Diagnosis and origin determination of malignant pleural effusions through the use of the breast cancer marker human mammaglobin

Our plain-English summary of Diagnosis and origin determination of malignant pleural effusions through the use of the breast cancer marker human mammaglobin, by S. Roncella, P. Ferro, M.C. Franceschini, et al (Diagnostic Molecular Pathology, 2010).

The study

• Authors: S. Roncella, P. Ferro, M.C. Franceschini, B. Bacigalupo, P. Dessanti, M. Sivori, A.M. Carletti, V. Fontana, P.A. Canessa, M.P. Pistillo, F. Fedeli
• Journal: Diagnostic Molecular Pathology
• Published: 2010;19(2):92-8
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

As was reported that human mammaglobin (hMAM) may be expressed in malignant pleural effusions (PEs), we investigated the relevance of hMAM reverse-transcriptase polymerase chain reaction (RT-PCR) for their diagnosis and determination of primary origin. Two hundred and twenty-eight malignant (132 male, 96 female) and 185 benign (132 male, 53 female) PEs were investigated. Statistical analyses evaluated the diagnostic performance parameters in all PEs and in cytologically negative malignant PEs, the association between hMAM and benign or malignant status by the direct index of correlation [diagnostic odds ratio (DOR)], chi test, and P value (P). In addition, the discriminative diagnostic power of hMAM expression, independently in breast cancer, lung cancer (LC), malignant mesothelioma (MM), and other cancers was evaluated. In the entire patient population, hMAM was detected in 45.6% and 5.4% of malignant and benign PEs, respectively, in the male group in 41.7% and 4.5% and in the female group in 51.0% and 7.5% of malignant and benign PEs, respectively. A statistically significant correlation between hMAM and malignancy was found in the entire population (DOR=14.68, P<0.001) and in the male (DOR=15.00, P<0.001) or female (DOR=12.77, P<0.001) groups. hMAM RT-PCR increased the diagnostic rate of malignant PEs as it allowed us to detect as malignant 32.1% of cytologically negative PEs. In female patients the positivity of hMAM indicated with higher probability (50.8%) the origin of PEs from breast cancer but lower probability from LC (17%), MM (9.4%), or other cancers (15.1%), whereas in male patients it indicated with similar probability (about 40%) the origin from LC or MM. Our results suggest that hMAM RT-PCR may provide information both in the diagnosis of PE and in the search for the primary site of neoplasia, either in male or female patients.

In plain English

This diagnostic study from Italy tested whether finding human mammaglobin (hMAM) in pleural effusions (fluid around the lungs), using a laboratory test called RT-PCR, could help separate effusions caused by cancer from benign ones and suggest where the cancer started. Effusions came from 413 patients diagnosed between 2002 and 2007 at a hospital in Sarzana: 228 malignant and 185 benign. hMAM was found in 104 of 228 malignant effusions (45.6%) and in 10 of 185 benign effusions (5.4%). The diagnostic odds ratio was 14.68 (95% confidence limits 7.37 to 29.22). hMAM was found in 29 of 80 effusions from malignant mesothelioma (36.2%). Among 106 malignant effusions in which cytology found no cancer cells, 34 were hMAM-positive. In men, a positive test pointed about equally to lung cancer (41.0%) or mesothelioma (39.3%). The authors concluded that a positive test is highly suggestive of malignancy, but stated that a negative test does not exclude cancer. Asbestos exposure was not studied. The authors mentioned it only to explain why mesothelioma is common in the area.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic test evaluation: hMAM detected by nested RT-PCR in pleural effusion samples, compared between malignant and benign effusions and against cytology
• Who was studied: 413 Italian patients diagnosed between February 2002 and October 2007 at San Bartolomeo Hospital, Sarzana. There were 228 malignant pleural effusions (132 males, 96 females), including 80 from malignant mesothelioma (67 males, 13 females), and 185 benign effusions (132 males, 53 females). 106 of the malignant effusions were cytology-negative.
• Exposure: No asbestos exposure was measured. The study evaluated a laboratory test (nested RT-PCR for hMAM mRNA in pleural fluid). In the discussion, the authors noted that chronic exposure to industrial hazards such as asbestos is particularly high in La Spezia, and that malignant mesothelioma is the second most common malignancy in males there.
• Main results:
  • Across all patients, hMAM was detected in 104 of 228 malignant effusions (45.6%) and in 10 of 185 benign effusions (5.4%).
  • Diagnostic odds ratio for hMAM and malignant status was 14.68 (95% CL 7.37 to 29.22) in the entire population (p less than 0.001).
  • Diagnostic odds ratio was 15.00 (95% CL 6.17 to 36.49) in males and 12.77 (95% CL 4.27 to 38.17) in females.
  • By cancer type, hMAM was positive in 27 of 32 breast cancer effusions (84.4%), 34 of 77 lung cancer (44.1%), 29 of 80 malignant mesothelioma (36.2%) and 14 of 39 other cancers (35.9%).
  • Among the 106 cytology-negative malignant effusions, 34 were hMAM-positive (sensitivity 32.1%).
  • In males with a positive test, the estimated probability of lung cancer was 41.0%, of malignant mesothelioma 39.3%, and of other cancers 9.8%.
  • In females with a positive test, the estimated probability was 50.8% for breast cancer, 17.0% for lung cancer, 9.4% for malignant mesothelioma and 15.1% for other cancers.
• The authors' conclusion: The authors concluded that, although further studies in other clinical settings are needed, the hMAM RT-PCR test could help in diagnosis because a positive result is highly suggestive of malignancy for a pleural effusion.
• Limitations the authors state:
  • A negative test does not exclude a malignant origin. Among hMAM-negative patients, the probability of malignancy was 39.1% in males and 49.0% in females.
  • The predicted probabilities depend on how often each disease is diagnosed locally, so they may differ in other areas. The local frequency of mesothelioma was high.
  • Further studies are needed to assess the test in other clinical settings.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Odds Ratio, Lung Cancer, Malignant Mesothelioma.

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