Here, we have presented the systematic review of patient characteristics, treatment details, and survival outcomes of patients with INI1-deficient tumor.
INI1is a member of a large protein complex involved in chromatin remodeling and thus regulation of gene expression[8]. INI1-deficient cancers are characterized by the biallelic loss of function in both INI1 alleles[5]. INI1 immunohistochemistry has emerged as a powerful diagnostic tool to identify INI1-altered neoplasms in routine surgical pathology practice[9, 10]. INI1 deficiency is observed as the genetic hallmark in virtually all MRT and in most cases of ES and PDC. In addition, subsets of myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, and epithelioid peripheral nerve sheath tumors are INI1-deficient[7, 11].
MRT, a rare tumor occurring almost exclusively in infants and young children, is caused by INI1 biallelic inactivation in virtually all cases[12]. MRT can occur in the kidney, central nervous system, or extracranial/extrarenal locations [10]. The tumors occur in infants and young children and confer a poor prognosis requiring aggressive therapeutic interventions to improve the chances for survival. In our study, patients with INI1-deficient non-MRT tumors had a more favorable 3-year OS of 88.9%±10.5% vs. 30.3%±9.2% for those with INI1-deficient MRT(p < 0.01). MRTs pose a diagnostic challenge, as they display heterogeneous histopathologic features and differentiate along multiple lineages. The identification of alterations in the INI1 gene in MRT using immunohistochemical staining has lead to improved diagnosis of MRT as well as the discovery of the loss of INI1 expression in some non-MRTs[13].
ES is a rare and aggressive soft-tissue sarcoma subtype, FISH analysis demonstrates INI1 genomic inactivation through homozygous deletion in 90% of epithelioid sarcomas[14], along with INI1 loss in 90% of cases, irrespective of histologic subtype. This tumor is cytokeratin and EMA positive, which can be mistaken for myoepithelial carcinoma (MEC) of soft tissue, ES expresses positivity for CD34 but negativity for myoepithelial markers and S100[15]. CD34 expression in > 50% of ES is helpful to rule out metastatic carcinoma and CD34 immunostaining can be helpful, as this marker is positive in about half of ES and is typically negative in MRTK in Proximal ES[16]. Some authors realized that diagnostic utility of INI1 in cases with the exclusive composition of epithelioid tumor cells with CD34 negativity[17]. (MEC) of soft tissue, also known as malignant myoepithelial tumor, is an uncommon malignancy. Cytologic diagnosis of this entity is challenging due to its rarity and heterogeneous morphology. Wang L et al reported a case with MEC of soft tissue showed loss of INI-1 expression[18].
PDC, a rare, aggressive tumor originating from notochordal tissue, shows loss of INI1 expression, which occurs in children and young adults, with a peak incidence at 1–29 years of age (median, 11 years)[19], An overview of the gene expression profiles from a spectrum of connective tissue tumors suggested that brachyury was uniquely expressed in chordomas, and almost all cases of chordoma including conventional and PDC showed brachyury immunoexpression.