Table of Contents
Definition / general | Essential features | Pathophysiology | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Sample pathology report | Board review style question #1 | Board review style answer #1Cite this page: Raza M, Ud Din N. FLI1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsFLI1.html. Accessed December 25th, 2024.
Definition / general
- FLI1 (Friend leukemia integration 1) gene is a proto-oncogene located on chromosome 11q24
Essential features
- Due to the increasing number of tumors found to express FLI1, more specific markers or molecular confirmation is necessary for the diagnosis of Ewing sarcoma
Pathophysiology
- Key member of the ETS family of transcription factors and closely related to ERG (Am J Respir Cell Mol Biol 2017;57:121)
- Crucial role in maintenance and differentiation of hematopoietic stem cells and angiogenesis
Interpretation
- Staining pattern: nuclear
- Interpretation: positive = staining of 10% of tumor cells (usually is > 50%) (Am J Surg Pathol 2001;25:1061)
Uses by pathologists
- To differentiate Ewing sarcoma from other round blue cell tumors
- 90% of Ewing sarcoma have EWS-FLI1 fusion
- Distinguish Ewing sarcoma of kidney (positive) from blastema predominant Wilms tumor (negative)
- Distinguish Ewing sarcoma (positive) from small cell osteosarcoma or mesenchymal chondrosarcoma (negative) (Appl Immunohistochem Mol Morphol 2011;19:233)
- Diagnosis of benign and malignant vascular tumors (positive) (Am J Surg Pathol 2001;25:1061)
Prognostic factors
- Overexpression in astrocytoma = poor prognosis (Oncotarget 2017;8:29174)
- Increased expression in nonsmall cell lung carcinoma = poor prognosis (Appl Immunohistochem Mol Morphol 2016;24:556)
- Overexpression in endometrial cancer = adverse prognosis (Cancer Invest 2015;33:469)
Microscopic (histologic) images
Positive staining - normal
- Endothelial cells, T and B lymphocytes
Positive staining - disease
- Ewing sarcoma / PNET
- Vascular tumors (94%) (Am J Surg Pathol 2001;25:1061)
- Astrocytomas (moderate to strong staining in 81%; grade II: 35%; grade III / IV: 87%) (Oncotarget 2017;8:29174)
- Lymphoblastic lymphoma (85%), variable for other lymphomas (Appl Immunohistochem Mol Morphol 2009;17:409)
- Melanoma (50%; strong staining in only 4%) (Histol Histopathol 2008;23:1309)
- Merkel cell carcinoma (90%) (Histopathology 2005;46:622)
- Epithelioid sarcoma (93%) (Mod Pathol 2014;27:496)
- Mesothelioma (95%) (Hum Pathol 2018;81:138)
Negative staining
- Desmoplastic small round cell tumor (Mod Pathol 2004;17:547)
- Blastema predominant Wilms tumor (Am J Surg Pathol 2002;26:320)
- Small cell osteosarcoma (Appl Immunohistochem Mol Morphol 2011;19:233)
- Germ cell tumors
- Muscle, nerve and fibroblasts
Sample pathology report
- Liver, left lobe mass, Trucut biopsy:
- Features are consistent with epithelioid hemangioendothelioma (see comment)
- Comment: Histological examination shows cores of a neoplasm composed of cords, clusters and small nests of round to polygonal cells. These cells have vesicular nuclei, conspicuous nucleoli and eosinophilic cytoplasm. Intracytoplasmic lumina are noted, occasionally containing red blood cells. The background is hyalinized with myxoid areas. Tumor cell are diffusely positive for CD31, CD34, ERG and FLI1 and focally positive for CK CAM5.2.
Board review style question #1
Discolored skin from left foot of a 70 year old Caucasian man was biopsied and shows compressed, slit-like vascular channels infiltrating dermis admixed with proliferation of moderately atypical, spindled cells. Which is the best immunohistochemical profile that confirms the diagnosis of Kaposi sarcoma?
- CD31 positive, CD34 positive, ERG positive
- ERG negative, HHV8 positive, EMA positive
- ERG positive, CD34 positive, FLI1 negative
- FLI1 positive, HHV8 positive, CD31 positive
- LMP1 positive, MOC31 negative, p63 positive
Board review style answer #1
D. FLI1 positive, HHV8 positive, CD31 positive. FLI1 is a highly sensitive vascular marker, while CD31 is both sensitive and specific, thus confirming the vascular origin. HHV8 positivity is seen in Kaposi sarcoma among vascular tumors.
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Reference: FLI1
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Reference: FLI1