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Analysis of Cancer/Testis Antigens in Sporadic Medullary Thyroid Carcinoma: Expression and Humoral Response to NY-ESO-1

Cancer Bioimmunotherapy Unit (M.M., S.C., L.S., E.C., F.C., M.A.), Department of Medical Oncology, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, 33081 Aviano, Italy; Dipartimento di Biologia e Patologia Cellulare e Molecolare (G.R., M.V.), Università Federico II, 80131 Naples, Italy; Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy (G.F.); and Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore" (G.R.), Consiglio Nazionale delle Ricerche, Istituto di Endocrinologia (R.E., C.R., A.P.), 56124 Pisa, Italy

Address all correspondence and requests for reprints to: Mario Vitale, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Via S. Pansini 5, 80131 Napoli, Italy. E-mail: mavitale{at}unina.it.

Cancer/testis antigens (CTA) are tumor-associated antigens expressed during ontogenesis, in a number of solid tumors but not in normal tissues except testis. Most of these CTA are highly immunogenic, eliciting a humoral and cellular response in the patients with advanced cancer, and are useful for tumor-specific immunotherapy. Medullary thyroid carcinoma (MTC) is a neoplasm derived from the parafollicular cells of the thyroid and occurs in either a sporadic or a familial form. In the present study, we examined by RT-PCR the expression of a number of genes encoding CTA in 23 surgical samples of sporadic MTC. Among the 11 cDNA antigens examined, RAGE, MAGE-4, and GAGE 1–2, were not expressed in any of the tissues. SSX 2 was present only in one tissue, whereas BAGE, GAGE 1–6, MAGE-1, MAGE-2, MAGE-3, and SSX 1–5 were detected in two to five samples. NY-ESO-1 cDNA was the most frequent, being detected in 15 of 23 examined samples (65.2%). Six (26.1%) tissues did not express any CTA-specific mRNA, whereas 10 tumors expressed only one gene (43.5%), 3 (21.4%) expressed 2 genes, and 4 displayed a broad CTA gene expression. NY-ESO-1 expression in primary MTC tissues significantly correlated with tumor recurrence. The presence of specific anti-NY-ESO-1 antibodies was searched in the sera of MTC-affected patients examined by ELISA using recombinant NY-ESO-1 protein. A humoral response against this CTA was detected in 6 of 11 NY-ESO-1 expressing patients (54.5%), and in 1 of 6 patients with NY-ESO-1-negative tumor. No anti-NY-ESO-1 antibodies were detected in healthy subjects (n = 17). The presence of anti-NY-ESO-1 antibodies was searched also in the sera of MTC affected patients whose tissues were not available for CTA analysis. Anti-NY-ESO-1 antibodies were present in 15 of 42 sera (35.7%), demonstrating that MTC is a neoplasm frequently associated with humoral immune response to NY-ESO-1. Serological survey may be useful as a way to identify patients with humoral immune response to NY-ESO-1 that provide a new attractive target for vaccine-based immunotherapy of MTC.

This work has been partly supported by Ministero dell’Università e della Ricerca Scientifica, Programa di Rilevante Interesse Nazionale (to G.R.), by Associazione Italiana per la Ricerca sul Cancro (to M.M.), by Consiglio Nazionale delle Ricerche, Comitato Scienze Biologiche e Mediche (to M.V.), and by Ministero della Salute, Progetto Ricerca Finalizzata (to M.M.).

Abbreviations: CT, Calcitonin; CTA, cancer/testis antigens; MTC, medullary thyroid carcinoma; NHS, normal human sera; TAA, tumor-associated antigens.

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