Mesothelin

Monoclonal antibody MAb K1 recognizes a 40-kDa glycoprotein present on the surface of mesothelial cells, mesotheliomas, and ovarian cancers¹. The protein has been named mesothelin because it is made by mesothelial cells. Mesothelin may play a role in cellular adhesion. Serum mesothelin has potential for screening for mesothelioma in those exposed to asbestos, for the monitoirng of disease progression and as a target for immunotherapy⁵.

Immunohistochemical expression

• differentiation of mesotheliomas from adenocarcinomas

	adenocarcinoma	mesothelioma
Chang 19961	0/23 (pulmonary)	19/19 (epithelioid)
Miettinen2	134/256 (see details below)	25/28 (110 of 10 tubulopapillary, 6 of 6 combined tubulopapillary and poorly differentiated, 9 of 12 poorly differentiated)
Ordonez 20033	19/50 (all primary lung adenocarcinomas: 1 case >75% of cells stained, 5 cases 50-75% of cells, 5 cases 25-50% of cells and 8 cases 1-25% of cells)	60/60 (all epithelioid mesotheliomas: 28 case >75% of cells stained, 17 cases 50-75% of cells, 4 cases 25-50% of cells and 11 cases 1-25% of cells)
Galloway 20064	15/31 (All cases were chosen as metastatic to pleura. 15 were primary lung, 3 primary breast, 2 primary colon and 11 unknown primaries. Six showed weak diffuse, 7 strong diffuse and 2 focal staining.)	51/62 (positivity in 39/39 epithelioid, 6/15 desmoplastic/spindle cell, 8/8 biphasic at least in the epithelioid component. Staining was strong and diffuse in 31, weak and diffuse in 4, and focal in 16. In 11 cases, the staining was cytoplasmic)
Overall	47% (168/360)	92% (155/169)
Dennis 20056	18/396	3/66

Staining in mesothelioma is typically membranous, especially along the apical membrane³. Adenocarcinomas show variable pattern of positivity, including membranous^2,3. Positivity is common in serous carcinomas of the ovary and pancreatic adenocarcinomas³.

Most studies compare mesothelioma with adenocarcinoma. There are relatively few studies breaking down adenocarcinomas by subtype, or of other types of pulmonary tumour.

adenocarcinoma	acinar type, differentiated	78/148 (60 cases more than 10% of cells positive, 18 cases less than 10% of cells positive) 2
	acinar type, solid, poorly-differentiated, mucin-positive	30/49 (25 cases more than 10% of cells positive, 5 cases less than 10% of cells positive) 2
	bronchoalveolar, mucinous	3/6 (3 cases more than 10% of cells positive) 2
	bronchoalveolar, non-mucinous	5/7 (5 cases more than 10% of cells positive) 2
	acinar with focal neuroendocrine differentiation	10/22 (7 cases more than 10% of cells positive, 3 cases less than 10% of cells positive) 2
	neuroendocrine	4/18 (2 cases more than 10% of cells positive, 2 cases less than 10% of cells positive) 2
	clear cell	4/6 (2 cases more than 10% of cells positive, 2 cases less than 10% of cells positive) 2
large cell	NOS	15/118 (8 cases more than 10% of cells positive, 7 cases less than 10% of cells positive) 2
	with focal neuroendocrine differentiation	2/10 (2 cases less than 10% of cells positive) 2
	neuroendocrine carcinoma	6/33 (5 cases more than 10% of cells positive, 1 case less than 10% of cells positive) 2
small cell carcinoma		0/412, 0/36
squamous cell	NOS	0/76
	keratinising	10/62 (4 cases more than 10% of cells positive, 6 cases less than 10% of cells positive)2
	non-keratinising	19/62 (8 cases more than 10% of cells positive, 11 cases less than 10% of cells positive) 2
sarcomatoid carcinoma, spindle cell		0/6 2
giant cell carcinoma		2/6 (1 case more than 10% of cells positive, 1 case less than 10% of cells positive) 2

Non-pulmonary tumours:

	Breast carcinoma	1/356
	Ovarian serous	17/186
	Ovarian mucinous	3/106
	Endometrial	5/106
	Pancreas	25/536
	Ampulla of Vater	5/66
	Cholangiocarcinoma	7/106
	Gastric	7/346
	Oesophageal adenocarcinoma	4/216
	Oesophageal squamous cell carcinoma	0/76
	Colonic	1/476
	Prostatic	0/186
	Renal cell carcinoma	0/156
	Hepatocellular carcinoma	0/66

Diagnostic utility

• Differentiation of mesotheliomas from adenocarcinomas: mesothelin is of limited value due to the high rate of positivity in adenocarcinomas. Negativity is a strong indication against a diagnosis of mesothelioma.

References

¹ Chang, K. and Pastan, I. Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci U S A 1996;93:136-40.

² Miettinen, M. and Sarlomo-Rikala, M. Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura. Am J Surg Pathol 2003;27:150-8.

³ Ordonez, N. G. (2003). "The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma." Am J Surg Pathol 27(8): 1031-51.

⁴ Histopathology 2006;48:767.

⁵ Ordonez NG. Immunohistochemical diagnosis of epithelioid mesothelioma: an update. Arch Pathol Lab Med 2005; 129:1407-14 FULL TEXT

⁶ Dennis JL, Hvidsten TR, Wit EC, et al. Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm. Clin Cancer Res 2005; 11:3766-72 FULL TEXT

This page last revised 1.8.2006.

©SMUHT/PW Bishop