patients with benign gynecologic diseases to 56.0 mg/L (range, 4.7-96.0 mg/L) in ovarian cancer patients (P < 0.001 for all pairwise comparisons). Similar results were obtained with apoA-IV concentrations decreasing from 13.0 mg/dL (range, 5.5-34.0 mg/dL) in controls to 11.7 mg/dL (range, 2.0-32.3 mg/dL) in benign conditions to 9.4 mg/dL (range, 0.3-29.5 mg/dL) in ovarian cancer (all P < 0.001). Receiver operating characteristic analysis for differentiating ovarian cancer patients from healthy controls revealed for a specificity of 90% sensitivity values of 92.4%, 42.4%, and 40.8% for CA125, afamin, and apoA-IV, respectively. Afamin, but not apoA-IV, added independent diagnostic information to CA125 and age for differentiating ovarian cancer from benign and healthy samples; the odds ratio of ovarian cancer was reduced by 44% for each doubling of afamin (P = 0.032). The relatively low sensitivity, however, clearly indicates that afamin and apoA-IV alone are not sufficiently suitable as diagnostic markers for ovarian cancer. Afamin contributes, however, independent diagnostic information to CA125, thus establishing its potential as an adjunct marker to CA125.

β1,3-Galactosyltransferases-4/5 Are Novel Tumor Markers for Gynecological Cancers

Background/Aims: While the CA 125 and SCC antigens are used as tumor markers for ovarian cancer and uterine cervical cancer, respectively, an effective marker for uterine corpus cancer has not been identified. We asked whether β1,3-galactosyltransferase-4 and/or 5 (β3Gal-T4/T5) could serve as novel tumor markers for detecting gynecological carcinomas, especially those of the uterine corpus. Methods: We obtained a monoclonal antibody and a polyclonal antiserum against β3Gal-T5 and constructed a sandwich ELISA method. Western blot analysis and immunoprecipitation revealed that this ELISA recognizes both β3Gal-T4 and β3Gal-T5. Results: We found β3Gal-T4 and T5 enzymatic activity in ovarian cancer tissues, indicating that these enzymes are expressed at least in ovarian cancer. The cutoff value was determined by ROC analysis to be 5.4 ng/ml in the sera. The β3Gal-T4/T5-positive rates for the sera from ovarian cancer and uterine cervical cancer patients were comparable with the CA 125- and SCC antigen-positive rates for these cancers, respectively. Significantly, the β3Gal-T4/T5-positive rate was higher for uterine corpus cancer (64%) than the CA 125 (37%)- and CA 19-9 (24%)-positive rates. The stage I uterine corpus cancers had particularly high β3Gal-T4/T5-positive rates (57%). Conclusion: β3Gal-T4/T5 is a novel tumor marker for uterine corpus cancer and other gynecological cancers.

Role of CA125 in predicting ovarian cancer survival - a review of the epidemiological literature

CA125 is the gold standard tumor marker in ovarian cancer. Serum level of CA125 is used to monitor response to chemotherapy, relapse, and disease progression in ovarian cancer patients. Thus, it is reasonable to investigate whether CA125 may have utility as a prognostic indicator as well in ovarian cancer. A large number of epidemiological studies have been carried out to this effect. This review summarizes all available epidemiological literature on the association between CA125 levels and survival in ovarian cancer. To place these studies in context, we provide some background information on CA125 and its role in ovarian cancer.

Differential Methylation Profile of Ovarian Cancer in Tissues and Plasma

An accurate biomarker for detection of ovarian cancer may reduce cancer-related mortality. Using a previously developed microarray-based technique, we evaluated differences in DNA methylation profiles in a panel of 56 genes using sections of serous papillary adenocarcinomas and uninvolved ovaries (n=30) from women in a high-risk group. Methylation profiles were also generated for circulating DNA from blood of patients (n=33) and healthy controls (n=33). Using the most differentially methylated genes for naïve Bayesian analysis, we identified ten of these profiles as potentially informative in tissues. Various combinations of these genes produced 69% sensitivity and 70% specificity for cancer detection as estimated under a stratified, fivefold cross-validation protocol. In plasma, five genes were identified as informative; their combination had 85% sensitivity and 61% specificity for cancer detection. These results suggest that differential methylation profiling in heterogeneous samples has the potential to identify components of a composite biomarker that may detect ovarian cancer in blood with significant accuracy.

Proteomics identification of stress-induced phosphoprotein (STIP1) as a potential biomarker for human ovarian cancer

16533 Patients with ovarian cancers are often associated with poor prognosis and limited survival rates because their cancers were not detected at earlier stages. Currently, CA125 is the most commonly used tumor marker for ovarian cancer, but it only results in 78% sensitivity, 82 to 95% specificity, and 82% positive predictive value. Therefore, discovery of new tumor markers for detecting ovarian cancer is warranted. Peripheral blood is a convenient source of tumor markers. However, screening for new tumor markers from blood is difficult because tumor markers, usually at low concentrations in blood, are easily obscured by serum abundant common proteins. Alternatively, tumor interstitial fluid (TIF) represents a rich source for secreted proteins from both cancer cells and neighboring stromal tissues, and the contents of TIF are eventually drained into blood circulation. In this study, we attempted to identify cancer-specific proteins from TIF derived from human ovarian cancer with proteomics approaches. Using statistical analysis of 596 protein spots in two-dimensional gels between the TIF of ovarian cancer and normal interstitial fluid (NIF) of normal ovaries, we identified several differentially expressed proteins, including stress-induced phosphoprotein 1 (STIP1). Specific elevations of STIP1 in TIF and ovarian cancer tissues were confirmed with Western blot analysis and immunohistochemistry, respectively. Subsequent enzyme-linked immunosorbent assay (ELISA) experiments revealed serum levels of STIP1 were significantly higher in ovarian cancer patients than in healthy controls. Receiver operating characteristics (ROC) curve analysis suggested the value of STIP1 to be comparable to CA125. These results suggest STIP1 has the potential as a biomarker for human ovarian cancer. No significant financial relationships to disclose.

The use and understanding of CA125 as a tumor marker for ovarian cancer: a questionnaire-based survey

The aim of this study was to assess the level of understanding of the role of the tumor marker CA125 in ovarian cancer among doctors of different grades specializing in obstetrics and gynecology (O&G), medicine, surgery, and primary care (general practitioners [GPs]). The study involves a questionnaire-based survey. Two hundred and fifty-nine questionnaires were distributed. An overall response rate of 47.1% was achieved. All grades of doctors and all major specialties were represented. There was a significant difference in the level of self-reported CA125 ordering between the medical specialties, O&G being the most frequent users and primary care the least (P < 0.001), and between the grade of doctors, senior house officers/preregistration house officers and GPs less than consultants and middle grade doctors (P < 0.001). Electronic literature was the first source of advice for the majority of respondents (38.5%). The knowledge of false-positive causes for a raised CA125 was low in medicine, surgery, and primary care specialties, as was the awareness of the sensitivity and specificity of CA125 in epithelial and nonepithelial ovarian cancers. The role of CA125 in ovarian cancer is poorly understood, especially among doctors working outside O&G. Guidelines should be developed to aid clinicians from all specialties in the most appropriate application of CA125 in their practice. Substantial cost savings could be made by the introduction of clear protocol-driven ordering in an attempt to reduce the number of inappropriate tests performed.

Biomarker Discovery in Ovarian Cancer

Ovarian cancer is a leading cause of gynecologic cancer death among women. Tumors diagnosed early (in stage I) have a cure rate approaching 90%. However, because specific symptoms and screening tools are lacking, most ovarian cancers are very advanced when finally diagnosed. CA125 expression and pelvic ultrasonography are of limited efficacy in screening, and the search for new, complementary ovarian cancer biomarkers continues. New technology and research techniques have allowed the identification of over 100 possible tumor markers, many of which are still being evaluated for clinical relevance and several of which have entered clinical trials. Here, we review the methods of biomarker discovery, address the significance and functions of newly identified ovarian cancer tumor markers, and provide further insight into the future of ovarian cancer biomarkers.

Combining multiple serum tumor markers improves detection of stage I epithelial ovarian cancer

Objective. Currently available tumor markers for ovarian cancer are still inadequate in both sensitivity and specificity to be used for population-based screening. Artificial neural network (ANN) as a modeling tool has demonstrated its ability to assimilate information from multiple sources and to detect subtle and complex patterns. In this paper, an ANN model was evaluated for its performance in detecting early stage epithelial ovarian cancer using multiple serum markers. Methods. Serum specimens collected at four institutions in the US, the Netherlands and the United Kingdom were analyzed for CA 125II, CA 72-4, CA 15-3 and macrophage colony stimulating factor (M-CSF). The four tumor marker values were then used as inputs to an ANN derived using a training set from 100 apparently healthy women, 45 women with benign conditions arising from the ovary and 55 invasive epithelial ovarian cancer patients (including 27 stage I/II cases). A separate validation set from 27 apparently healthy women, 56 women with benign conditions and 35 women with various types of malignant pelvic masses was used to monitor the ANN's performance during training. An independent test data set from 98 apparently healthy women and 52 early stage epithelial ovarian cancer patients (38 stage I and 4 stage II invasive cases and 10 stage I borderline ovarian tumor cases) was used to evaluate the ANN. Results. ROC analysis confirmed the overall superiority of the ANN-derived composite index over CA 125II alone ( p = 0.0333). At a fixed specificity of 98%, the sensitivities for ANN and CA 125II alone were 71% (37/52) and 46% (24/52) ( p = 0.047), respectively, for detecting early stage epithelial ovarian cancer, and 71% (30/42) and 43% (18/42) ( p = 0.040), respectively, for detecting invasive early stage epithelial ovarian cancer. Conclusions. The combined use of multiple tumor markers through an ANN improves the overall accuracy to discern healthy women from patients with early stage ovarian cancer. Analysis of multiple markers with an ANN may be a better choice than the use of CA 125II alone in a two-step approach for population screening in which a secondary test such as ultrasound is used to keep the overall specificity at an acceptable level.

Elevated carbohydrate antigen 125 levels in hypertrophic cardiomyopathy patients with heart failure

Carbohydrate antigen 125 (CA 125), known as a tumor marker for ovarian cancer, has been reported to increase and relate to severity in heart failure patients with systolic dysfunction. Hypertrophic cardiomyopathy (HCM) has a wide clinical spectrum that often includes heart failure symptoms. The aim of this study was to evaluate the role of CA 125 in HCM patients, its relation to severity of symptoms, and degree of diastolic dysfunction. CA 125 blood levels were determined in 32 HCM patients (21 male; age 51.3 +/- 18.4 years) and in 30 healthy volunteers (19 male; age 49.6 +/- 16.1 years). Echocardiographic examinations were performed in all patients. The results were grouped according to clinical status (New York Heart Association class) of the patients. The mean serum level of CA 125 was 14.6 +/- 23.8 U/ml in the study group and 7.6 +/- 4.8 U/ml in the control group. There was no significant difference between the groups (P = 0.12). CA 125 levels increased as the New York Heart Association functional class increased (class I/II: 6.2 +/- 2.4 U/ml; class III: 30.6 +/- 36.4 U/ml; P < 0.001). The mean CA 125 level in functional class III patients (30.6 +/- 36.4 U/ml) was significantly higher than that of the control group (7.6 +/- 4.8 U/ml) (P < 0.001) and the functional class I/II group (6.2 +/- 2.4 U/ml) (P < 0.001). There was a significant difference over all three diastolic dysfunction groups with respect to CA 125 levels (4.9 +/- 1.3 U/ml in impaired relaxation group, 11.8 +/- 6.9 U/ml in pseudonormal group, and 52.6 +/- 45.6 U/ml in restrictive filling group; P < 0.0001). Serum CA 125 is related to the clinical severity of HCM. Whether CA 125 has a specific biological role in HCM requires further investigation.

Neurologic Improvement after High-dose Intravenous Immunoglobulin Therapy in Patients with Paraneoplastic Cerebellar Degeneration Associated with Anti-Purkinje Cell Antibody

Paraneoplastic cerebellar degeneration (PCD) is a rare syndrome associated with systemic malignancies, most in lung and ovarian cancer. Cerebellar ataxia has previously been associated with the presence of anti-Purkinje cell antibodies (anti-Yo) in the serum and cerebrospinal fluid and responses to therapy are uncommon. We reported two patients were identified with delayed onset of PCD associated with high titer of CSF anti-Yo (1:30,000, 1:320 U/ml) and a marked elevation of tumor markers for ovarian cancer (CA-125 17,700 ng/ml, 43 ng/ml) titer 1 year and 6 months prior to discovery of the carcinoma. Both developed subacute onset of severe ataxia, dysarthria, tremor, nystagmus with progression to severe debilitation (wheelchair bound or bedridden status). One of these patients also developed dysphagia that required PEG tube feeding. They were treated with six cycles of intravenous immunoglobulin (IVIG) 0.4 gm/kg/day x 5 days, every 4-6 weeks in conjunction with combination chemotherapy of Taxol and Carboplatin after the surgical resection of ovarian cancer. In each case, a significant improvement of neurological deficits were seen after the third cycle of IVIG, approximately 4 months after initiation of treatment. This type of delayed response is contrary to the previous reports. Both patients could ambulate without assistance in correlation with dramatic decrease in anti-Yo titer (1:80, 1:320 U/ml) and CA-125 (11 ng/ml, 8 ng/ml). This is a first report of benefit from IVIG in patients with late onset of PCD, which showed a delayed response with significant neurological improvement.