Uterine leiomyomas, also known as fibroids, are a common yet poorly studied condition that primarily affects women during their reproductive years. It is estimated that up to 70% of white women and over 80% of women of African ancestry will be diagnosed with fibroids in their lifetime. This disease has significant implications for healthcare delivery and costs worldwide. While many women with fibroids do not experience symptoms, around 30% will have severe symptoms such as abnormal uterine bleeding, anemia, pelvic pain and pressure, back pain, urinary issues, constipation, or infertility, requiring treatment. Additionally, fibroids have been linked to poor pregnancy outcomes.

The widespread occurrence of fibroids significantly affects healthcare expenses globally. Research suggests that the annual costs associated with uterine fibroids, including direct and indirect expenses, can reach up to $34.4 billion in the United States. In other countries, hospital admissions related to fibroids contribute to substantial annual costs, such as $348 million in Germany, $120 million in France, and $86 million in England. These figures highlight the financial burden imposed by fibroids on healthcare systems worldwide.

Black women are diagnosed with fibroids, which are often multiple, larger, and more severe, earlier in life compared to other ethnicities. African-American women are notably more likely to undergo surgeries such as hysterectomy and myomectomy. There’s a suggestion that the racial disparity in fibroids incidence and behavior may be linked to genetic differences influencing estrogen biosynthesis or metabolism. Studies have identified potential genetic predispositions to fibroids, notably through a syndrome known as hereditary leiomyomatosis and renal cell carcinoma. This syndrome is associated with the fumarate hydratase gene, a tumor suppressor that leads to more than 5 fold increase risk of developing an aggressive form of kidney cancer. 

2SC staining, or immunohistochemistry for 2-succinocysteine (2SC), can be utilized on uterine fibroids to evaluate for Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) and fumarate hydratase (FH) deficiency. HLRCC is caused by mutations in the FH gene, leading to a loss of FH protein expression or function.

The staining technique involves applying specific antibodies against 2SC, which is a byproduct of the enzymatic reaction involving FH. In normal cells with intact FH function, the FH enzyme converts fumarate to malate, and 2SC is not produced. However, in cells lacking functional FH due to mutations, fumarate accumulates and reacts with cysteine, forming 2SC. Therefore, the presence of 2SC indicates FH deficiency.

By performing 2SC staining on uterine fibroid tissue samples, pathologists can assess the FH status of the fibroids. If FH deficiency is observed, it suggests the possibility of an underlying HLRCC-related genetic alteration. This information can guide further genetic testing and counseling for the individual and their family members.

It is important to note that while 2SC staining is a valuable tool for assessing FH deficiency, it should be used in conjunction with other diagnostic methods, such as genetic testing, to confirm the presence of FH mutations and establish an HLRCC diagnosis definitively. The combination of clinical evaluation, histopathological examination, and genetic analysis is crucial in the comprehensive assessment of HLRCC and FH deficiency in uterine fibroids.

1.) Giuliani E, As-Sanie S, Marsh EE. Epidemiology and management of uterine fibroids. Int J Gynaecol Obstet. 2020 Apr;149(1):3-9. doi: 10.1002/ijgo.13102. Epub 2020 Feb 17. PMID: 31960950.

2.) Joseph NM, Solomon DA, Frizzell N, Rabban JT, Zaloudek C, Garg K. Morphology and Immunohistochemistry for 2SC and FH Aid in Detection of Fumarate Hydratase Gene Aberrations in Uterine Leiomyomas From Young Patients. Am J Surg Pathol. 2015 Nov;39(11):1529-39. doi: 10.1097/PAS.0000000000000520. PMID: 26457356.