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Prognostic significance of different immunohistochemical S100A2 protein expression patterns in patients with operable nonsmall cell lung carcinoma

Authors Hountis P, Foukas, Matthaios D, Kefala M, Chelis L, Pantelidaki E, Panayiotides, Karakitsos P, Kakolyris

Received 29 July 2012

Accepted for publication 12 September 2012

Published 21 November 2012 Volume 2012:5 Pages 363—373

DOI https://doi.org/10.2147/OTT.S36474

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3



Panagiotis Hountis,1 Periklis G Foukas,2 Dimitrios Matthaios,3 Maria Kefala,2 Leonidas Chelis,3 Aikaterini Pantelidaki,4 Ioannis G Panayiotides,2 Petros Karakitsos,5 Stylianos Kakolyris3

1Department of Thoracic Surgery, Athens Naval Hospital, Athens, 2Second Department of Pathology, University of Athens Medical School, “Attikon” University Hospital, Athens, 3Department of Oncology, Democritus University of Thrace, Alexandroupolis, 4Department of Pathology, Evangelismos General Hospital, Athens, 5Department of Cytopathology, University of Athens, Medical School, “Attikon” University Hospital, Athens, Greece

Abstract: S100 proteins are involved in carcinogenesis, metastasis, and survival. S100A2 is a member of the S100 family, and its expression and precise role in patients with non-small cell lung carcinoma (NSCLC) has been debated. Therefore, we examined the immunohistochemical expression patterns of S100A2 in NSCLC in relation to clinicopathological parameters, important molecular biomarkers, and patient outcome. Microarray data for 74 paraffin-embedded specimens from patients with NSCLC were immunostained for S100A2 and p53 proteins. Immunohistochemical staining patterns of S100A2 in the NSCLC tissue samples examined were either nuclear (nS100A2), cytoplasmic (cS100A2), or both. A significant association between nS100A2 positivity and better disease-free interval was observed (hazards ratio 0.47; 95% confidence interval 0.23–0.99; P = 0.047). Similarly, cS100A2 negativity was marginally associated with shorter overall survival (P = 0.07). Patients without lymphatic infiltration and an earlier disease stage had significantly better overall survival and disease-free interval. The S100A2 expression pattern in operable NSCLC varies widely, and this differential expression (nuclear, cytoplasmic or both) seems to correlate with prognosis. Intensity of expression was highest in the early and advanced stages, and equally distributed in the middle stages. This observation may be indicative of a dual role for this protein both during earlier and advanced disease stages, and may also explain the differential immunoexpression of S100A2. Analysis of the disease-free interval showed that nS100A2-negative and p53-positive expression was associated with a statistically significant (P = 0.003) shorter disease-free interval in comparison with nS100A2-positive and p53-negative expression (12 versus 30 months, respectively). Further studies are required to establish whether S100A2 protein may have a substantial role as a prognostic or predictive indicator in this unfavorable group of patients.

Keywords: S100A2, expression, lung cancer, thoracic surgery

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