Test Id : SCCA

Collection Container/Tube: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 0.5 mL

Collection Information: Centrifuge and aliquot serum into a plastic vial. Do not submit in original tube.

0.2 mL

Aiding in the evaluation and monitoring of squamous cell carcinoma of the head and neck, lung, and cervix

This test should not be used to screen for carcinoma or other disorders including those of the liver, lung, or skin.

Squamous cell carcinoma (SCC) of the skin is the second most common form of skin cancer, characterized by abnormal, accelerated cellular growth. SCC antigen (SCCA) represents a subfraction of tumor-associated antigens related to squamous cell carcinoma and is used as a serum tumor marker for squamous cell carcinoma of the head and neck, lung (including esophagus), and other types of SCC. Additionally, associations between serum SCCA concentrations and tumor stage, size, and progression have been observed in SCCs of the cervix and esophagus. SCC is the most common histological type of cervical cancer, accounting for more than 70% of cervical cancer cases in the United States.

SCCA is a cytoplasmic glycoprotein found in normal squamous epithelia and elevated concentrations in serum from patients with SCCs. SCCA exists as two isoforms, SCCA1 and SCCA2, which are 91% identical at the amino acid level. Total SCCA assays (which measure both SCCA 1 and 2), like this assay, may be used in conjunction with clinical evaluation in the follow-up/monitoring of patients with SCC of the cervix, lung, head and neck, and esophagus.

SCCA serum concentrations may be used for monitoring response to treatment in patients with cervical cancer. Notably, in 46% to 92% of patients who experience recurrence, an elevated level of SCCA after treatment was observed before the clinical manifestation of relapse, with a median lead time of 2 to 8 months. While pretreatment serum SCCA concentrations in patients with cervical cancer are more correlated with tumor burden and prognosis, there is some evidence that it may also help to differentiate patients with and without risk for lymph node metastasis. Furthermore, it has been shown that SCCA is a useful marker in follow-up and therapy monitoring, and increasing SCCA levels may predict relapse.

Increased serum SCCA values have also been associated with benign inflammatory diseases, including various skin disorders, such as psoriasis and atopic dermatitis, in addition to inflammatory disorders, such as asthma. In one report, 70% of patients with psoriasis and dermatitis had SCCA concentrations greater than 2.4 ng/mL (radioimmunoassay reference value), with some patients having SCCA concentrations between 20 and 60 ng/mL. Another study found that median concentrations of SCCA2 were higher in psoriasis (2.7 ng/mL, interquartile range: 1.25-7.75 ng/mL) than in controls (0.7 ng/mL, interquartile range: 0.40-0.80 ng/mL).

Males: < or =2.00 mcg/L

Females: < or =1.67 mcg/L

Reference values have not been established for patients younger than 18 years old.

Squamous cell carcinoma antigen (SCCA) concentrations alone should not be interpreted as evidence of the presence or absence of malignancy. Although the sensitivity of this assay for the presence of squamous cell carcinoma (SCC) is not ideal, SCCA remains one of the few clinically viable potential circulating markers used for the detection and monitoring of SCC. Previous estimates of sensitivity are 20% to 53% for lung SCC(1,2) and 38% for tonsil and tongue SCC.(3) In a previous study, SCCA was elevated (>2 ng/ml) in 21.6% of untreated cervical squamous cell carcinomas.(4) Serum levels of SCCA in cervical cancer were significantly related to tumor stage, size, and depth of infiltration(5) and may also serve as a prognostic predictor of overall outcome.(6)

SCCA is expressed in normal epithelial tissues and may be elevated in nonmalignant conditions such as tuberculosis, sarcoidosis, eczema, erythroderma, and psoriasis. Psoriasis, in particular, is known to exhibit elevated SCCA concentrations. Additionally, serum concentrations of squamous cell carcinoma antigen have been reported to be elevated in severe cases of atopic dermatitis and asthma. Although there are conflicting reports, SCCA has been shown to be elevated in hepatocellular carcinoma (HCC) and may serve as a potential marker of HCC. A study of 961 patients (HCC, n =499)(7) indicated that at a serum SCCA cut-off of 3.8 ng/mL, sensitivity was 42% with a specificity of 83% for patients with HCC.

This Brahms Kryptor total SCCA assay detects both SCCA1 and SCCA2 antigen isoforms with a 90% and 72% measured recovery, respectively.

Do not interpret serum squamous cell carcinoma antigen (SCCA) concentrations as absolute evidence of the presence or the absence of malignant disease. Use serum SCCA results in conjunction with information from the clinical evaluation of the patient and other diagnostic procedures.

Elevated concentrations may also occur in cases of kidney insufficiency, skin disorders such as psoriasis, or inflammatory lung disease such as asthma.

Specimens with extremely elevated SCCA concentrations (>2200 mcg/L) have the potential to exhibit a "hook effect" and appear to have markedly lower SCCA concentrations in the absence of specimen dilution.

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.

SCCA concentration determinations are method dependent. Values obtained with different assay methods or kits may be different and cannot be used interchangeably.

1. Fischbach W, Rink C: SCC-Antigen: ein sensitiver und spezifischer Tumormarker fur Plattenepithelkarzinome? [SCC antigen: a sensitive and specific tumor marker for squamous cell carcinoma?]. Dtsch Med Wochenschr. 1988 Feb 26;113(8):289-293. doi: 10.1055/s-2008-1067632

2. Tas F, Aydiner A, Topuz E, Yasasever V, Karadeniz A, Saip P: Utility of the serum tumor markers: CYFRA 21.1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC) in squamous cell lung cancer. J Exp Clin Cancer Res. 2000 Dec;19(4):477-481

3. Fischbach W, Meyer T, Barthel K: Squamous cell carcinoma antigen in the diagnosis and treatment follow-up of oral and facial squamous cell carcinoma. Cancer. 1990 Mar 15;65(6):1321-1324

4. Bolger BS, Dabbas M, Lopes A, Monaghan JM: Prognostic value of preoperative squamous cell carcinoma antigen level in patients surgically treated for cervical carcinoma. Gynecol Oncol. 1997 May;65(2):309-313

5. Gaarenstroom KN, Kenter GG, Bonfrer JM, et al: Can initial serum cyfra 21-1, SCC antigen, and TPA levels in squamous cell cervical cancer predict lymph node metastases or prognosis? Gynecol Oncol. 2000 Apr;77(1):164-170. doi: 10.1006/gyno.2000.5732

6. Liu Z, Shi H: Prognostic role of squamous cell carcinoma antigen in cervical cancer: A meta-analysis. Dis Markers. 2019 Jun 2;2019:6710352. doi: 10.1155/2019/6710352

7. Giannelli G, Marinosci F, Sgarra C, Lupo L, Dentico P, Antonaci S: Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma. Int J Cancer. 2005 Sep 10;116(4):579-583. doi: 10.1002/ijc.20847

8. Bae SN, Namkoong SE, Jung JK, et al: Prognostic significance of pretreatment squamous cell carcinoma antigen and carcinoembryonic antigen in squamous cell carcinoma of the uterine cervix. Gynecol Oncol. 1997 Mar;64(3):418-424

9. Beale G, Chattopadhyay D, Gray J, et al: AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease. BMC Cancer. 2008 Jul;8:200. doi: 10.1186/1471-2407-8-200

10. Duk JM, van Voorst Vader PC, ten Hoor KA, Hollema H, Doeglas HM, de Bruijn HW: Elevated levels of squamous cell carcinoma antigen in patients with a benign disease of the skin. Cancer. 1989 Oct 15;64(8):1652-1656. doi: 10.1002/1097-0142(19891015)64:8<1652::aid-cncr2820640816>3.0.co;2-m

11. Watanabe Y, Yamaguchi Y, Komitsu N, et al: Elevation of serum squamous cell carcinoma antigen 2 in patients with psoriasis: associations with disease severity and response to the treatment. Br J Dermatol. 2016 Jun;174(6):1327-1336. doi: 10.1111/bjd.14426

12. Mitsuishi K, Nakamura T, Sakata Y, et al: The squamous cell carcinoma antigens as relevant biomarkers of atopic dermatitis. Clin Exp Allergy. 2005 Oct;35(10):1327-33. doi: 10.1111/j.1365-2222.2005.02353.x

13. Ohta S, Shibata R, Nakao Y, et al: The usefulness of combined measurements of squamous cell carcinoma antigens 1 and 2 in diagnosing atopic dermatitis. Ann Clin Biochem. 2012 May;49(Pt 3):277-284. doi: 10.1258/acb.2011.011065

14. Liu Y, Cao Y, He S, Cai W. Technical and clinical performance of two methods to detect squamous cell carcinoma antigen levels for comparing pathological diagnosis coincidence rates in lung, cervical, and head and neck cancers. Clin Lab. 2020 Jul 1;66(7). doi: 10.7754/Clin.Lab.2019.190912

15. Zhou Z, Li W, Zhang F, Hu K: The value of squamous cell carcinoma antigen (SCCa) to determine the lymph nodal metastasis in cervical cancer: A meta-analysis and literature review. PLoS One. 2017 Dec 11;12(12):e0186165

16. Zheng NN, Zhang RC, Yang XX, Tao YK, Zhong LS: Squamous cell carcinoma antigen is useful in the differential diagnosis of erythroderma. Int J Derm. 2019 Aug;58(8):e158-e159. doi: 10.1111/ijd.14498

Squamous cell carcinoma antigen is measured by homogeneous automated immunofluorescent assay on the BRAHMS Kryptor Compact PLUS. The Kryptor Compact PLUS uses time resolved amplified cryptate emission (TRACE) technology based on a nonradioactive transfer of energy. This transfer occurs between two-fluorescent tracers: the donor (europium cryptate) and the acceptor (Alexa Fluor 647). In the squamous cell carcinoma antigen assay, an anti-SCC monoclonal mouse antibody is labeled with europium cryptate, and an anti-SCC mouse monoclonal antibody is labeled with Alexa Fluor 647. Squamous cell carcinoma antigen is sandwiched between the two antibodies, bringing them into close proximity. When the antigen-antibody complex is excited with a nitrogen laser at 337 nm, some fluorescent energy is emitted at 620 nm, and the rest is transferred to Alexa Fluor 647. This energy is then emitted as fluorescence at 647 nm. A ratio of the energy emitted at 647 nm to that emitted at 620 nm (internal reference) is calculated for each sample. Signal intensity is proportional to the number of antigen-antibody complexes formed and, therefore, to antigen concentration.(Unpublished Mayo method)

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This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

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