Myogenin and Myo-D1

Myo-D1, myogenin, MRF4 (also called herculin or myf-6) and myf-5 are members of the Myo-D family of transcription factors and are responsible for initiating striated muscle differentiation. Myf-5 and MRF4 are expressed at specific limited periods in myogenesis. MyoD1 and myogenin are downregulated at birth. MRF4 is the dominant myogenic regulatory factor in adult skeletal muscle.

Antigen retrieval is required. Staining with My-D1 may become weaker if sections are stored for a few days after cutting². Staining for both antigens is lost with mercury-based fixatives such as B5². Staining is strictly nuclear. Myogenin produces staining that is clearly localised to the nucleus. Myo-D1 may sometimes also show cytoplasmic staining, making the nuclear staining more difficult to discern, but it is the nuclear staining that is significant². In rhabdomyosarcomas, both antigens may persist within areas of necrosis².

Immunohistochemical expression

• skeletal muscle

• lymph nodes may show rare myogenin-positive benign nuclei².

Myogenin has been detected in:

• strongly expressed in alveolar rhabdomyosarcoma and to a lesser extent in other rhabdomyosarcomas.

• some cases of fibromatosis¹

• some cases of infantile myofibromatosis¹

• some cases of synovial sarcoma¹

• some cases of leiomyosarcoma¹

Myo-D1 is preferentially expressed over myogenin in:

• alveolar rhabdomyosarcoma

• sclerosing rhabdomyosarcoma

		Myogenin	MyoD1	Desmin
	Alveolar rhabdomyosarcoma	97/100 (more than 50% of cells positive; 72 cases, 10% to 50% of cells positive; 18 cases, less than 10% of cells positive; 4 cases, minimal/focal staining; 3 cases.)2	97/99 (more than 50% of cells positive; 63 cases, 10% to 50% of cells positive; 24 cases, less than 10% of cells positive; 6 cases, minimal/focal staining; 4 cases.)2	positive in 99% of cases (the paper does not give precise figures for each subtype)2
	Embryonal rhabdomyosarcoma	96/99 (more than 50% of cells positive; 42 cases, 10% to 50% of cells positive; 38 cases, less than 10% of cells positive; 13 cases, minimal/focal staining; 3 cases.)2	97/100 (more than 50% of cells positive; 16 cases, 10% to 50% of cells positive; 58 cases, less than 10% of cells positive; 19 cases, minimal/focal staining; 4 cases.)2
	Rhabdomyosarcoma NOS	89/100 (more than 50% of cells positive; 48 cases, 10% to 50% of cells positive; 7 cases, less than 10% of cells positive; 15 cases, minimal/focal staining; 19 cases.)2	86/100 (more than 50% of cells positive; 18 cases, 10% to 50% of cells positive; 43 cases, less than 10% of cells positive; 18 cases, minimal/focal staining; 7 cases.)2
	Ewings/PNET	0/122	0/122	0/122
	Pleuropulmonary blastoma	8/9 (the positivity is in scattered rhabdomyoblasts)2	8/9 (the positivity is in scattered rhabdomyoblasts)2	8/92
	Haemopoietic	0/52	0/52	0/52
	Inflammatory myofibroblastic tumour	0/62	0/62	6/62
	Rhabdoid tumour	0/52	0/52	3/52
	Synovial sarcoma	0/42	0/42	0/42
	Sarcoma NOS	0/42	0/42	0/42
	Undifferentiated embryonal sarcoma of liver	0/42	0/42	2/42
	Epithelioid sarcoma	0/32	0/32	2/32
	Fibrosarcoma	0/22	0/22	1/22
	MFH	0/22	0/22	1/22
	Angiomatoid fibrous histiocytoma	0/12	0/12	0/12
	Angiomyofibroblastoma	0/12	0/12	1/12
	Fibrous hamartoma of infancy	0/12	0/12
	Mesenchymal hamartoma	0/12	0/12	1/12
	Fibromatosis	0/12	0/12	0/12
	Epithelioid MPNST	0/12	0/12	0/12
	Alveolar soft part sarcoma	0/12	0/12	1/12
	Langerhans cell histiocytosis	0/12	0/12	0/12
	Germ cell tumour with ERMS	1/12	1/12	1/12
	Sertoli-Leydig cell tumour	0/12	0/12	1/12
	Osteosarcoma	0/12	0/12	0/12

Both myogenin and Myo-D1 show more intense staining of alveolar rhabdomyosarcoma (ARMS) than they do of embryonal rhabdomyosarcoma (ERMS) or rhabdomyosarcoma NOS². With myogenin, ARMS shows diffuse staining while ERMS tends to show patchy staining.

Diagnostic utility

• Identification of skeletal muscle differentiation. Diagnosis of rhabdomyosarcoma.

References

Diagnostic Immunohistochemistry edited by Professor D. J. Dabbs, page 69.

¹ Montgomery, E., Goldblum, J.R. and Fisher, C. Leiomyosarcoma of the head and neck: a clinicopathological study. Histopathology 2002;40:518-25.

² Morotti RA, Nicol KK, Parham DM, et al. An Immunohistochemical Algorithm to Facilitate Diagnosis and Subtyping of Rhabdomyosarcoma: The Children's Oncology Group Experience. Am J Surg Pathol 2006; 30:962-968

This page last revised 20.8.2006.

©SMUHT/PW Bishop