Abstract
BackgroundAnti-SOX2 antibody responses are observed in about 10 to 20% of small cell lung cancer (SCLC) patients. The aim of this study was to determine whether such responses reflect a particular pattern of SOX2 protein expression in the tumor and whether this pattern associates with clinical outcome.MethodsParaffin embedded tumor tissues, obtained from SCLC patients who had no evidence of paraneoplastic autoimmune degeneration, were evaluated for SOX2 expression by immunohistochemistry for both intensity and extent of staining. Sera from the same patients were tested for autologous antibodies against recombinant SOX2 by enzyme-linked immunosorbent assay (ELISA). Correlates between overall survival and various clinical parameters including SOX2 staining and serology were determined.ResultsSOX2 protein expression was observed in tumor tissue in 89% of patients. Seventeen patients (29%) were seropositive for SOX2 antibodies and, in contrast to SOX2 staining, the presence of antibody correlated with limited disease stage (p = 0.05). SOX2 seropositivity showed a significant association with the intensity of SOX2 staining in the tumor (p = 0.02) but not with the frequency of SOX2 expressing cells.ConclusionAnti-SOX2 antibodies associate with better prognosis (limited stage disease) while SOX2 protein expression does not; similar to reports from some earlier studies. Our data provides an explanation for this seemingly contrasting data for the first time as SOX2 antibodies can be observed in patients whose tumors contain relatively few but strongly staining cells, thus supporting the possible presence of active immune-surveillance and immune-editing targeting SOX2 protein in this tumor type.
Highlights
Anti-SOX2 antibody responses are observed in about 10 to 20% of small cell lung cancer (SCLC) patients
In line with these facts, SOX2 protein expression was shown to be an independent marker for worse outcome in early stage lung adenocarcinoma [4] and to associate with tumor aggression and higher grade in lung cancer [5]
SOX2 expression with lower grade and with better outcome in squamous cell carcinoma of the lung [6], and a recent study found a relation between SOX2 expression and advanced disease, as well as worse overall survival in SCLC [7]
Summary
Anti-SOX2 antibody responses are observed in about 10 to 20% of small cell lung cancer (SCLC) patients. SRY-homology box group B1 genes (SOX1, SOX2, SOX3) are known to function in neural plate, gut and lung development [1,2]; and SOX2 has a role in maintaining the pluripotent stem cell phenotype [3] In line with these facts, SOX2 protein expression was shown to be an independent marker for worse outcome in early stage lung adenocarcinoma [4] and to associate with tumor aggression and higher grade in lung cancer [5]. SOX2 expression with lower grade and with better outcome in squamous cell carcinoma of the lung [6], and a recent study found a relation between SOX2 expression and advanced disease, as well as worse overall survival in SCLC [7] These seemingly conflicting results could be due to tumor type specific behavior of SOX2, or technical reasons but they could be due to presence of unacknowledged confounding prognostic factors. Since anti-SOX2 antibodies are most frequently found in patients with small cell carcinoma of the lung (SCLC), we asked if immunity against SOX2 was related to its protein expression, and if either related to clinical parameters determining outcome in SCLC
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