Original ArticleImmunohistochemical expression of tumor antigens MAGE-A3/4 and NY-ESO-1 in renal oncocytoma and chromophobe renal cell carcinoma
Introduction
Renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC) are both renal epithelial neoplasms thought to arise from intercalated cells of collecting ducts. Together they account for approximately 10% of surgically removed renal epithelial tumors [4]. Oncocytomas are benign, non-encapsulated neoplasms composed of round-to-polygonal cells with densely granular eosinophilic cytoplasm (so-called oncocytes), which form compact nests, acini, tubules, or microcysts. Oncocytomas occasionally have sclerosed central area [4], [14]. ChRCC are solid tumors made up of large polygonal cells with prominent cell membranes, pale cytoplasm, and usually a perinuclear halo. They include three subtypes: classic, eosinophilic, and mixed [24]. The majority of ChRCCs are stage T1 and T2, and only a few cases of lymph node and distant metastasis have been described [4].
The distinction between RO and ChRCC, especially its eosinophilic variant, can sometimes be difficult due to their overlapping morphological characteristics. Histology, ultrastructural examination, and staining with Hale's colloidal iron can be used for their differentiation in daily practice. In recent years, there have been attempts to find an immunohistochemical marker that could also help in diagnostics [1], [5], [15], [16], [17], [19].
Cancer testis antigens (CTAs) comprise a family of more than 40 genes expressed in a wide variety of malignant tumors [21]. In normal tissue, their expression is mostly limited to germ cell lines. Because of their ability to induce immune responses, CTAs are being evaluated as targets for therapeutic cancer vaccines [3], [23].
There is only limited information available on the expression of CTAs in different histological subtypes of renal tumors [18], [25].
The aim of this study was to investigate the immunohistochemical expression of MAGE-A3/4 and NY-ESO-1 CTAs in ROs and ChRCCs. To our knowledge, there are no studies regarding the immunohistochemical expression of these CTAs in RO and/or ChRCC.
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Tissue samples
Pathology reports of histologically confirmed ROs and ChRCCs diagnosed at two Departments of Pathology (Ljudevit Jurak University Department of Pathology, Sestre Milosrdnice University Hospital, and Department of Pathology, University Hospital Dubrava, Zagreb) were reviewed. The diagnosis of all cases was established according to the criteria set forth in the 2004 WHO Classification of Tumors of the Urinary System and Male Genital Organs [4]. There were 35 cases in total: 17 ROs and 18 ChRCCs.
Results
Clinical and histological data and results of immunohistochemical staining are summarized in Table 1, Table 2. Fifteen ROs (88.2%) were positive for both MAGE-A3/4 and NY-ESO-1 antigens (Fig. 1A and B). Regarding ChRCC, 7 (38.9%) showed a positive reaction for MAGE-A3/4 antigen and 6 (33.3%) for NY-ESO-1 antigen (Fig. 1C and D). Median MAGE-A3/4 expression was moderately positive in ROs and negative in ChRCCs. The difference in MAGE-A3/4 expression between two tumor groups was statistically
Discussion
Renal oncocytoma and ChRCC, especially its eosinophilic variant, can often be confused with one another due to their similar morphology. The distinction between these tumors is clinically relevant because they have different biological courses; RO is a benign neoplasm, whereas ChRCC has malignant potential, particularly its sarcomatoid variant which is associated with more aggressive tumor behavior [4].
There have been numerous studies that explored the possible use of various
Acknowledgments
This work was supported in part by the Ministry of Science, Education and Sports, Croatia, project numbers 108-1081870-1884 and 134-0000000-3381.
We would like to thank Dr. Stela Bulimbašić from the Department of Pathology, University Hospital Dubrava, Zagreb, Croatia, for providing us with paraffin blocks of tumor tissue.
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