OCT4 (POU5F1, OTF3, OCT3)

OCT4 is a POU-domain transcription factor. It is present on chromosome 6p21.3. Oct4 maintains pluropotentiality. It is detectable in embryonic stem and germ cells but downregulated in all differentiated somatic cell types⁵. It binds transcription sites through octamer motifs, including that for fibroblast growth factor 4 and platelet-derived growth factor a receptor³. Knockout of the gene is lethal in mice². Staining is nuclear.

Immunohistochemical expression

• Undifferentiated pluripotent cells

• Germ cells of the ovary and testis, but not resting oocytes. It is not expressed by brain, heart, liver, spleen, skeletal muscle, lung, kidney or pancreas⁴.

• Germ cell tumours:

	Testicular tumours		OCT4
	Carcinoma in situ		positive2
	Mixed germ cell tumour (64 cases1), containing various combinations of components	seminoma	51/51 (all showed strong (3+) staining)1, 49/492
		embryonal carcinoma	54/54 (all but one case showed strong (3+) staining)1, positive2
		yolk sac tumour	0/381, negative2
		mature teratoma	0/311, negative2
		immature teratoma	0/201, negative2
		choriocarcinoma	0/151, negative2
	Spermatocytic seminoma		0/51, negative2
	Leydig cell tumour		0/81
	Sertoli cell tumour		0/61
	Unclassified sex cord stromal tumour		0/41
	Adenomatoid tumour		0/21
	Testicular tumour of adrenogenital syndrome		0/11
	Granulosa cell tumour		0/11
	Ovarian tumours
	Germ cell tumour	Ovarian dysgerminoma	2/22, 35/35 (strong diffuse positivity: 32 primary and 3 metastatic tumours: syncytiotrophoblastic cells were negative)4
		Gonadoblastoma	1/12, 2/2 (positive in the germ cell component: the sex cord components were negative)4
		Mature teratoma	0/144
		Yolk sac tumour	0/44
		Embryonal carcinoma	no data4
	Leydig cell tumour		0/14
	Sertoli cell tumour		0/14
	Sertoli-Leydig cell tumour		0/134
	Granulosa cell tumour	Adult type	0/134
		Juvenile type	0/94
	Brenner tumour		0/34
	Carcinoid tumour		0/44
	Struma ovarii		0/24
	Fibroma		0/54
	Thecoma		0/14
	Clear cell adenocarcinoma		4/14 (four cases showed staining of <10% of cells)4
	Serous adenocarcinoma		0/54
	Endometrioid adenocarcinoma		0/44
	Small cell carcinoma, hypercalcaemic type		0/64
	Stromal sarcoma		0/14
	Lymphoma	Diffuse large B-cell type	0/24
		Burkitt's	0/34
		Small cleaved B-cell type	0/14
	Metastatic malignant melanoma		0/14
	Metastatic carcinoid		0/24
	Metastatic small cell carcinoma		0/14
	Metastatic lobular carcinoma of the breast		0/14
	Non-gonadal tumours
	CNS	germinoma	25/25 (staining intense in 22 cases, absent from the teratomatous component of one case of mixed germ cell tumour. PLAP was positive in 23 of 25 cases.)5
		glioblastoma multiforme	0/105
		lymphoma	0/45
		pineoblastoma	0/35
		metastatic malignant melanoma	0/45
		capillary haemangioma	0/105
		pituitary adenoma	0/55
		meningioma	0/45
		Schwannoma	0/45
		metastatic carcinoma	0/5 (2 lung, 2 colon, 1 breast)5
	non-testicular tumour microarray of 3439 tumours2, all non-gonadal tumours negative, except:	Pulmonary squamous cell carcinoma	1/502
		Pulmonary large cell carcinoma	1/472
		Renal clear cell carcinoma	1/502

Diagnostic utility

• diagnosis of seminoma, CNS germinoma, ovarian dysgerminoma⁴ and embryonal carcinoma.

  • the ovarian tumours that form the differential for dysgerminoma are negative. Clear cell carcinoma may be positive, but occurs in older women.

• possibly in the differentiation of ovarian clear cell carcinoma from yolk sac tumour, endometrioid of serous carcinoma⁴.

• identification of a germ cell element, differentiating gonadoblastoma from pure sex cord stromal tumours.

References

¹Jones, T. D., T. M. Ulbright, et al. (2004). "OCT4 Staining in Testicular Tumors: A Sensitive and Specific Marker for Seminoma and Embryonal Carcinoma." Am J Surg Pathol 28(7): 935-40.

²Looijenga, L. H., H. Stoop, et al. (2003). "POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors." Cancer Res 63(9): 2244-50. FULL TEXT AVAILABLE ON LINE.

³Palumbo, C., K. van Roozendaal, et al. (2002). "Expression of the PDGF alpha-receptor 1.5 kb transcript, OCT-4, and c-KIT in human normal and malignant tissues. Implications for the early diagnosis of testicular germ cell tumours and for our understanding of regulatory mechanisms." J Pathol 196(4): 467-77.

⁴Cheng, L., A. Thomas, et al. (2004). "OCT4: a novel biomarker for dysgerminoma of the ovary." Am J Surg Pathol 28(10): 1341-6.

⁵Hattab EM, Tu PH, Wilson JD,Cheng L OCT4 Immunohistochemistry Is Superior to Placental Alkaline Phosphatase (PLAP) in the Diagnosis of Central Nervous System Germinoma. Am J Surg Pathol 2005; 29:368-371

This page last revised 18.3.2005.

©SMUHT/PW Bishop