Histone Deacetylase 8 (HDAC8)

Histone deacetylases (HDACs) are a large family of enzymes originally identified as key regulators of nucleosomal histone acetylation, thereby controlling gene transcription. Specific HDACs have also been shown to deacetylate non-histone proteins (including tumor suppressor p53 and the cytoskeletal protein a-tubulin), indicating that these enzymes may be involved in the regulation of other processes. HDAC8, a class I HDAC, has a mainly cytosolic distribution and is exclusively expressed by cells showing smooth muscle differentiation, including visceral and vascular smooth muscle cells, myoepithelial cells, and myofibroblasts. HDAC8 associates with SMA and may regulate smooth muscle cytoskeleton dynamics².

Immunohistochemical expression (cytoplasmic)

Non-neoplastic tissues:

• Smooth muscle:

  • Small intestinal and colonic muscularis mucosae and muscularis propria²

  • Muscular layer of renal pelvis, ureter and bladder, vas deferens and epididymis periductal layer²

  • Myometrium, cervical stroma and Fallopian tube muscle²

  • Vascular smooth muscle^1,2

  • Skin erector pili smooth muscle²

• Myofibroblasts²

  • Lung alveolar septal myofibroblasts²

  • Subepithelial myofibroblasts in lamina propria of the gastrointestinal tract²

  • Prostatic stromal cells²

  • Testis peritubular myoid cells²

  • Ovarian external theca cells²

• Myoepithelial cells²

  • Tracheal, bronchial and bronchiolar myoepithelial cells from mucous glands²

  • Salivary glands myoepithelial cells²

  • Myoepithelial cells of sweat glands²

  • Mammary gland myoepithelial cells of lobules and ducts ²

It is not expressed by:

• Myocardium²

• Skeletal muscle²

• Endometrial stroma¹

• Nervous system (spinal cord, peripheral nerves and brain)²

• Bone²

In uterine tumours:

		HDAC8	Desmin	h-Caldesmon	SMA	Smooth muscle myosin	CD10
	Leiomyoma	15/15 (strong staining of more than 90% of tumour cells)1	15/151	15/151	15/151	15/151	6/151
	Highly cellular leiomyoma	8/91	9/91	9/91	9/91	9/91	4/91
	Epithelioid smooth muscle tumour	8/81	2/81	1/81	4/81	3/81	0/81
	Leiomyosarcoma	11/131	10/131	12/131	12/131	10/131	5/131
	Conventional endometrial stromal tumour	0/91	3/91	0/91	3/91	0/91	6/91
	Endometrial stromal tumour with sex cord differentiation	0/31	0/31	0/31	1/31	0/31	3/31
	Endometrial stromal tumour with smooth muscle differentiation	5/5 (staining confined to areas of smooth muscle differentiation)1	3/5 (staining in both areas of conventional endometrial stromal tumour and areas of smooth muscle differentiation)1	3/5 (staining confined to areas of smooth muscle differentiation)1	3/5 (staining in both areas of conventional endometrial stromal tumour and areas of smooth muscle differentiation)1	3/5 (staining confined to areas of smooth muscle differentiation)1	5/5 (staining in both areas of conventional endometrial stromal tumour [4 cases] and areas of smooth muscle differentiation [5 cases])1

Diagnostic utility

• Differentiation of uterine smooth muscle tumours from endometrial stromal tumours. HDAC8 may be a more sensitive marker than desmin and h-caldesmon in epithelioid smooth muscle tumours¹.

References

¹ de Leval L, Waltregny D, Boniver J, et al. Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus. Am J Surg Pathol 2006; 30:319-27

² Waltregny D, De Leval L, Glenisson W, et al. Expression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues. Am J Pathol 2004; 165:553-64 FULL TEXT

This page last revised 10.4.2006.

©SMUHT/PW Bishop