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 monitoring of disease
progression and as a target for immunotherapy5.
Immunohistochemical expression
|
adenocarcinoma |
mesothelioma |
Hang 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 membranous2,3.
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 |
| |
|
Mesothelin has been assayed by ELISA in
pleural effusions:
| |
Site |
Diagnosis
|
Pleural fluid mesothelin mean concentration, nM |
|
| Pleura |
Mesothelioma |
Epithelioid |
57.2(Number
of cases: 11, interquartile range: 41.7-73.1) 7, 46.9(Number
of cases: 15, Standard Error of the Mean: 1.1) 8, 72.7(Number of cases: 31,
interquartile range: 29.3-108.8) 11 |
| Biphasic |
38.8(Number
of cases: 4, interquartile range: 5.1-85.7) 7, 30.1(Number of cases: 5,
Standard Error of the Mean: 0.8) 8, 10.5(Number
of cases: 6, interquartile range: 6-32.9) 11 |
| Sarcomatoid |
16.0(Number
of cases: 5, interquartile range: 3.6-24.0) 7, 4.5(Number of cases: 9,
Standard Error of the Mean: 1.4) 8
, 5.96(Number
of cases: 4, interquartile range: 1.12-8.02) 11 |
| unknown (cytology only) |
38.5(Number
of cases: 4, interquartile range: 25.7-87.4) 7, 39.2(Number of cases: 23,
Standard Error of the Mean: 1.0) 8
|
| All |
40.3(Number
of cases: 24, interquartile range: 18.3-68.1) 7,27.7(Number of cases: 52,
Standard Error of the Mean: 1.3) 8, 65.6(Number
of cases: 45, Standard error of the mean: 11.3, range: 0-255)9, 46.1(Number of cases: 43,
interquartile range: 11.5-94.7) 11 |
| Non-malignant |
transudate |
4(Number
of cases: 35, Standard Error of the Mean: 0.7) 8 |
| Congestive cardiac failure |
4.7(interquartile
range: 0.0-12.8) 7 |
| non-infective exudate |
4.3(Number
of cases: 30, Standard Error of the Mean:0.9 ) 8 |
| fibrinous pleurisy |
12.8(interquartile
range: 7.2-15.0) 7 |
| infective exudate |
4.3(Number
of cases: 19, Standard Error of the Mean: 0.9) 8 |
| empyema |
0.0(interquartile
range: 0.0-1.5) 7 |
| benign pleural disease associated with asbestos exposure |
6.4(Number
of cases: 21, interquartile range: 0.55-11.3) 11 |
| various |
19.0(Number
of cases: 30, Standard error of the mean: 7.5, range: 0-151)9 |
| Non-mesotheliomatous malignancy |
lung |
6.0(interquartile
range: 0.8-12.3) 7 |
| breast |
4.0(interquartile
range: 0.0-12.5) 7 |
| GI |
7.9(interquartile
range: 4.2-16.6) 7 |
| unknown primary |
42.5(interquartile
range: 27.9-76.9) 7 |
various |
6.3(Number
of cases: 56, Standard Error of the Mean: 1.2) 8, 27.5(Number of cases: 20,
Standard error of the mean: 11.25, range: 0-140)9, 6.4(Number of cases: 28,
interquartile range: 0.53-22.3) 11 |
| Peritoneal |
Mesothelioma |
48.0(Number
of cases: 7, Standard Error of the Mean: 0.9) 8 |
| Ovarian carcinoma |
73.7(Number
of cases: 4, Standard Error of the Mean: 0.8) 8 |
| Other non-mesotheliomatous malignancy |
3.6(Number
of cases: 10, Standard Error of the Mean: 0.7) 8 |
| Non-malignant |
liver disease |
3.0(Number
of cases: 6, Standard Error of the Mean: 0.6) 8 |
| dialysis fluid |
0.2(Number
of cases: 15, Standard Error of the Mean: 1.1) 8 |
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Pleural fluid mesothelin at
cut off of 20 nM |
Specificity |
Sensitivity |
|
| all mesothelioma versus non-malignancy |
98%8 |
67%8 |
| mesothelioma excluding sarcomatoid versus non-malignancy |
82%7, 98%8 |
77%8 |
| all mesothelioma versus other malignancy and non-malignancy |
90%7 , 86%8, 84%(cut
off 20.8 nM)11 |
71%7, 65%(cut
off 20.8 nM)11 |
| all malignancies versus non-malignancy |
97%7 |
33%7 |
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.
Pleural fluid mesothelin levels quantified by ELISA
have been proposed as being indicative of the diagnosis of mesothelioma
with a cut-off value of 20 nM7,8,9,10.
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 Galloway
ML, Murray D, Moffat DF. The use of the monoclonal antibody mesothelin
in the diagnosis of malignant mesothelioma in pleural biopsies. Histopathology.
2006 May;48(6):767-9.
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
7 Davies
HE, Sadler RS, Bielsa S, Maskell NA, Rahman NM, Davies RJ, et al. Clinical
impact and reliability of pleural fluid mesothelin in undiagnosed pleural
effusions. Am J Respir Crit Care Med. 2009 Sep 1;180(5):437-44
8 Creaney
J, Yeoman D, Naumoff LK, Hof M, Segal A, Musk AW, et al. Soluble mesothelin
in effusions: a useful tool for the diagnosis of malignant mesothelioma.
Thorax. 2007 62(7):569-76.
9 Pass
HI, Wali A, Tang N, Ivanova A, Ivanov S, Harbut M, et al. Soluble mesothelin-related
peptide level elevation in mesothelioma serum and pleural effusions. Ann
Thorac Surg. 2008 Jan;85(1):265-72
10 Lee
YC. Hunting for a pleural fluid test for mesothelioma: is soluble mesothelin
the answer? Thorax. 2007 Jul;62(7):561-2.
11 Scherpereel
A, Grigoriu B, Conti M, Gey T, Gregoire M, Copin MC, et al. Soluble mesothelin-related
peptides in the diagnosis of malignant pleural mesothelioma. Am J Respir
Crit Care Med. 2006 May 15;173(10):1155-60.
This
page last revised 18.9.2009.
©SMUHT/PW
Bishop