Calretinin
Calretinin
is a 29 kD calcium-binding protein and a member of the family to EF-hand
proteins, to which S-100 also belongs.
Its function is thought to be to buffer intracellular calcium.
Immunohistochemical expression
Normal
tissues:
central and peripheral
nervous system: neurones and nerve fibres9
retina
mesothelium9
the keratinising superficial
layer of the pilar infundibulum9
eccrine glands9
the convoluted tubules
of the kidneys9
Leydig and Sertoli cells
of testes and the epithelium of the rete testis9
endometrium, stronger
in the secretory phase9
myometrial mast cells9
ovarian surface epithelium,
stromal and thecal cells, follicular cysts2, corpora lutea2
and the rete ovary9
adrenal cortex9
keratinising epithelial
cells of the thymus9
adipocytes9
Tumours:
Mesothelioma, but less commonly in carcinoma. The
antibody from Zymed, against human recombinant calretinin, appears
to give superior discrimination.
|
conclusion regarding
usefulness |
adenocarcinoma |
mesothelioma |
Doglioni
19969 (Polyclonal,
variously Swant and Chemicon) |
yes |
28/294 |
44/44(36
epithelioid, 5 biphasic and 3 sarcomatoid) |
Gotzos
199610 (Polyclonal,
non-commercial) |
yes |
0/4(The
only immunoreactivity was the rare weak staining of vacuolated
cells.) |
22/23(Immunoreactivity
was seen in epithelial mesotheliomas (7/7) and in the epithelial
component of mixed mesotheliomas(15/15). The one negative case
appears to have been a purely sarcomatoid mesothelioma.) |
Riera
199713 (Polyclonal,
Chemicon) |
no |
13/221 |
24/57 |
Ordonez
199814 (Polyclonal,
Zymed) |
yes |
14/155(3/38
pulmonary, 5/38 ovarian, 2/15 endometrial, 2/23 breast, 2/16 colonic,
0/8 renal, 0/8 prostatic, 0/6 thyroid, 0/3 pancreatic) |
38/38 |
Leers
199815 (Polyclonal,
Swant) |
yes |
1/21(one
case showed positivity of less than 10% of cells) |
20/20(17
cases showed positivity of more than 10% of cells, 3 cases showed
positivity of less than 10% of cells) |
Cury
20008 (Polyclonal,
Zymed) |
yes |
1/59(One
case showed nuclear staining. lung = 19; breast = 21; ovary =
6; colon = 10; kidney = 4; uterus, epididymis, pancreas = 1 case
each) |
47/51(all
epithelioid mesotheliomas) |
Brockstedt
20004 (Polyclonal,
Zymed) |
yes |
16/57 |
110/119(Staining
is described as "nuclear and cytoplasmic".) |
Oates
200024 (Polyclonal,
Chemicon) |
no |
28/40 |
25/26 |
Kayser
20015 (Polyclonal,
Dako) |
yes |
20/146(9/82
lung, 8/47 breast, 0/3 colon, 1/2 kidney, 2/12 site not known) |
97/118(84/99
epithelioid, 9/12 mixed and 4/7 sarcomatoid) |
Carella
20017 (Polyclonal,
Chemicon) |
yes |
2/20 |
40/46(The
staining is stated to be "finely granular and cytoplasmic.
and the nuclei always remained unstained.") |
Comin
200112 (Polyclonal,
Swant) |
yes |
2/23 |
42/42 |
Miettinin
200129 (Polyclonal,
Zymed) |
|
|
30/30(123
epithelioid, 7 sarcomatous mesotheliomas) |
Foster
200125 (Polyclonal,
Chemicon) |
no |
35/51(lung
adenocarcinomas: greater tahn 50% staining in 23 cases) |
35/67(greater
than 50% staining in 30 cases) |
Foster
200125 (Polyclonal,
Zymed) |
? |
9/15 |
3/15 |
Roberts
200126 (Polyclonal,
Chemicon) |
no |
8/18 |
44/112 |
Tot
200127 (Polyclonal,
Zymed) |
yes |
0/37(various
sites of origin) |
13/14 |
Miettinin
200321 |
|
31/255(17/148
acinar type, differentiated, 8/48 acinar type, solid, poorly differentiated
, mucin-positive, 0/13 bronchoalveolar, 3/22 acinar type with
focal neuroendocrine differentiation, 3/18 adenocarcinoma, neuroendocrine) |
27/28(10
of 10 tubulopapillary, 6 of 6 combined tubulopapillary and poorly
differentiated and 11 of 12 poorly differentiated solid epithelial
tumours) |
Abutaily
20023 (Polyclonal,
Zymed) |
yes |
2/35(cytoplasmic
and nuclear) |
33/41(positivity
seen in 11/11 epithelioid, 20/23 mixed and 2/7 sarcomatoid mesotheliomas) |
Ordonez
200328 (Polyclonal,
Zymed) |
yes |
4/50(lung
adenocarcinomas, in 2 cases <1% of cells stained, in 2 cases,
1-25% of cells stained) |
60/60(epithelioid
mesotheliomas: in 45 cases >75% of cells stained, in 15 cases
50-75% of cells stained) |
Overall |
YES |
14% (204/1486) |
80% (751/936) |
A systematic
review of seventeen studies (consisting of 885 epithelioid
mesotheliomas and 912 pulmonary adenocarcinomas) reported sensitivities
and specificities of calretinin for epithelioid mesothelioma of
82% and 85%39.
There are some controversy as to whether there is nuclear
as well as cytoplasmic staining in mesothelioma, and which component
is diagnostically reliable. Staining is reportedly weaker in post mortem
specimens that in the corresponding ante mortem specimens from the same
patients19.
Similar studies have been done on cytological material:
|
conclusion regarding
usefulness |
adenocarcinoma |
mesothelioma |
Barberis
199730 (Polyclonal,
Swant) |
yes |
3/13(various
sites of origin) |
8/8 |
Simsir
199931 (Polyclonal,
Chemicon) |
no |
9/29(various
sites of origin) |
15/26 |
Chhieng
200032 (Polyclonal,
Zymed) |
yes |
0/21(various
sites of origin) |
14/16 |
Wieczorek
200033 (Polyclonal,
Zymed) |
yes |
3/39(various
sites of origin) |
26/29 |
Davidson
200134 (Polyclonal,
Swant) |
yes |
3/98(various
sites of origin) |
11/12 |
Simsir
200135 (Polyclonal,
Zymed) |
yes |
2/15(sites
of origin not stated)
|
15/17 |
Overall |
YES |
9% (20/215) |
82% (89/108) |
Most studies have been of mesothelioma versus pulmonary
adenocarcinoma. Some metastatic carcinomas, such as renal
cell carcinoma, pose particular problems.
Calretinin positivity appears to be more common in colonic carcinomas,
particularly those that are poorly differentiated. Based on a total of
82 cases:
well-differentiated |
5% of cases20 |
|
moderately differentiated |
20% of cases20 |
poorly differentiated |
67% of cases20 |
overall |
22/5% of cases20 |
Most studies compare mesothelioma with pulmonary
adenocarcinoma. There are relatively few studies breaking down adenocarcinomas
by subtype, or of other types of pulmonary tumour. Where positive, staining
is typically both nuclear and cytoplasmic.
adenocarcinoma |
acinar type, differentiated |
17/148(9 cases showing >10%
of tumour cells positive, 8 cases showing less than 10% of tumour
cells positive.)21 |
acinar type, solid, poorly-differentiated,
mucin-positive |
8/48(5 cases showing >10%
of tumour cells positive, 3 cases showing less than 10% of tumour
cells positive)21 |
bronchoalveolar, mucinous |
0/6 21 |
bronchoalveolar, non-mucinous |
0/7 21 |
acinar with focal neuroendocrine
differentiation |
3/22(1 case showing >10%
of tumour cells positive, 2 cases showing less than 10% of tumour
cells positive) 21 |
neuroendocrine |
3/18(All 3 cases showing
less than 10% of tumour cells positive) 21 |
clear cell |
0/6 21 |
large cell |
NOS |
45/120(36 cases showing more
than 10% of tumour cells positive, 9 cases showing less than 10%
of tumour cells positive) 21, 0/814 |
with focal neuroendocrine differentiation |
1/10(less than 10% of tumour
cells positive) 21 |
neuroendocrine carcinoma |
15/33(8 cases showing more
than 10% of tumour cells positive, 7 cases showing less than 10%
of tumour cells positive) 21 |
small cell carcinoma |
20/41(15 cases showing more
than 10% of tumour cells positive, 5 cases showing less than 10%
of tumour cells positive.) 21 |
squamous cell |
keratinising |
21/62(4 cases showing more
than 10% of tumour cells positive, 17 cases showing less than
10% of tumour cells positive.) 21 |
non-keratinising |
19/62(10 cases showing more
than 10% of tumour cells positive, 10 cases showing less than
10% of tumour cells positive) 21 |
NOS |
11/2814 |
sarcomatoid carcinoma, spindle cell |
1/6(showing less than
10% of tumour cells positive) 21 |
giant cell carcinoma |
4/6(All 4 cases showing
more than 10% of tumour cells positive) 21 |
| |
adult granulosa cell tumour |
13/13diffuse strong; 9,
diffuse moderate;1, focal strong; 32,
35/35in
7 cases, only luteinised cells were positive17,
6/14used
protease rather than steam for antigen retrieval18 |
juvenile granulosa cell tumour |
4/4all diffuse strong2, 4/417 |
thecoma |
9/917 |
fibrothecoma |
10/11diffuse strong; 6,
diffuse moderate;2, diffuse weak; 1, focal moderate; 12, 14/1417,
0/8used
protease rather than steam for antigen retrieval18 |
Leydig
cell tumour |
3/3diffuse strong; 2,
diffuse moderate;1, focal strong; 1 !!!2 |
Sertoli
cell tumour |
4/417 |
Sertoli-Leydig cell tumour |
1/1diffuse strong; 12, 13/1317,
10/1018 |
sex cord-stromal tumour with annular
tubules |
2/2diffuse strong; 1,
diffuse weak;12 |
gynandroblastoma |
1/1diffuse strong; 12 |
sclerosing stromal tumour |
1/1diffuse strong; 12, 2/217 |
steroid cell |
3/317 |
sex-cord stromal tumour, unclassified |
1/1diffuse strong; 12, 3/317 |
sex
cord-stromal tumours, overall |
36/372, 87/8717 |
fibroma |
19/2017 |
adenofibroma (stromal component) |
6/917 |
fibrosarcoma |
8/817 |
serous carcinoma |
3/11<25% of cells staining17 |
atypical mucinous neoplasm |
6/19<25% of cells staining17 |
endometrioid adenocarcinoma |
2/6diffuse strong; 1,
moderate focal;12,
3/15<25%
of cells staining. Four with sex-cord-like elements all negative17 |
clear cell carcinoma |
1/7<25% of cells staining17 |
endometrial
stromal neoplasm |
1/7moderate focal;12 |
ovarian carcinoid tumour |
1/2diffuse weak;12 |
Brenner tumour |
3/4focal strong; 1, focal
weak; 22, 1/13epithelial
component only, 4+17 |
malignant mixed Mullerian tumour |
0/217 |
ovarian leiomyomatous tumour |
0/12 |
metastatic lobular carcinoma |
1/4focal weak; 12 |
lymphoma |
1/5focal weak; 12 |
testicular
seminoma |
1/4focal weak; 12 |
dysgerminoma |
0/717 |
yolk sac tumour |
0/517 |
choriocarcinoma |
0/117 |
embryonal carcinoma |
0/117 |
immature teratoma |
0/417 |
mixed germ cell tumour |
0/417 |
desmoplastic
small round cell tumour |
0/22 |
small cell carcinoma |
0/117 |
clear cell sarcoma |
0/117 |
female
adnexal tumour of probable Wolffian origin |
91% of 25 cases16 |
| |
|
Extra-ovarian tumours which may enter the differential of metastatic
granulosa cell tumour:
|
calretinin |
primary left atrial myxoma |
19/19 |
primary right atrial myxoma |
5/5 |
myxoma emboli |
1/1 |
mural thrombus |
0/10 |
jaw myxoma |
0/6 |
papillary fibroelastomas |
0/2 |
Other stromal tumours:
Diagnostic utility
References
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revised 16.2.2006.
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Bishop