Immunohistochemistry of lung carcinomas
for cytokeratins and neuroendocrine markers
Cytokeratins:
|
|
AE1 |
AE3 |
BG-8 |
Cam5.2 |
35BH11
(LMW CK) |
34bE1234b2(HMW
CK) |
B72.3 |
small cell carcinoma |
5 |
6/65 |
11/115 |
4/65 |
5/65,
13/1330 |
19/3515 |
12% (, 3/43(variously bronchial
biopsies, FNAs or bronchial washings)14,
9/35(some
cases counted as positive showed reactivity of 1-10% of cells)15,
7/56(the
positive foci were composed of larger cells and suggested minimal
squamous or glandular differentiation.)13,
0/1016
|
2/375 |
carcinoid |
|
|
|
|
|
|
0/50(27
typical and 23 atypical. Entrapped bronchial epithelium is intensely
positive)13,
0/10(5
typical and 5 atypical)14 |
|
large
cell carcinoma (non-endocrine) |
9/95 |
|
|
|
9/930 |
|
8/95 |
4/95 |
large
cell neuroendocrine |
6/65 |
|
|
|
|
|
1/6(One case showed positivity
but in less than 10% of cells.), 1/44(One case showed scattered
weakly positive cells.),
11/64(in
all cases, <10% of cells stained)13,
0/214,
0/332 |
3/65 |
adenocarcinoma |
33/335 |
8/85 |
8/85 |
7/85 |
8/85,
11/1130 |
|
14/335,
8/2610, 10/10(variously bronchial
biopsies, FNAs or bronchial washings: poorly differentiated)14,
0/1432 |
29/335 |
bronchioloalveolar
see also mucinous bronchioloalveolar |
13/135 |
3/35 |
3/35 |
2/35 |
3/35 |
|
12/135 |
|
adenosquamous carcinoma |
|
|
|
|
|
|
1/132 |
|
basaloid
carcinoma |
|
|
|
|
|
|
5/514 |
|
squamous cell carcinoma |
37/375 |
12/125 |
12/125 |
10/125 |
12/125,
12/1230 |
|
98%(41/425,
28/28(basaloid
variant of squamous cell carcinoma)10,
15/16(variously
bronchial biopsies, FNAs or bronchial washings: poorly differentiated.
Staining was focal - less than 5% of tumour cells)14,
22/23(basaloid
squamous cell carcinomas)16,
5/532 ) |
31/375 |
| |
CK5/6 |
CK7 |
CK14 |
CK17 |
CK19 |
CK20 |
small
cell carcinoma |
0%21,
1/30(positivity
only in a squamous component)22,
2/2831 |
2/385, 2/117, 11%21,
11/30(dot-like)22, 11/1330
|
2/375, 1/76, 5%21
|
2/385 |
80%21,
23/30(dot-like)22
|
0/115, 0/117, 1%21,0/3022, 2/1330
|
carcinoid |
10%21,
0/2322
|
2/912,
10/1611, 21%21,1/2322 |
0/96 |
|
20%21,16/2322 |
0/912,
0/1611, 0%21,0/2322 |
large cell carcinoma
(non-endocrine) |
0/2522 |
5/95,10/2522, 8/930 |
6/95 |
6/95 |
9/2522 |
0/617,0/2522,
0/930
|
large
cell neuroendocrine |
17%21,
3/1022
|
2/65, 33%21,7/1022, 2/332
|
1/65, 17%21
|
0/65 |
0%21,
8/10(dot-line
in some cases)22
|
1/1022 |
adenocarcinoma |
0/3022 ,
2/1031, 3/66(using cell blocks
from FNA samples, correlated with subsequent surgical specimens.)35
|
31/335,
45/547, 70/748, 80/8020,
30/3022, 11/1130, 15/1532,
66/66(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.)35 |
7/335,
2/106 |
5/335 |
30/3022,8/1022, 30/3022 |
0/85,
6/547, 6/748,
6/699, 13/212(5 cases with <25%
of cells positive, 3 cases with 26-50% of cells positive, 2 cases
with 51-75% of cells positive, 3 cases with >75% of cells positive.
Positive cases were 6 mixed, 4 acinar and 3 papillary.)17, 10/80(
positivity focal in six cases, 10-25% of cells in one case, 26-75%
in one case and >75% in two cases)20,1/3022, 1/1130 |
bronchioloalveolar
see also mucinous
bronchioloalveolar |
0/1422 |
13/135,
3/37 , 26/26(positivity in 51-75%
of tumour in one case, >75% in 25 cases)18,
14/1420,13/1422 |
5/135 |
1/135 |
14/1422 |
0/35,
0/37, 1/26(positivity in 26-50%
of tumour in one case)18,
4/14(
positivity 10-25% of cells in one case, 26-75% in one case and
>75% in two cases20,0/1422 |
adenosquamous
carcinoma |
squamous
component 3/3, glandular component 1/322,
1/1(using cell blocks from FNA samples, correlated
with subsequent surgical specimens.)
35
|
squamous
component 0/3, glandular component 2/322,
1/1(using cell blocks from FNA samples, correlated
with subsequent surgical specimens.)
35 |
|
|
3/3(both components positive) |
0/322 |
squamous
cell carcinoma |
30/30(predominantly intense
diffuse and membrane staining: less strong in poorly differentiated
tumours.)22,
31/3931, 19/24(using cell blocks
from FNA samples, correlated with subsequent surgical specimens.)
35 |
8/375,
0/127, 7/30(positivity often seen
in areas without either squamous or glandular differentiation)22, 4/1230,
0/532, 15/24(using cell blocks
from FNA samples, correlated with subsequent surgical specimens.)
35 |
35/375,
13/156 |
34/375 |
30/3022
|
0/125,
1/127, 0/4117,
1/30(positivity
of 5% of cells in one case)22,
1/1230
|
In combined large cell neuroendocrine carcinomas, only the squamous
component (6/613)
or adenocarcinomatous component (5/613)
shows positivity for 34betaE12: combined small cell / squamous cell carcinomas
show positivity of the squamous cell component (3/313),
but combined small cell / large cell neuroendocrine carcinomas show no
positivity (0/513).
Neuroendocrine markers:
Neuroendocrine differentiation occurs in non small cell carcinomas.
Reports have been conflicting as to clinical or prognostic significance26.
|
CD
56 |
chromogranin |
synaptophysin |
small
cell carcinoma |
64/662,
8/1014 |
37% (7/662,
32/385, 8/181, 19/43(with
microwave treatment: 4/43 without microwave treatment)14, 8/3515) |
54%
(27/662, 21/365, 9/1014,
23/3515) |
carcinoid |
9/11(nine
cases showed tumour cell membrane staining: the remaining two
showed staining of sustentacular cells)3,
7/1014 |
15/17(foregut
carcinoids: 11 lung, 4 gastric and 2 duodenal)3,
10/10(5
typical and 5 atypical)14 |
11/113,
8/10(4/5
typical and 4/5 atypical)14 |
large cell carcinoma
(non-neuroendocrine) |
2/32,
2/3526 |
0/32,
1/95, 0/3526 |
0/32,
1/95, 3/3526 |
large
cell neuroendocrine |
2/22,
40/4410, 2/214, 4/432 |
0/22,
30/4410, 5/65, 2/2(with
microwave treatment)14 |
2/22,
37/4410, 6/65, 2/2(focal
- less than 5% of tumour cells)14 |
adenocarcinoma |
1/382,
0/254, 1/10(poorly differentiated)14, 11/209(2
of the positive cases were also positive for synaptophysin, none
for chromogranin)26, 0/1432 |
0/382,
3/671, 2/335,
0/10(poorly
differentiated)14,
1/209(the
one positive case was also positive for synaptophysin)26 |
1/382,
2/335, 0/10(poorly differentiated)14, 23/20926 |
bronchioloalveolar |
|
0/135 |
0/135 |
basaloid
carcinoma |
3/2810,
1/5(focal
- less than 5% of cells)14 |
0/2810,
1/514
|
1/2810,
1/514 |
squamous
cell carcinoma |
4/522,
0/254, 2/16(poorly differentiated)14, 29/242(2
cases were positive for both CD56 and synaptophysin, one for CD56
and chromogranin, none for all three)26, 0/532 |
1/522,
2/375, 0/16(poorly differentiated)14, 1/242(the
one positive case was also positive for CD56, not for synaptophysin)26 |
1/522,
0/355, 0/16(poorly differentiated)14, 10/24226 |
Other neuroendocrine markers in small
cell carcinoma: bombesin; 28/3515, neurofilament;
24/3515,
NSE; 21/3515,
ACTH; 0/3515
There is preliminary evidence the desmocollin-3 may be useful in the
identification of squamous cell differentiation33.
Diagnostic utility
Various panels of antibodies have been
recommended29.
Differentiation
of non-small cell carcinoma from small cell carcinoma5. 34bE123, CK5/6,
CK14 and CK17
all preferentially stain squamous cell carcinomas. If the threshold is
set at 10% of cells showing Immunoreactivity, 34bE12 excludes
all neuroendocrine tumours. CK7 and B72.3 stain adenocarcinomas, where they
have a complementary role; those adenocarcinomas staining weakly with
one tend to stain strongly with the other. Conversely, small cell carcinomas
are usually positive for CD 56, chromogranin
and synaptophysin.
Differentiating
the intermediate type of small cell carcinoma from poorly differentiated
squamous cell carcinoma ("small
cell variant") may be particularly difficult. Small cell carcinoma
is more likely to be positive for CD56 and to
show punctate positivity for Cam5.2.
Non-small cell carcinoma is more likely to be positive for 34bE12
and CK5/6.
Cytokeratin 14 should be positive in
squamous cell carcinoma, but my personal experience is that in poorly
differentiated squamous cell carcinoma it is often negative. p63 and
TTF-1 both
have the advantage of being nuclear stains, avoiding the problem of scant
cytoplasm in small cell carcinoma and in the small cell variant of squamous
cell carcinoma: they have been applied in a panel to previously 24.
|
p16 |
p63 |
p40 |
Desmocollin-3 |
TTF-1 |
Napsin |
34bE12 |
|
small
cell carcinoma |
28/28(high
level of staining in 27 cases, low level in one case)23 |
0/23(17
tissue and 6 cytology)19,
0/2823,
0/13(this
study was performed using a panel of p63 and TTF-1 on previously
Papanicolaou - stained cytological smears and cytospin preparations)24,
negative(using
destained cytological material)27,
0/16(using
cell block cytological material)28 ,
0/2831
|
|
|
20/23(17
tissue and 6 cytology)19,
26/2823,
12/13(this
study was performed using a panel of p63 and TTF-1 on previously
Papanicolaou - stained cytological smears and cytospin preparations)24,
28/2831 |
|
0/2823 |
|
squamous
cell carcinoma |
15/28(includes
seven cases with a component of small call variant of squamous
carcinoma, which had the same profile as the conventional poorly
differentiated squamous cell carcinoma)23 |
13/13(12
tissue and 1 cytology)19,
28/28(includes
seven cases with a component of small call variant of squamous
carcinoma, which had the same profile as the conventional poorly
differentiated squamous cell carcinoma)23,
13/13(this
study was performed using a panel of p63 and TTF-1 on previously
Papanicolaou - stained cytological smears and cytospin preparations)24, positive(using
destained cytological material)27,
4/4(using
cell block cytological material)28 ,
32/3931, 24/24Type your expanding
text here.35 |
15/15(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
20/2034,
4/4(cytological
specimens with the line of differentiation subsequently determined
by biopsy or excision specimens)34,
13/15(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
0/13(12
tissue and 1 cytology)19,
1/28(includes
seven cases with a component of small call variant of squamous
carcinoma, which had the same profile as the conventional poorly
differentiated squamous cell carcinoma)23,
0/13(this
study was performed using a panel of p63 and TTF-1 on previously
Papanicolaou - stained cytological smears and cytospin preparations),
2/2034, 0/4(cytological specimens
with the line of differentiation subsequently determined by biopsy
or excision specimens)34,
0/24(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35
7%; see
TTF-1, lung, squamous cell carcinoma |
0/1535 |
28/28(includes seven cases
with a component of small call variant of squamous carcinoma,
which had the same profile as the conventional poorly differentiated
squamous cell carcinoma)23 |
|
primary adenocarcinoma |
|
0/12(using
destained cytological material)27,
0/4(using
cell block cytological material)28 ,
0/1031, 13/66(using cell blocks
from FNA samples, correlated with subsequent surgical specimens.)
35 |
1/29(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
1/2034, 0/20(cytological
specimens with the line of differentiation subsequently determined
by biopsy or excision specimens)34,
0/29(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
18/2034, 7/20(cytological
specimens with the line of differentiation subsequently determined
by biopsy or excision specimens in which 16/20 were positive)34,
78%; see
TTF-1, lung, adenocarcinoma |
11/29(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
|
|
adenocarcinoma metastatic to lung |
|
0/5(using
destained cytological material)27,
0/6(using
cell block cytological material)28
|
|
|
|
|
|
|
adenosquamous carcinoma |
|
1/1235,
1/1(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
1/1(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
3/334,
0/1(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
3/334, 0/1(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
0/1(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
|
|
large cell carcinoma |
|
0/4(using
destained cytological material)27
|
|
27/4934,
1/7 (cytological
specimens with the line of differentiation subsequently determined
by biopsy or excision specimens in which 2/7 were positive) 34, 2/12(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
24/49(staining
for Desmocollin-3 and TTF-1 were mutually exclusive)34, 1/7(cytological
specimens with the line of differentiation subsequently determined
by biopsy or excision specimens in which 5/7 were positive)34 |
|
|
|
| sarcomatoid
carcinoma |
|
|
|
0/334 |
0/334 |
|
|
|
| large
cell / sarcomatoid carcinoma |
|
7/12(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
3/12(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
2/12(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
3/12(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
1/12(using
cell blocks from FNA samples, correlated with subsequent surgical
specimens.) 35 |
|
|
While immunoreactivity for 34bE12
increases with the degree of keratinisation, staining for p63 shows an
inverse relation to keratinisation and is therefore particularly useful
in poorly differentiated squamous cell carcinomas23.
p16 may be positive in TTF-1-negative small cell carcinomas23.
Large cell neuroendocrine carcinomas
are often positive for CK7, while carcinoid
tumours are almost invariably
negative.
Small cell carcinomas tend to show greater staining with CD56 than with
synaptophysin or chromogranin, whereas the converse holds for carcinoid
tumours25.
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page last revised 20.7.201.