BERKELEY, CA (UroToday.com) - CXp 11.2 translocation renal cell carcinoma (RCC) is a rare RCC subtype and is defined by at least 6 different translocations involving the Xp 11.2 chromosome, resulting in gene fusion between the transcription factor that binds to IGHM enhancer 3 (TFE3) and papillary RCC (PRCC) or alveolar soft part sarcoma locus (ASPL; also known as ASPSCR1). All fusion gene products are transcription-regulators, and these chimeric fusion proteins are thought to activate various target genes, thereby playing a central role in tumorigenesis. This RCC subtype normally affects children and young adults, and previous studies have reported approximately 80 cases.
Although the prognosis is usually good for younger patients with this tumor, the clinical course is more aggressive in older patients due to frequent lymph node metastasis. An accurate diagnosis is essential for prognostic prediction and development of a therapeutic strategy, since the potential efficacy of immune therapy for this carcinoma, as well as the utilization of tyrosine kinase inhibitors like sorafenib and sunitinib, has been demonstrated even in patients with advanced stage carcinoma.
Clinical diagnosis of this RCC subtype is difficult due to the absence of characteristic clinical features or family history. It is also difficult to diagnose this tumor histologically due to the presence of histological similarities with PRCC or clear cell RCCs. The absence of detailed examinations has led to misdiagnosis of a large number of tumors. Although Xp 11.2 translocation RCC may be suspected based on the histological evidence of a distinctive papillary architecture or presence of intratumoral psammomatous calcifications, immunohistochemical testing is necessary. Immunohistochemistry is a useful technique that can be performed at a relatively low cost. However, as observed in the present case, titration of the immunohistochemical condition of TFE3 is extremely difficult in order to exclude the possibility of a pseudo-positive reaction with the native TFE3 protein even with appropriate positive controls in place. Furthermore, even if the tumor shows negative immunoreactivity for TFE3, Xp 11.2 translocation RCC cannot be negated, as several pseudo-negative cases have been reported.
Therefore, translocation or gene fusion should be ascertained using fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) for correct diagnosis of Xp 11.2 translocation RCC. However, both of the above-mentioned genetic tests are expensive and are not yet covered by insurance in Japan. Moreover, performing RT-PCR with a formalin-fixed paraffin embedded (FFPE) specimen is often challenging due to low RNA quality, and, taking into account the cost and other technical reasons, these tests cannot be performed routinely in most institutions. As a result, many institutions in Japan diagnose Xp 11.2 translocation RCC without confirmatory genetic testing.
It is essential to develop a low-cost and easy-to-use technique for detecting Xp 11.2 translocation RCC biomarkers to ensure correct diagnosis, even in developing countries, thereby bridging the gap between the rich and the poor.
Aiko Kurisaki-Arakawa and Tsuyoshi Saito as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Human Pathology, Juntendo University, Tokyo, Japan