Background An increase of some tumor associated antigens (TAAs) has been reported in Systemic Sclerosis (SSc) and interstitial lung diseases (ILD), and SSc patients had higher risk of cancer compared to general population.
Objectives The aim of our study was to evaluate the serum levels of TAAs in patients with SSc and ILD and to correlate these levels to the severity and the progression of lung disease and their role during follow-up.
Methods Data from 80 consecutive SSc-patients with evidence of ILD on high resolution computed tomography (HRCT) and/or restrictive lung disease on pulmonary function test (PFTs), were retrospectively collected. TAAs including CEA, CA19.9, Ca15.3, CA125, Cyfra21.1 and enolase were determined. PFTs values and HRCT scores performed after 2 years were available from database.A period of 4 years follow-up for each patient was available in order to investigate the occurrence of any malignancy.
Results 43.7% patients presented an increase of at least one TAA. Among the different TAAs, 28.7% had an increase of CA15-3, 17.5% of CA19.9, 15% of Cyfra21.1, 12.5% of TPA, while CEA, enolase and CA125 were above the cut-off value in 8 patients. The increase of at least one TAA was associated with the diffuse skin involvement and with anti-Scl70 positivity. SSc patients with an increase of any TAA presented lower FVC values, higher interstitial score and higher alveolar score at baseline compared with SSc patients without TAAs increase (p<0.01 for all comparisons).The levels of CA15-3 and CEA inversely correlated with FVC (R=-0.2,p≤0.04 for both correlations) and directly correlated with the alveolar score (R=0.43, p<0.0001; R=0.24, p=0.04; respectively) and interstitial score at baseline (R=0.47, p<0.0001; R=0.31, p=0.007, respectively). After two years, 20 patients (25%) presented a decrease of FVC>10% and 18 patients (22.5%) a worsening of HRCT scores. Patients with worsening of interstitial score presented at baseline higher levels of CA15-3 and of CA125 with respect to patients with a stable interstitial score (p=0.01 and p=0.002, respectively). During the follow-up, 7 patients developed a cancer and all of them had already an increase of at least one TAA at baseline (despite the negative baseline screening for neoplasia), while none of the patients without increasing of TAAs at baseline developed malignancies during the follow-up (p=0.003). Considering the 60 patients in which at least another determination of TAAs was available during follow-up, values of specific TAA (CA15.3, CA19.9 and CEA) increased over time in patients who developed cancer, while TAAs levels tended to remain stable in others. At multivariate analysis, CEA upper the cut-off value emerged as an independent predictor of development of malignancies [RR 25.2 (CI: 29.0-220.0), p=0.004].
Conclusions TAAs can be elevated in the sera of SSc patients. CA15.3 and CEA correlate with the functional and radiological lung damage suggesting a possible role as “severitiy biomarkers”, while their prognostic significance in ILD is not clear. A close follow-up is necessary in SSc patients because of the increased risk of cancer, overall in patients with increased TAAs.
Disclosure of Interest None declared