Indication - Cancer
Basic panel of immunohistochemical (IHC) markers for diagnosis of solid tumours
IHC testing markers include desmin, cytokeratin, AE1/AE3, S100, synaptophysin, myogenin, hCG, PLAP, Oct3/4, NANOG, CD30, CD117/c-kit, WT1, SALL4
First added in 2019
Changed in 2020
Aid to diagnosis, Prognosis
To aid in diagnosis, prognosis and treatment of solid tumours, especially childhood cancer
Formalin-fixed paraffin-embedded tissue (FFPE)
WHO prequalified or recommended products
WHO supporting documents
WHO classification of tumours, 4th edition https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours; WHO list of priority medical devices for cancer management https://apps.who.int/iris/bitstream/handle/10665/255262/9789241565462-eng.pdf; WHO Guide for establishing a pathology laboratory in the context of cancer control. https://www.who.int/publications/i/item/guide-for-establishing-a-pathology-laboratory-in-the-context-of-cancer-control
ICD11 code: 2D4Z
Summary of evidence evaluation
IHC is the reference standard for classification thus no studies of the accuracy of the approach are available. Some evidence provided supported stepwise testing using a restricted batch of antibodies as an efficient testing process.
Summary of SAGE IVD deliberations
The basic panel of IHC stains is applicable in the clinical and pathological diagnosis of solid malignancies in a resource-sparing algorithm for settings with limited diagnostic tools or molecular testing. The panel is clinically useful for classification of solid tumours for prognosis and treatment of paediatric and adult solid malignancies. The panel should be considered a starting-point for the diagnosis of solid tumours, to which other antigens will be added, as appropriate.
SAGE IVD recommendation
The SAGE IVD recommended inclusion on the EDL of the basic panel of IHC tests for the diagnosis of solid tumours (to be used only in tertiary level). The Group noted that the panel is to be extended in future submissions.
Details of submission from 2020
Disease condition and impact on patients: The global cancer burden is estimated to have risen to 18.1 million new cases and 9.6 million deaths in 2018. One in five men and one in six women worldwide develop cancer during their lifetime, and one in eight men and one in 11 women die from the disease. Does this test meet a medical need? The test is for diagnosis of paediatric and adult solid tumours and for clinically useful sub-classification for prognosis and treatment, including HIV-associated and defining conditions. The panel is a minimum panel for diagnosis of solid tumours. The work incorporates and builds on that of the Global Initiative for Childhood Cancer and should be considered a starting-point for the diagnosis of solid tumours, upon which to build future applications. How the test is used: The panel is intended for laboratory use in qualitative identification of the antigens by IHC in formalin-fixed paraffin-embedded human tissues.
Public health relevance
Prevalence: Worldwide, the total number of people who are alive within 5 years of a cancer diagnosis is estimated to be 43.8 million. Socioeconomic impact: The economic impact of cancer is significant; in 2010, the total annual economic cost of cancer was estimated at approximately US$ 1.16 trillion, threatening economies at all income levels as well as causing financial catastrophe for individuals and families.
WHO or other clinical guidelines relevant to the test
WHO classification of tumours (1) and WHO list of priority medical devices for cancer management (2).
Evidence for clinical usefulness and impact
These tests are used routinely worldwide for detailed typing of malignant tumour tissue for classification and further management. The basic panel is intended as a resource-sparing strategy for making a definitive diagnosis (e.g. epithelial or non- epithelial) and orienting treatment (e.g. Ewing sarcoma or osteosarcoma). The IHC may be affected by procedural inefficiency, some of which is expected and can be controlled (3). The most common causes of false-negative immunostaining are poor tissue fixation, over-diluted or improperly optimized antibodies and epitope retrieval methods not optimized for individual antibodies. The clinical value of the panel of five antibodies has not been evaluated in a published paper, although it has been identified as a basic requirement in LMICs by expert pathologists working in global oncology, including the stakeholders of the WHO Global Initiative on Childhood Cancer. Studies of the clinical accuracy of single antibodies and evidence of the impact of the tests in clinical practice indicate that the basic panel allows diagnostic evaluation of soft tissue sarcomas such as rhabdomyosarcoma, leiomyosarcoma, Ewing sarcoma, other primitive neuroectodermal tumours, desmoplastic small round cell tumours, sarcomatoid carcinoma (and other cytokeratin-positive malignancies), melanoma, nerve sheath tumours, Wilms tumour, neuroblastoma, neuroendocrine carcinoma and other carcinomas (4–6). The treatment of these epithelial and non-epithelial cancers is distinct. The panel allows more accurate tumour tissue typing and therefore better tumour management and longer survival.
Evidence for economic impact and/or cost–effectiveness
The estimated average cost of an IHC test with five antibodies in LMICs is US$ 10–20 per slide (7). Use of the kit requires a laboratory technician for incubation and staining on an automatic stainer and a trained pathologist to read the slides and interpret the results.
Ethical issues, equity and human rights issues
Consent is required to obtain a tissue sample. The availability of a marker to define the nature and origin of paediatric solid tumours makes it possible to tailor treatment. Knowledge of the exact histology of cancers is recommended in the principal clinical guidelines for treatment, including multimodal approaches, sensitivity to chemotherapeutic agents and targeted agents. Microscopic histology cannot precisely identify the cancer type in some cases or its epithelial or non- epithelial origin, reducing the possibility of multimodal, integrated, tailored histology-driven therapy for children who have no access to or cannot afford IHC tests.
1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO classification of tumours, revised 4th edition, Vol. 2, WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: international Agency for Research on Cancer; 2017 (http://publications. iarc.fr/Book-And-Report-Series/Who-Iarc-Classification-Of-Tumours/Who-Classification-Of- Tumours-Of-Haematopoietic-And-Lymphoid-Tissues-2017, accessed May 2019). 2. WHO list of priority medical devices for cancer management. Geneva: World Health Organization; 2017 (http://www.who.int/medical_devices/publications/priority_med_dev_cancer_ management/en/, accessed May 2019). 3. Gown AM. Diagnostic immunohistochemistry: What can go wrong and how to prevent it. Arch Pathol Lab Med. 2016;140(9):893–8. 4. Fanburg-Smith JC, Miettinen M. Angiomatoid “malignant” fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype. Hum Pathol. 1999;30(11): 1336–43. 5. Folpe AL, McKenney JK, Bridge JA, Weiss SW. Sclerosing rhabdomyosarcoma in adults: report of four cases of a hyalinizing, matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma, chondrosarcoma, or angiosarcoma. Am J Surg Pathol. 2002;26(9):1175–83. 6. Oliva E, Young RH, Amin MB, Clement PB. An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies. Am J Surg Pathol. 2002;26(4):403–12. 7. Ch’ng ES, Khiro FI. Letter to Editor. Low cost immunohistochemistry bench for developing countries. Malaysian J Pathol. 2018;40(2):209–11.