What are other Names for this Test? (Equivalent Terms)
- Gene Mutation Analysis for Low-Grade Endometrial Stromal Sarcoma
- Molecular Testing for LG-ESS
- Test for Molecular Diagnosis of Low-Grade Endometrial Stromal Sarcoma
What is Molecular Testing for Low-Grade Endometrial Stromal Sarcoma? (Background Information)
- Molecular Testing for Low-Grade Endometrial Stromal Sarcoma is a genetic test that is helpful in aiding a diagnosis of low-grade endometrial stromal sarcoma. The lab test results may also be subsequently useful in taking appropriate treatment decisions
- Low-grade endometrial stromal sarcoma (LG-ESS) is a type of endometrial stromal sarcoma, which is a malignant tumor of the uterus. It is mostly present in adult women, and both pre- and post- menopausal women may be affected
- The signs and symptoms of low-grade endometrial stromal sarcoma include unusual vaginal bleeding, abdominal pain, and sensation of pressure in the pelvic area. The complications are dependent upon the stage of the cancer and the method of treatment employed. Advanced stage tumors are observed to metastasize to the lung and ovary
The cause of LG-ESS is due to genetic mutations. Currently, studies indicate the following genetic defects:
- JAZF1-SUZ12(JJAZ1) fusion gene due to chromosomal translocation t(7;17)(p21;q15)
- EPC1-PHF1 fusion gene
- Other abnormalities seen include:
- t(6;7)(p21;p15), t(6;10;10)(p21;q22;p11), and t(1;6)(p34;p21)
- All these (above) are known to cause PHF1-JAZF1, EPC1-PHF1, and MEAF6-PHF1 gene fusion defects
The above genetic abnormalities can be detected using molecular studies, which may play a significant role in identifying the tumor type, and in some cases, helping the healthcare provider take appropriate treatment decisions.
The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:
- In situ hybridization technique, such as fluorescence in situ hybridization (FISH)
- Immunohistochemistry (IHC)
- Next-generation sequencing (NGS)
- Polymerase chain reaction (PCR)
- Comparative genomic hybridization (CGH)
- Karyotyping including spectral karyotyping
- mRNA analysis
- Tissue microarrays (TMAs)
- Southern blot test
- Northern blot test
- Western blot test
- Eastern blot test
The methodology used for low-grade endometrial stromal sarcoma may vary from one laboratory to another.
Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.
What are the Clinical Indications for performing the Molecular Testing for Low-Grade Endometrial Stromal Sarcoma Test?
Molecular Testing for Low-Grade Endometrial Stromal Sarcoma is undertaken in the following situations:
- To assist (and in some cases, confirm) the initial diagnosis of low-grade endometrial stromal sarcoma
- To distinguish other tumors/conditions that have similar histological features, when examined by a pathologist under the microscope
- To help in determining treatment options
- To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)
How is the Specimen Collected for Molecular Testing for Low-Grade Endometrial Stromal Sarcoma?
Following is the specimen collection process for Molecular Testing for Low-Grade Endometrial Stromal Sarcoma:
The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.
- Sample required:
- Fresh tumor tissue during biopsy
- Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
- Unstained tissue slides
- Process of obtaining the sample: As outlined by the laboratory testing facility
- Preparation required: As outlined by the laboratory testing facility
- In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
- Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
- Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
- Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tumor specimen over time
Cost of Molecular Testing for Low-Grade Endometrial Stromal Sarcoma:
- The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
- In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)
What is the Significance of the Molecular Testing for Low-Grade Endometrial Stromal Sarcoma Result?
The significance of Molecular Testing for Low-Grade Endometrial Stromal Sarcoma is explained:
- Presence of a positive test result helps aid, and in some cases, confirm the diagnosis of low-grade endometrial stromal sarcoma
- The result can help exclude other tumors with similar histological features
- It can help determine the prognosis of the patient
- In some cases, the test results may help in taking treatment decisions
The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.
Additional and Relevant Useful Information:
- Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test
- Additional mutations are still being discovered in many of these tumors. This may further contribute towards tumor diagnosis and treatment. Please consult with your healthcare provider for any information updates
Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.
What are some Useful Resources for Additional Information?
Please visit our Laboratory Procedures Center for more physician-approved health information:
References and Information Sources used for the Article:
https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 03/07/2017)
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 03/07/2017)
http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 03/07/2017)
http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 03/07/2017)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385272/ (accessed on 03/18/2017)
https://www.cancer.org/cancer/uterine-sarcoma/about/what-is-uterine-sarcoma.html (accessed on 03/18/2017)
https://www.hindawi.com/journals/sarcoma/2010/353679/ (accessed on 03/18/2017)
https://radiopaedia.org/articles/endometrial-stromal-tumours-1 (accessed on 03/18/2017)
Helpful Peer-Reviewed Medical Articles:
Carrano, A. V., et al. Measurement and purification of human chromosomes by flow cytometry and sorting. Proceedings of the National Academy of Sciences 76, 1382–1384 (1979)
Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)
Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)
Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17
Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524
Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368
Nucci, M. R., Harburger, D., Koontz, J., Dal Cin, P., & Sklar, J. (2007). Molecular analysis of the JAZF1-JJAZ1 gene fusion by RT-PCR and fluorescence in situ hybridization in endometrial stromal neoplasms. The American journal of surgical pathology, 31(1), 65-70.
Halbwedl, I., Ullmann, R., Kremser, M. L., Man, Y. G., Isadi-Moud, N., Lax, S., ... & Moinfar, F. (2005). Chromosomal alterations in low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma as detected by comparative genomic hybridization. Gynecologic oncology, 97(2), 582-587.
Balleine, R. L., Earls, P. J., Webster, L. R., Mote, P. A., Harnett, P. R., & Clarke, C. L. (2004). Expression of progesterone receptor A and B isoforms in low-grade endometrial stromal sarcoma. International journal of gynecological pathology, 23(2), 138-144.
Park, J. Y., Kim, D. Y., Kim, J. H., Kim, Y. M., Kim, Y. T., & Nam, J. H. (2011). The impact of tumor morcellation during surgery on the outcomes of patients with apparently early low-grade endometrial stromal sarcoma of the uterus. Annals of surgical oncology, 18(12), 3453-3461.
Ohta, Y., Suzuki, T., Omatsu, M., Hamatani, S., Shiokawa, A., Kushima, M., & Ota, H. (2010). Transition from low-grade endometrial stromal sarcoma to high-grade endometrial stromal sarcoma. International Journal of Gynecological Pathology, 29(4), 374-377.
Bartosch, C., Exposito, M., & Lopes, J. M. (2009). Low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma: a comparative analysis emphasizing the importance of distinguishing between these two groups. International journal of surgical pathology.
Dewaele, B., Przybyl, J., Quattrone, A., Finalet Ferreiro, J., Vanspauwen, V., Geerdens, E., ... & Sciot, R. (2014). Identification of a novel, recurrent MBTD1‐CXorf67 fusion in low‐grade endometrial stromal sarcoma. International journal of cancer, 134(5), 1112-1122.
Hrzenjak, A., Moinfar, F., Tavassoli, F. A., Kremser, M. L., Zatloukal, K., & Denk, H. (2005). JAZF1/JJAZ1 gene fusion in endometrial stromal sarcomas: molecular analysis by reverse transcriptase-polymerase chain reaction optimized for paraffin-embedded tissue. The Journal of Molecular Diagnostics, 7(3), 388-395.
Sciallis, A. P., Bedroske, P. P., Schoolmeester, J. K., Sukov, W. R., Keeney, G. L., Hodge, J. C., & Bell, D. A. (2014). High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features. The American journal of surgical pathology, 38(9), 1161-1172.