what can cause your ca 125 markers to be elevated
Open Respir Med J. 2009; 3: 123–127.
Ca-125: A Useful Mark to Distinguish Pulmonary Tuberculosis from Other Pulmonary Infections
J Fortún
aneInfectious Diseases Department Ramón y Cajal Infirmary, Madrid, Spain
P Martín-Dávila
1Infectious Diseases Department Ramón y Cajal Hospital, Madrid, Kingdom of spain
R Méndez
1Infectious Diseases Section Ramón y Cajal Hospital, Madrid, Kingdom of spain
A Martínez
1Infectious Diseases Department Ramón y Cajal Hospital, Madrid, Spain
F Norman
aneInfectious Diseases Department Ramón y Cajal Hospital, Madrid, Kingdom of spain
J Rubi
2Biochemistry Department, Ramón y Cajal Hospital, Madrid, Kingdom of spain
Due east Pallares
2Biochemistry Section, Ramón y Cajal Hospital, Madrid, Spain
E Gómez-Mampaso
iiiMicrobiology Department, Ramón y Cajal Hospital, Madrid, Spain
S Moreno
1Infectious Diseases Department Ramón y Cajal Hospital, Madrid, Spain
Received 2009 February 18; Revised 2009 May 26; Accepted 2009 Sep 28.
Abstract
Introduction:
Ca-125 is secreted past unlike celomic epitheliums. Serum levels may be increased in cancerous diseases, like ovarian cancer merely also in other medical atmospheric condition, such as pulmonary and extrapulmonary tuberculosis.
Methods:
From Jan-04 to Dec-06 a retrospective report analyzing Ca-125 levels in serum samples from patients with a diagnosis of pulmonary TB, was performed. These results were compared with those samples obtained from patients with non-TB pulmonary infections.
Results:
Eighty-nine patients were included in the report, 30-five with pulmonary TB and 54 with other respiratory infections. In patients with TB, the hateful Ca-125 value was 104.9 IU/ml (SD: ± 136.ane). In the control grouping, mean value was 27.i IU/ml (SD: ±19.7). The optimal cutting-off for pulmonary tuberculosis was 32.5 IU/ml (sensitivity: 68.half dozen%, specificity: 77.8%). Pulmonary TB was the only factor associated with a Ca-125 level >32.v. In ten patients with TB, Ca-125 levels were available ≥ 2 months after starting TB therapy and a decrease during treatment was shown.
Conclusions:
Ca-125 values increase in patients with pulmonary TB and decline to normal values during treatment. Decision of Ca 125 may exist usedin patients with a negative sputum AFB stain.
Keywords: Ca-125, tuberculosis, pneumonia.
INTRODUCTION
Patients with tuberculosis (TB) present pulmonary interest most frequently. Microscopic examination of acid-fast stained sputum smears remains the nearly useful diagnostic method and positive samples institute indications for initiation of TB therapy and respiratory isolation. However, in some cases of pulmonary TB acid-fast bacilli stains in sputum samples may be negative or respiratory specimens may not be available, and other methods have to be used to establish the diagnosis of TB. Autonomously from microbiological molecular diagnostic tests, unlike biochemical parameters have been proposed as helpful tools for this purpose, including various markers of cellular activity, astute phase reactants and enzymes [1-v].
The tumor mark Ca-125 has been proposed every bit a useful diagnostic tool for tuberculosis. Ca-125 serum concentrations are known to rise in some benign and cancerous diseases [6, 7]. High levels of Ca-125 have been reported in patients with pulmonary and extra-pulmonary tuberculosis, including pleural, peritoneal, pelvic, milliary, and intra-abdominal disease. The diagnostic value of Ca-125 to help differentiate pulmonary tuberculosis from other pulmonary infections has been poorly studied [8-fourteen].
In order to asses the efficacy of Ca-125 serum levels in differentiating pulmonary tuberculosis from bacterial pneumonia and other respiratory infections in patients with fever and pulmonary infiltrates, a retrospective study was performed.
METHODS
The written report was performed at the Ramón y Cajal Hospital, a 1000-bed tertiary referral Hospital (Madrid, Espana), during a three year period (January 2004 to December 2006). By protocol, tumoral markers determinations are included in the ordinary biochemical grade awarding. They are obtained from all patients admitted in the unit for differential diagnosis purpose, including malignancy, in patients with lung infiltrates.
Ca-125 was determined by an electro-chemillumine-scence test (Elecsys 1010, Roche), including a radioimmuno analysis (RIA) Packard Gamma counter.
In all cases, tuberculosis was confirmed past positive culture in sputum or other tract respiratory samples. Serum Ca-125 levels were compared in patients with a diagnosis of TB infection versus patients with a diagnosis of bacterial pneumonia or other pulmonary infections. Patients with lung infiltrates related with oncologic procedure, heart failure, idiopathic interstitial pneumonitis or other non-infectious processes were excluded.
ROC curves were used to determine the optimal cut-off value of serum Ca-125 which could distinguish TB from other pulmonary infections with the highest sensitivity, specificity, and predictive values [15]. The curve obtained, allowed the adding of the slope and the expanse under the curve (AUC).
For some patients in the TB group, Ca-125 was also measured during follow-up (2 to four months after starting TB treatment).
For the analysis of risk factors associated with TB infection, a example-command study was performed, considering TB patients as cases and patients with non-TB pulmonary infection as controls.
Hospital records for all patients included in both groups to obtain information regarding clinical, radiological, and event characteristics were examined. The association between categorical variables was performed using Chi-squared tests with the Yates correction or Fisher Exact Test (two-tailed) as necessary. Continuous variable association was analysed with the Mantel-Haenszel test. Statistical assay was performed with the SPSS software package (version xi.0; SPSS Inc, Chicago, IL).
Informed consent: co-ordinate to the IRB, only patients' oral informed consent for the anonymous treatment of their data is required when the sudy protocol is the same used for regular medical attention of these patients in our hospital.
RESULTS
A full of 89 patients was included in the study. 30 5 patients had culture positive pulmonary tuberculosis and 54 patients had other causes of fever and pulmonary infiltrates.
Patient characteristics are shown in Table 1 .
Table 1.
Characteristics of Patients with Pulmonary Tuberculosis (Cases) and Patients with Other Causes of Pulmonary Infections (Controls)
| Cases (due north=35) | Controls (north=54) | |
|---|---|---|
| | ||
| Clinical presentation | ||
| -Pulmonary tuberculosis | 35 | 0 |
| -Lobar community caused pneumonia | 0 | 37 |
| -Acute exacerbation in COPD * | 0 | eight |
| -Nosocomial pneumonia | 0 | iv |
| -Interstitial community acquired pneumonia # | 0 | 4 |
| -Empyema | 0 | 1 |
| -Pleuropericarditis | 0 | 1 |
| | ||
| Systemic disease | ||
| -HIV | 9 | vii |
| -Vasculitis | 0 | 1 |
| -Collagen affliction | 0 | 1 |
| -Steroid therapy | 1 | 2 |
| -Diabetes | 1 | 3 |
| | ||
| Clinical picture | ||
| -Acute (< 2 weeks) | 9 | 26 |
| -Sub-acute | 32 | 22 |
| | ||
| Pulmonary infiltrate | ||
| -Alveolar | 20 | 32 |
| -Interstitial | 1 | eleven |
| -Pleural effusion | 4 | 8 |
| -No infiltrate | 1 | 12 |
| | ||
| Basal Ca-125 level (IU/ml) | ||
| -Hateful (± DE) | 104.9 (± 136.one) | 27.1 (± 19.vii) |
| -Median | 46 | 24 |
| -Range | 10-500 | 5-123 |
| | ||
| Ca-125 level during therapy (2-4 month (IU/ml) | ||
| -Mean (± DE) | 59.5 (± 88.5) | |
| -Median | 31 | |
| -Range | xiii-63 | |
In the control group most patients (68%, 37 patients) had a confirmed diagnosis of community-acquired pneumonia. 8 patients (15%) had chronic obstructive pulmonary disease (COPD) and were diagnosed of acute exacerbations with response to antibody therapy. The remaining ix patients were diagnosed of nosocomial-acquired pneumonia (n=four), interstitial pneumonia responding to clarithromycin therapy (n=iii), empyema (due north=one) and pleuropericarditis (due north=ane).
Sixteen patients (18%) had HIV infection; of these, nine patients had tuberculosis and seven patients had other pulmonary infections. HIV-infected patients had a median CD4 cell count lower than HIV-negative controls (124/ mm³, range: 12-358 vs 203 cells/mm3, range: 84-540), although this was non statistically significant.
Ca-125 serum levels were significantly higher in patients with tuberculosis (mean ± SD, 104.9 ± 136.one IU/mL, median: 46 IU/mL) than in the control group (mean±SD, 27.1 ± 19.vii IU/ml, median: 24). ROC bend analysis showed a relationship between the diagnosis of TB and Ca-125 values, with an AUC of 0.77 (95% asymptotic confidence interval: 0.66-0.87). The optimal cut-off value of Ca-125 for TB diagnosis was 32.5 IU/ml, with a sensitivity, specificity, positive predictive value and negative predictive value of 68.half-dozen%, 77.8%, 66.vii% and 79%, respectively.
A 68.half dozen% of patients with pulmonary tuberculosis showed Ca 125 serum levels >32.five IU/ml vs a 22% of patients with other pulmonary infections (p<0.01). No significant association was found between Ca 125 levels >32.five IU/mL and gender, clinical and radiological presentation, including pleural effusion, extra pulmonary manifestations and HIV infection.
Ca 125 levels were adamant in ten patients with pulmonary TB during follow-up, afterward two to iv months of therapy. The hateful Ca 125 value was 59.5 (± 88.5) IU/ml and the median was 31 (range: 13 to 63) (Table one ). Fig. ( one ) shows the subtract of Ca 125 values observed in these ten patients during TB therapy.
Basal and mail service-therapy (2-iv months) Ca-125 levels in 10 patients with pulmonary tuberculosis.
Word
Ca 125 antigen is a big molecular-weight glycoprotein synthesized by unlike cells originating from the celomic epithelium. Although classically it has been used to monitor the grade of ovarian epithelial cancer, at that place are other circumstances associated with high serum Ca 125 levels, which decrease the sensitivity and specificity of the exam when used generally/not-specifically. Ca 125 levels have been determined in mesothelial jail cell lines by immuno-histochemistry methods and in bronchial epithelial cells past immunoperoxidase stained techniques [16]. If these cells are activated by physiological or pathological reactions, such every bit menstruation, inflammation or cancer, Ca 125 is released.
Many malignant processes have been associated with high serum Ca 125 levels: including several tumors, other than ovarian epithelial cancer, such as pulmonary, hepatobiliary, gastric, colorectal, pancreatic neoplasias and non-Hodgkin lymphomas with mediastinal and/or abdominal location [17-20]. Other circumstances related with the stimulus of mesothelial cells, such every bit peritoneal dialysis, pelvic inflammatory disease, endometriosis, pancreatitis and autoimmune disorders accept besides been associated with elevated serum Ca 125 levels [7, 21-23]. Mirales et al. accept reported increased Ca 125 levels (>35 IU/ml) in patients with previous surgery, pulmonary disease, eye failure, cirrhosis and intrabdominal illness [24].
Other studies have confirmed high serum Ca 125 levels in tuberculosis, mainly in extrapulmonary locations with intestinal involvement [10,xi,25-30]. Some authors have reported elevated serum Ca 125 levels in benign pulmonary diseases, including tuberculosis [31].
Ronay et al. demonstrated the expression of Ca-125 in the proximity of tuberculous granulomas using an immuno-histochemical method in two patients with peritoneal TB probably due to proliferation of mesothelial cells [32]. Another study, using anti Ca 125-labeled specific antibodies confirmed positive capture of antibodies on giant epithelioid cells in patients with pleural and peritoneal TB [33].
A small number of studies have analyzed the part of serum Ca 125 in patients with pulmonary TB. A instance-control study comparing patients with agile tuberculosis with patients with cured tuberculosis confirmed a significant elevation of serum Ca 125 levels in patients with TB and a normalization of these levels during therapy [34]. Mean Ca 125 levels in patients with tuberculosis were significantly college than that observed in patients with past tuberculosis, or healthy patients. Moreover, a significant reduction of Ca 125 levels was observed in patients with pulmonary tuberculosis during therapy. For a Ca 125 value of 31 IU/ml, authors confirmed a sensitivity and specificity of 97.5% and 100%, respectively [34]. This normalization of Ca 125 values during therapy of patients with pulmonary tuberculosis has besides been observed in other studies [12,13,35,36].
An important contribution of the nowadays study is the potential role of Ca 125 measurements in patients with fever and pulmonary infiltrates of unknown aetiology, with elevated levels supporting a diagnosis of pulmonary tuberculosis in patients where the disease was suspected but respiratory samples had negative AFB stains. In the present written report AFB stains were positive in sputum in all simply 1 case; in this case basal Ca-125 level was 150 IU/ml.
Aoki et al., demonstrated a sensitivity, specificity and accuracy of 100%, 75% and 84%, respectively, for serum Ca 125 >35 IU/ml in patients with pleural tuberculosis [three]. Patients with other pleural pathologies, such as mesothelial neoplasias, empyemas, para-pneumonic pleural effusions or autoimmune disorders, were used equally controls. Results obtained with serum Ca 125 levels were similar or ameliorate than those obtained using pleural ADA (adenosine deaminase) levels >45 IU/ml, with a sensitivity, specificity and accurateness for this test of 81.8%, 89.three% and 87.two%, respectively [iii]. In the present study the number of patients with pleural effusion was low (four in the TB grouping and 8 in the command group), but all patients with tuberculosis and pleural effusion had Ca 125 serum levels >35 IU/ml (data not shown).
The present written report has several limitations. This is a retrospective study and a specific protocol focusing on the human relationship between Ca-125 levels and tuberculosis was not applied. Control patients were non homogeneous and included a miscellaneous of patients with a diagnosis of bacterial pneumonia or other pulmonary infections. A low number of patients with pleural effusion were included and a specific assay focused in these patients was not possible. Patients with lung infiltrates related with oncologic procedure, but unsuspected at admission, were excluded. Finally, in only ten patients a 2nd determination of Ca 125 serum level was bachelor for outcome analysis.
In determination, the present study seems to confirm by mimicking the results of other similar studies, that serum Ca 125 levels in patients with pulmonary tuberculosis are significantly higher than that observed in patients with other causes of pulmonary infection. Ca 125 measurement may be recommended if pulmonary tuberculosis is suspected and AFB stain of respiratory samples is negative or non available. The decrease in levels during therapy may be useful to monitor patients with pulmonary tuberculosis.
ACKNOWLEDGEMENTS
We accept had full access to all of the data in the study and have responsibility for the integrity of the information and the accurateness of the data analysis.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788741/
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