CK
5/6
Immunohistochemical expression
See Cytokeratins in normal epithelia
and specific
cytokeratins in common carcinomas.
basal cells of bronchial
epithelium and of prostatic glands6
squamous
cell carcinoma5 and
large cell carcinoma
of lung5: adenocarcinoma
of the lung is generally negative6.
transitional cell carcinoma5
mesothelium and mesothelioma
is frequently
positive: by comparison, adenocarcinomas are much less often positive.
Initially K5 was suggested as a marker for mesothelioma. The antibody
AE14 against K5 reacted with 12 of 13 mesothelioma but none of 21
pulmonary adenocarcinomas in cryostat sections7.
In the absence of antibodies specific for CK5 and effective on formalin-fixed
paraffin-embedded tissues, a monoclonal antibody against both CK5
and CK6 has been used:
|
adenocarcinoma |
mesothelioma |
Clover
19974 |
5/27(lung
adenocarcinomas. Staining in 4 cases was equivocal) |
23/23 |
Ordonez
19985 |
14/123(0/30
lung adenocarcinomas, 10/30 ovarian, 2/10 endometrioid, 1/18 breast,
1/7 thyroid, 0/10 kidney, 0/10 colonic, 0/8 prostate. Staining
was weak and focal.) |
40/40 |
Cury
20001 |
9/63(lung
= 19; breast = 21; ovary = 6; colon = 10; kidney = 4; uterus,
epididymis, pancreas = 1 case each) |
56/61 |
Kayser
2001(It
is not clear whether these results are for cytokeratin 5 or cytokeratin
5/6)2 |
72/146(33/82
lung, 27/47 breast, 1/3 colon, 1/2 kidney, 10/12 site not known) |
90/118(74/99
epithelioid, 10/12 mixed and 6/7 sarcomatoid) |
Carella
20013 |
1/20(the
positive case was an adenosquamous carcinoma) |
40/46(included
all histological types) |
Atanoos
200110 |
not
studied |
51/92(included
6 small cell mesotheliomas) |
Kaufmann11 |
30/141(various
sites of origin) |
14/14 |
Miettinen
200110 |
not
studied |
22/30(21/23
epithelioid, 1/7 sarcomatoid) |
Tot
2001 |
6/79(various
sites of origin) |
9/14 |
Abutaily
20029 |
2/35(lung
adenocarcinomas: staining in two cases was both cytoplasmic and
membranous) |
26/41(19
cases membranous and cytoplasmic, 7 cases cytoplasmic only:
|
Chu
200215 |
1/21(lung
adenocarcinomas) |
13/17(all
biphasic mesotheliomas) |
Miettinen
20038 |
25/254 |
26/28(10
of 10 tubulopapillary, 5 of 6 combined tubulopapillary and poorly
differentiated, 11 of 12 poorly differentiated) |
Ordonez
200313 |
1/50(lung
adenocarcinomas: 1 case showed positivity of 5% of tumour cells,
possibly in association with squamous differentiation)
|
60/60(all
epithelioid mesotheliomas: 32 cases >75% of cells, 16 cases
50-75% of cells, 7 cases 25-50% of cells, 3 cases 1-25% of cells,
2 cases <1% of cells) |
Overall |
17% (166/959) |
80% (470/584) |
A systematic
review of eight studies (consisting of
402
epithelioid
mesotheliomas and 402 pulmonary adenocarcinomas) reported sensitivities
and specificities of CK5/6 for
epithelioid mesothelioma of 83% and 85%16.
Most studies compare mesothelioma with pulmonary
adenocarcinoma. There are relatively few studies breaking down pulmonary
adenocarcinomas by subtype, or of other types of pulmonary tumour.
adenocarcinoma |
acinar
type, differentiated |
17/146(8
cases more than 10% of cells staining, 9 cases less than 10% of
cells staining) 8 |
acinar
type, solid, poorly-differentiated, mucin-positive |
7/49(7
cases more than 10% of cells staining) 8 |
bronchoalveolar,
mucinous |
0/6 8 |
bronchoalveolar,
non-mucinous |
1/7(1
case less than 10% of cells staining) 8 |
acinar
with focal neuroendocrine differentiation |
0/22 8 |
neuroendocrine |
0/18 8 |
clear
cell |
0/6 8 |
NOS |
3/2914, 1/11(using
antibody to CK5)17 |
large
cell |
NOS |
67/120(53
cases more than 10% of cells staining, 14 cases less than 10%
of cells staining) 8,
1/9(using
antibody to CK5)17 |
with
focal neuroendocrine differentiation |
3/10(2
cases more than 10% of cells staining, 1 cases less than 10% of
cells staining) 8 |
neuroendocrine
carcinoma |
6/33(5
cases more than 10% of cells staining, 1 cases less than 10% of
cells staining) 8 |
small
cell carcinoma |
11/41(4
cases more than 10% of cells staining, 7 cases less than 10% of
cells staining) 8,
0/1515, 2/13(using antibody to
CK5)17 |
squamous
cell |
keratinising |
62/62(61
cases more than 10% of cells staining, 1 cases less than 10% of
cells staining) 8 |
non-keratinising |
54/62(47
cases more than 10% of cells staining, 7 cases less than 10% of
cells staining) 8 |
NOS |
27/36(23
cases showed staining of >25% of tumour cells)14, 12/12(using
antibody to CK5)17 |
sarcomatoid
carcinoma, spindle cell |
1/6(1
case less than 10% of cells staining) 8 |
giant
cell carcinoma |
3/6(2
cases more than 10% of cells staining, 1 cases less than 10% of
cells staining) 8 |
poorly
differentiated carcinoma |
1/314 |
carcinoid |
1/1015 |
| |
Some metastatic carcinomas, such as renal
cell carcinoma, pose particular problems.
Extra-pulmonary tumours:
| |
Adenocarcinomas are
mostly negative: |
stomach |
0/1515 |
|
colon |
0/1612,
3/5314, 0/2015 |
cholangiocarcinoma |
2/1415 |
pancreas |
5/1315 |
kidney |
0/912,
0/1915 |
breast |
1/512,
14/63(11/55
invasive ductal carcinomas, 2/7 invasive lobular carcinoma, 1/1
ductal carcinoma in situ) 14,
8/2615 |
uterus |
1/312,
5/10(endometrioid
carcinomas)15 |
ovary |
1/212,
12/4414, 6/2415 |
prostate |
7/6414,
0/1815 |
thyroid |
0/212 |
| |
|
|
squamous carcinomas |
25/25(of skin and mucosae)15 |
basal cell carcinoma of skin |
20/2015 |
hepatocellular carcinoma |
1/2815 |
thymoma |
8/815 |
salivary gland, all types |
26/2815 |
thyroid, all types |
0/5415 |
transitional cell carcinoma of bladder |
15/2415 |
undifferentiated carcinoma, multiple
sites |
2/2715 |
adrenocortical tumour |
0/2015 |
germ cell tumour |
0/1415 |
epithelioid sarcoma of soft tissue |
0/1215 |
synovial sarcoma |
0/615 |
| |
|
| |
|
|
| |
|
|
Melanoma:
1/24(one
case showed staining of ~5% of cells)14
Glioblastoma: 0/2314
Diagnostic utility
differentiation
of mesothelioma from adenocarcinoma.
It does not differentiate mesothelioma from squamous cell carcinoma
which are usually positive. Positivity is also common in large cell
carcinomas.
differentiation
of benign (immunoreactive) from malignant (unreactive) glands in prostatic
needle biospies6, for which it may be superior
to 34bE12, although there is less experience
than with 34bE12. Both
antibodies stain the basal cells, which are deficient in adenocarcinoma.
Useful in conjunction with P504S.
|
benign |
malignant |
|
CK5/6 |
34bE12 |
CK5/6 |
34bE12 |
negative |
0/306 |
4/306 |
12/126 |
12/126 |
positive |
<50% of glands |
0/306 |
5/306 |
0/126 |
0/126 |
50-75% of glands |
1/306 |
9/306 |
0/126 |
0/126 |
75-95% of glands |
0/306 |
10/306 |
0/126 |
0/126 |
>95% of glands |
29/306 |
2/306 |
0/126 |
0/126 |
| |
CK5/6, unlike LP34, does not produce
weak staining of luminal cells and therefore it is easier to identify
acini showing two layers of cells in lobular atrophy11.
However, the staining is slightly weaker than for LP34 and intermittent
in benign acini11. Staining is strengthened by increasing
the time of antigen retrieval11.
CK5/6 may be superior for differentiation adenocarcinoma from lobular
atrophy, while LP34 may be superior in the distinction of adenocarcinoma
from PIN11.
Identification
of squamous differentiation in poorly differentiated carcinoma from
various sites, particularly when coexpressed with p6313.
References
1 Cury,
P. M.,et al. Value of the mesothelium-associated antibodies thrombomodulin,
cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural
mesothelioma from adenocarcinoma metastatic to the pleura. Mod Pathol
2000;13:107-12.
2 K
Kayser et al. Glyco- and immunohistochemical refinement of the differential
diagnosis between mesothelioma and metastatic carcinoma and survival analysis
of patients. J Pathol 2001;193:175-180.
3
Carella
R et al. Immunohistochemical panels for differentiating epithelial malignant
mesothelioma from lung adenocarcinoma. Am J Surg Pathol 2001;25:43-50.
4
Clover,
J., Oates, J., Edwards, C. Anti-cytokeratin 5/6: a positive marker for
epithelioid mesothelioma. Histopathology 1997;31:140-143.
5
Ordonez,
N. G. (1998). "Value of cytokeratin 5/6 immunostaining in distinguishing
epithelial mesothelioma of the pleura from lung adenocarcinoma."
Am J Surg Pathol 22(10): 1215-21.
6 Abrahams,
N.A., Ormsby, A.H. and Brainard, J. Validation of cytokeratin 5/6 as an
effective substitute for keratin 903 in the differentiation of benign
from malignant glands in prostate needle biopsies. Histopathology 2002;41:35-41.
7 Moll,
R., Dhouailly, D. and Sun, T.T. Expression of keratin 5 as a distinctive
feature of epithelial and biphasic mesotheliomas. An immunohistochemical
study using monoclonal antibody AE14. Virchows Arch B Cell Pathol Incl
Mol Pathol 1989;58:129-45.
8 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.
9 Abutaily,
A.S., Addis, B.J. and Roche, W.R. Immunohistochemistry in the distinction
between malignant mesothelioma and pulmonary adenocarcinoma: a critical
evaluation of new antibodies. J Clin Pathol 2002;55:662-8.
10 Miettinen,
M., J. Limon, et al. (2001). "Calretinin and other mesothelioma markers
in synovial sarcoma: analysis of antigenic similarities and differences
with malignant mesothelioma." Am J Surg Pathol 25(5): 610-7.
11 Freeman,
A., K. Treurnicht, et al. (2002). "A comparison of basal cell markers
used in the prostate." Histopathology 40(5): 492-4.
12
Jerome
Marson, V., J. Mazieres, et al. (2004). "Expression of TTF-1 and
cytokeratins in primary and secondary epithelial lung tumours: correlation
with histological type and grade." Histopathology 45(2): 125-34.
13
Kaufmann,
O., E. Fietze, et al. (2001). "Value of p63 and cytokeratin 5/6 as
immunohistochemical markers for the differential diagnosis of poorly differentiated
and undifferentiated carcinomas." Am J Clin Pathol 116(6): 823-30.
14 Reis-Filho
JS, Simpson PT, Martins A, Preto A, Gartner F,Schmitt FC Distribution
of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic
human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows
Arch 2003; 443:122-32 This study used tissue microarrays.
15 Chu
PG,Weiss LM Expression of cytokeratin 5/6 in epithelial neoplasms: an
immunohistochemical study of 509 cases. Mod Pathol 2002; 15:6-10
16
King
JE, Thatcher N, Pickering CA, et al. Sensitivity and specificity of immunohistochemical
markers used in the diagnosis of epithelioid mesothelioma: a detailed
systematic analysis using published data. Histopathology 2006; 48:223-32
17
Johansson
L Histopathologic classification of lung cancer: Relevance of cytokeratin
and TTF-1 immunophenotyping. Ann Diagn Pathol 2004; 8:259-67
This
page last revised 16.2.2006.
©SMUHT/PW
Bishop