Genetic testing may be the key to distinguishing an unusually aggressive and sneaky type of mesothelioma from an unrelated condition.
Chinese researchers have found that a protein emitted by the GATA3 gene is frequently detected in sarcomatoid malignant mesothelioma, an atypical form of mesothelioma that is unusually aggressive and resistant to treatment.
Sarcomatoid mesothelioma, sometimes referred to as spindle cell mesothelioma due to the odd shape of affected cells, can be difficult to diagnose due to its similarity to two unrelated conditions: the equally deadly lung sarcomatoid carcinoma and the more nebulous organizing pleuritis.
Compounding this issue is that most sarcomatoid mesothelioma cells do not emit many of the usual mesothelioma markers, the researchers reported in the Feb. 11 edition of Virchows Archiv, a European pathology journal.
GATA Test ’Em All!
Knowing that the GATA3 protein can serve as a marker for two other forms of cancer — breast cancer and urothelial carcinoma — and that GATA is “routinely” found in mesothelioma cases, the researchers decided to see whether GATA3 analysis could readily distinguish between sarcomatoid mesothelioma cells, lung sarcomatoid carcinoma cells and organizing pleuritis cells.
The team analyzed cell lines from 17 sarcomatoid mesothelioma patients, 12 lung sarcomatoid carcinoma victims and seven organizing pleuritis patients, comparing three forms of gene expression in each. In addition to testing GATA3 expression in the cells, they also compared levels of calretinin — a calcium-binding protein often used as a marker for other forms of mesothelioma — and the Wilms tumor gene, which is commonly found in leukemia and solid tumors.
When comparing sarcomatoid mesothelioma results to lung sarcomatoid carcinoma cases, they found GATA3 in 70.6 percent of sarcomatoid mesothelioma cases, versus only 16.7 percent for lung sarcomatoid carcinoma. Calretinin levels were slightly less predictive, showing up in 52.9 percent of sarcomatoid mesothelioma cases, as compared to 8.3 percent of lung sarcomatoid carcinoma results.
Wilms tumor testing actually netted the best results of the bunch, with it emerging in 64.7 percent of sarcomatoid mesothelioma results and none of the lung sarcomatoid carcinoma cases.
The team did not disclose numbers for its comparison of sarcomatoid mesothelioma cells with organizing pleuritis cells, noting that all organizing pleuritis tests showed “partial or diffuse expression” for the Wilms tumor gene and two other tests but no results for GATA3 or calretinin.
The report stated that combining the results of two or more of these tests yielded the best results, with a 100 percent specificity finding for sarcomatoid mesothelioma. The sensitivity of the tests, however, left something to be desired.
Analyzing for calretinin and Wilms tumor gene expression avoided false-positives only 23.5 percent of the time, though the addition of GATA3 testing hiked this number to 64.7 percent.
Based on these findings, the team concluded that GATA3 has “excellent sensitivity and specificity” as a marker for sarcomatoid mesothelioma, and combining all three tests was the best means of distinguishing sarcomatoid mesothelioma cells from lung sarcomatoid carcinoma cells.