Mutation of the INI1 gene in composite rhabdoid tumor of the endometrium

Abstract

Composite rhabdoid tumors are typically adult tumors that contain a component of rhabdoid cells, which are characteristic of the aggressive childhood malignant rhabdoid tumor. Pediatric rhabdoid tumors are characterized by the inactivation of the hSNF5/INI1/SMARCB1 gene, with subsequent loss of expression of the protein. In contrast, only a single composite rhabdoid tumor has demonstrated involvement of the INI1 gene. In our study, INI1 protein expression was studied in 2 uterine carcinosarcomas with rhabdoid components (composite rhabdoid tumors). The rhabdoid component of 1 tumor showed lack of immunoreactivity for the INI1 protein and strong positivity for cyclin D1, whereas the adenocarcinomatous component of the tumor and both components of the second tumor were immunoreactive for the INI1 protein and negative for cyclin D1. Loss of one INI1 allele and a mutation in exon 7 of the remaining allele were detected in the first tumor, consistent with the immunohistochemistry results. Our results demonstrate that deletions and mutations of the INI1 gene can occur also in rare composite rhabdoid tumors of adulthood. Further studies are necessary, however, to determine the prognostic significance of this finding.

Figure 1

Case 1 -- Note abrupt transition of adenocarcinoma and rhabdoid tumor components (A). Rhabdoid tumor component (B), its negativity for INI1 protein (C) and strong positivity for cyclin D1 (D).

Figure 2

Case 2 -- Note abrupt transition between adenocarcinoma and rhabdoid tumor components (A). Rhabdoid component (B), its expression of INI1 protein (C) and lack of overexpression of cyclin D1 (D).

Figure 3

Interphase FISH of the rhabdoid component from case 1. The INI1 probe is labeled in red, and is present in one copy. The control probe (green) from the EWS locus in 22q12 is also deleted, consistent with monosomy 22.

Figure 4

Mutation of the INI1 gene in case 1. A deletion of one guanine in either codon 316 or 317 causes a frameshift, and the introduction of a novel stop codon after amino acid 318.