Immunohistochemistry and Fluorescence In Situ Hybridization for INI1 in Proximal Type Epithelioid Sarcoma and Malignant Extrarenal Rhabdoid Tumor.
Armita Bahrami, Susana Raimondi, Andrew Folpe. St. Jude Children's Research Hospital, Memphis, TN; Mayo Clinic, Rochester, MN
Background: INI1 is a tumor suppressor gene whose protein expression is known to be lost almost exclusively in certain tumors: epithelioid sarcomas (ES), malignant extrarenal rhabdoid tumors (MERT), and true rhabdoid tumors of central nervous system (ATRT) and kidney. Proximal-type ES (PTES) is a variant of ES with rhabdoid morphology, predilection for proximal extremities and more aggressive behavior than classical ES. Considerable debate exists as to whether PTES and MERT represent the same or different entities, and whether their frequency of INI1 abnormalities differs. We examined INI1 alteration and INI1 protein loss in a group of such tumors with the goal of identifying distinct clinicopathologic characteristics between those with and without INI1 aberrations.
Design: 8 cases previously coded as PTES, MERT, or ATRT were retrieved. All were immunostained for CK (OSCAR) and INI1, and a subset for CD34. FISH was conducted on FFPE tumor sections in all cases using a laboratory-developed dual-color probe containing INI1 [CTD-2511E13+CTD-2034E7](22q11.2) and PANX2 [RPCI3-402G11](22q13.33) as control.
Results: Table 1 summarizes the clinical, immunohistochemical and FISH findings. Although all cases showed loss of INI1 expression by immunohistochemistry, FISH analysis showed only 2 cases with INI1 deletion, 1 heterozygous and 1 homozygous. The ATRT was aneuploid for chromosome 22. There were no clinicopathologic features that distinguished cases with and without INI1 deletion.
Conclusions: The rare finding of homozygous INI1 deletion/mutation in our series supports the contention that other mechanisms, most likely through epigenetics and post-translational modifications, are responsible for suppression/inactivation of INI1 gene production in most such cases. Although our sample size is too small to draw a definitive conclusion, our initial findings do not suggest any specific clinicopathologic features unique to INI1 altered cases compared with those with only protein loss. The incidence of INI1 alteration and its value as a reliable indicator for stratification of such cases into prognostically relevant categories should be evaluated in larger studies with clinical outcome data.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 21, Tuesday Morning