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STAT3d Mutation Analysis Test

Last updated May 29, 2017

The STAT3d Mutation Analysis Test detects abnormalities in the STAT3d gene. It aids in the diagnosis of HNSCC.

What are other Names for this Test? (Equivalent Terms)

  • Stat 3 Gene Mutation Analysis Test
  • STAT3D Mutation Analysis Test

What is STAT3d Mutation Analysis Test? (Background Information)

  • STAT3d mutation refers to an alteration in the STAT3d gene. It is associated with head and neck squamous cell carcinoma (HNSCC)
  • The STAT3d gene gives instructions for a protein called Stat 3. Stat 3 helps control the growth of division of mucous cells of the oral, nasal, sinus, and other tissues of the head and neck
  • Stat 3 regulates the growth of these tissue cells by responding to signals from outside the cell. These chemical signals - transforming growth factor (TGF) and epidermal growth factor (EGF) - are necessary for maintenance and development of tissues. They inform the cell to grow and divide
  • EGF and EGF are recognized by proteins of a signaling pathway called the TGF-a/EGFR pathway. This pathway then stimulates Stat 3 to activate growth and division
  • Stat 3 exerts its effects by changing the pattern of conversion of DNA to proteins. It is a transcription factor, meaning it affects the way genetic information is transcribed, or turned into RNA before being processed and made into proteins
  • Stat 3 is known to increase production of a crucial cell cycle protein called cyclin D1. Cyclin D1 increases the rate of growth and division of the cell and the formation of new blood vessels around the tissue. Thus, Stat 3 stimulates growth and division by increasing cyclin D1 levels
  • Alterations in the STAT3d gene may result in a Stat 3 protein that is defective. The defective Stat 3 protein is overactive and capable of increasing cyclin D1 levels independently of signals from the TGF-a/EGFR pathway
  • The result of Stat 3 hyperactivity resulting from a mutation in the STAT3d gene is the uncontrolled growth and division of the mucous cell, resulting in HNSCC
  • The STAT3d Mutation Analysis Test detects abnormalities in the STAT3d gene. It aids in the diagnosis of HNSCC. It also helps guide treatment by aiding in the selection of chemotherapy drugs

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 the test 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 STAT3d Mutation Analysis Test?

Following are the clinical indications for performing the STAT3d Mutation Analysis Test: 

  • A sore that does not heal; a sore that bleeds
  • A growth, lump, or thickening of the skin or lining in the mouth
  • Loose teeth
  • Poorly-fitting dentures
  • Tongue pain
  • Jaw pain or stiffness
  • Difficult or painful chewing
  • Difficult or painful swallowing
  • Sore throat

In general, the molecular genetic testing is undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis
  • 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 STAT3d Mutation Analysis Test?

Following is the specimen collection process for STAT3d Mutation Analysis Test

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 on which the test is performed may include:
    • 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 STAT3d Mutation Analysis Test:

  • 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 STAT3d Mutation Analysis Test Result?

  • The presence of a mutation in the STAT3d gene indicates a positive result for the STAT3d Mutation Analysis Test. This may point to a diagnosis of head and neck squamous cell carcinoma (HNSCC)

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:

  • Overproduction of cyclin D1 is found in over 50% of cases of head and neck squamous cell carcinoma (HNSCC). This is important because the Stat 3 protein, made from the instructions on the STAT3d gene, directly raises cyclin D1 levels
  • 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

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, 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 05/10/2017)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 05/10/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 05/10/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 05/10/2017)

Masuda, M. (2002). Constitutive Activation of Signal Transducers and Activators of Transcription 3 Correlates with Cyclin D1 Overexpression and May Provide a Novel Prognostic Marker in Head and Neck Squamous Cell Carcinoma. Cancer Research, 52(12).

Symptoms and causes - Mouth cancer - Mayo Clinic. (2016, October 21). Retrieved from http://www.mayoclinic.org/diseases-conditions/mouth-cancer/symptoms-causes/dxc-20157232

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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

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Nakajima, K., Yamanaka, Y., Nakae, K., Kojima, H., Ichiba, M., Kiuchi, N., ... & Hirano, T. (1996). A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. The EMBO journal, 15(14), 3651.

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Benkhart, E. M., Siedlar, M., Wedel, A., Werner, T., & Ziegler-Heitbrock, H. L. (2000). Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression. The journal of Immunology, 165(3), 1612-1617.

Bousquet, C., & Melmed, S. (1999). Critical role for STAT3 in murine pituitary adrenocorticotropin hormone leukemia inhibitory factor signaling. Journal of Biological Chemistry, 274(16), 10723-10730.

Lee, H., Herrmann, A., Deng, J. H., Kujawski, M., Niu, G., Li, Z., ... & Yu, H. (2009). Persistently activated Stat3 maintains constitutive NF-κB activity in tumors. Cancer cell, 15(4), 283-293.

Kamakura, S., Oishi, K., Yoshimatsu, T., Nakafuku, M., Masuyama, N., & Gotoh, Y. (2004). Hes binding to STAT3 mediates crosstalk between Notch and JAK–STAT signalling. Nature cell biology, 6(6), 547-554.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 29, 2017
Last updated: May 29, 2017