FKBP12

FKBP12 is a cytosolic protein that binds FK506, thereby mediating the immunosuppressive effects of FK506. The FKBP12/FK506 complex binds and inactivates calneurin, a serine/threonine phosphatase. The inhibition of calneurin inhibits Ca²⁺ and calmodulin-dependent B and T cell responses, by blocking NFAT-mediated transcription. FKBP12 is also found in association with ryanodine receptors: ryanodine play a role in calcium release from endoplasmic and sarcoplasmic reticulum and has been identified in striated muscle and endothelial cells.

Immunohistochemical expression

The available antiserum is polyclonal. Staining may be cytoplasmic or nuclear.

Normal tissues:

• Hassall's corpuscles¹

• Epidermis¹

• Neurones¹

		FKBP12	CD31	CD34
	Vascular tumours:
	Papillary endothelial hyperplasia (Masson's lesion)	8/81	8/81	8/81
	Capillary haemangioma	9/91	9/91	9/91
	Kaposi's sarcoma	8/81	7/8 (7 cases positive, 1 case equivocal)1	8/81
	Epithelioid haemangioendothelioma	13/15 (13 cases positive, 1 case equivocal)1	12/15 (12 cases positive, 1 case equivocal)1	11/151
	Angiosarcoma	18/191	19/191	11/18 (11 cases positive, 1 case equivocal)1
	Total for vascular tumours (All 59 vascular tumours stained with at least one marker1)	56/591	55/591	47/581
	Non-vascular tumours, by tissue microarray:
	Squamous cell carcinoma of lung	1/161		1/311
	Adenocarcinoma of lung	1/341	1/341
	Squamous cell carcinoma of head and neck	1/281
	Adenocarcinoma NOS of head and neck	1/11	1/11
	Breast fibroadenoma			1/51
	Intraduct carcinoma of breast	0/54 (it is not clear how many of the cores in the microarrary were interpretable)1	0/54 (it is not clear how many of the cores in the microarrary were interpretable)1	0/54 (it is not clear how many of the cores in the microarrary were interpretable)1
	Ductal carcinoma of breast	0/143 (it is not clear how many of the cores in the microarrary were interpretable)1	2/931	0/143 (it is not clear how many of the cores in the microarrary were interpretable)1
	Lobular carcinoma of breast	1/81
	Gastric adenocarcinoma	1/341	1/241
	Colonic adenocarcinoma	0/87 (it is not clear how many of the cores in the microarrary were interpretable)1	1/691	1/711
	Cloacogenic anal carcinoma	1/21
	Hepatocellular carcinoma		1/141
	Conventional renal cell carcinoma	0/36 (it is not clear how many of the cores in the microarrary were interpretable)1	2/331	2/311
	Nephroblastoma		1/31
	Renal oncocytoma		1/11
	Transitional carcinoma of the bladder	0/25 (it is not clear how many of the cores in the microarrary were interpretable)1	0/25 (it is not clear how many of the cores in the microarrary were interpretable)1	0/25 (it is not clear how many of the cores in the microarrary were interpretable)1
	Prostatic carcinoma	23/781	5/781
	Ovarian carcinoma	0/44 (it is not clear how many of the cores in the microarrary were interpretable)1	1/371	0/44 (it is not clear how many of the cores in the microarrary were interpretable)1
	Endometrial carcinoma	0/26 (it is not clear how many of the cores in the microarrary were interpretable)1	0/26 (it is not clear how many of the cores in the microarrary were interpretable)1	0/26 (it is not clear how many of the cores in the microarrary were interpretable)1
	Uterine clear cell carcinoma			1/11
	Papillary thyroid carcinoma	0/20 (it is not clear how many of the cores in the microarrary were interpretable)1	0/20 (it is not clear how many of the cores in the microarrary were interpretable)1	4/191
	Embryonal sarcoma			1/21
	Adrenocortical carcinoma	2/41	1/41
	Melanoma	1/191
	Rosai-Dorfmann disease		2/21
	Small lymphocytic lymphoma		2/61
	Follicular lymphoma	1/21
	Multiple myeloma		1/11
	DLBCL	0/36 (it is not clear how many of the cores in the microarrary were interpretable)1		0/36 (it is not clear how many of the cores in the microarrary were interpretable)1
	Mediastinal large cell lymphoma		1/111
	Large cell lymphoma of spleen		2/111
	Lymphoblastic lymphoma			2/41
	Peripheral T cell lymphoma		1/31
	Colonic T cell lymphoma		1/11
	Cutaneous T cell lymphoma		1/11
	Post transplant lymphoma		1/11
	Mast cell disease		1/11
	Solitary fibrous tumour	2/31		3/31
	Gastrointestinal stromal tumour			6/101
	Hibernoma	1/11	1/11
	Liposarcoma			4/91
	Myxoid liposarcoma		2/81
	Leiomyosarcoma			5/101
	MPNST			3/51
	Malignant fibrous histiocytoma			3/111
	Giant cell MFH		3/111
	Alveolar soft part sarcoma			2/21
	Total for non-vascular tumours	39/11011	42/10171	39/11011

Diagnostic utility

Potentially, the identification of vascular tumours, as part of a panel with CD31 and CD34.

References

¹Higgins JP, Montgomery K, Wang L, et al. Expression of FKBP12 in benign and malignant vascular endothelium: an immunohistochemical study on conventional sections and tissue microarrays. Am J Surg Pathol 2003; 27:58-64

This page last revised 6.4.2005.

©SMUHT/PW Bishop