Inhibin
Inhibin is
a disulphide-linked dimeric 32 kDa glycoprotein hormone composed of
a and b
subunits. The
b subunit exists as at least four isoforms. Inhibin
suppresses FSH secretion. Activin, which stimulates FSH secretion, is
composed of two b
subunits. It
is therefore the presence of the a
subunit which
is specific for inhibin6.
Monoclonal
antibodies appear to have an narrower range of immunoreactivity than polyclonal
antibodies. Most published data is based on the monoclonal R1 antibody
from Serotec, which is directed against the a
subunit. E4 is directed against the bA subunit
and therefore is immunoreactive with both activin and inhibin. Antibodies
are effective on paraffin-embedded tissue6.
Immunohistochemical expression of a-inhibin
ovarian sex cord stromal tumours: |
|
granulosa
cell tumour |
37/39(30
primary adult, 5 metastatic adult, 3 primary juvenile, 1 metastatic
juvenile type)5,
42/43(31/32
adult primary, 4/4 metastatic, 7/7 juvenile)7,
16/16(13/13
adult and 3/3 juvenile)9,
6/6(ovarian
primaries)10,
3/3(metastases,
2 in the liver)10,
6/611, 66/6612 , 5/6(unilocular
cystic granulosa cell tumours)13,
26/26(24/24
adult, 2/2 juvenile)14,
16/1616, 32/3318, 1/1(metastatic
to CNS)19,
33/3520, 28/28(14/14 primary adult,
3/3 metastatic adult, 10/10 juvenile primary, 1/1 metastatic juvenile)21, 14/1422 |
Sertoli-Leydig cell tumours |
12/135, 7/87,
1/19, 10/1118,
7/1121, 8/814,
3/322 |
Sertoli cell tumour |
4/45, 17/1712,
6/1121, 1/114 |
thecoma |
8/95, 16/1812,
10/1121 |
fibrothecoma |
11/145, 4/57,
10/109, 4/6(the two negative cases
were predominantly fibromatous)14,
10/1420 |
sclerosing
stromal tumour |
2/25, 0/212,
2/214, 4/1121 |
steroid
cell |
3/35, 6/612,
2/214, 8/921 |
other
stromal neoplasms |
3/35 |
primitive
gonadal stromal tumour |
5/67, 2/314 |
gonadoblastoma |
3/314, 2/521 |
gynandroblastoma |
1/114, 1/1(positive
in adult and juvenile granulosa cell components)15,
1/121 |
sex
cord tumour with annular tubules |
2/214, 12/12(10
primary, 2 metastatic)21,
1/122 |
lipid
cell tumour |
6/77, 1/19 |
sex
cord stromal tumours, NOS |
17/1820, 1/221 |
sex cord-stromal tumours, overall |
80/875, 50/50(37/50
showed moderate to strong staining)8 |
other primary ovarian tumours: |
|
fibroma |
17/205, 0/1212,
3/1121, 2/321 |
adenofibroma |
0/95 |
fibrosarcoma |
5/85, 0/1021 |
serous
carcinoma |
1/115, 1/28,
0/726 |
atypical
mucinous neoplasm / mucinous adenocarcinoma |
0/195, 0/526 |
primary
ovarian clear cell carcinoma |
0/75, 2/28,
1/116 |
endometrioid
carcinoma |
0/155, 2/1220,
0/9(staining
only of reactive stromal cells)14,
0/11(included
six cases simulating sex cord stromal tumours)22,
0/723, 0/12(ovarian endometrioid
carcinomas with sertoliform features: luteinised stromal cells
positive in 10 cases)24,
0/226 |
sertoliform
endometrioid carcinoma |
0/87 |
epithelial
tumours, NOS |
0/19(the
epithelial component is negative; there may be positivity in luteinised
stromal cells)7,
0/2212, 4/5118, 3/17(poorly
differentiated primary and metastatic)20,
0/1721, 0/7(poorly differentiated
primary tumours: staining only of reactive stromal cells)14 |
Brenner
tumour |
0/135, 1/920 |
Wolffian adnexal tumour |
9/1021 |
malignant
mixed Müllerian tumour |
0/25, 0/1212 |
dysgerminoma |
0/75, 0/618 |
yolk
sac tumour |
0/55 |
choriocarcinoma |
0/15 |
embryonal
carcinoma |
0/15 |
immature
teratoma |
0/45 |
mixed
germ cell tumour |
0/45, 0/612,
1/24(positivity
in one case in a focus of syncytiotrophoblast)21 |
ovarian
small cell carcinoma |
0/15, 0/7(hypercalcaemic
type)7, 0/712, 0/1218,
0/12(hypercalcaemic
type)21, 0/1(hypercalcaemic
type)14 |
extrauterine
endometrial stromal sarcomas |
0/57, 0/214 |
clear
cell sarcoma |
0/15 |
haemangiopericytoma |
0/15 |
myxoma |
0/312 |
carcinoid |
0/518, 0/3(staining
only of reactive stromal cells)14 |
lymphoma |
0/17, 0/212,
0/318, 0/514 |
struma
ovarii |
0/114 |
tumours metastatic to ovary: |
|
metastatic
carcinoma to ovary |
0/15(GI
x 5, breast x 2, lung x 1, unknown x7, including two of Krukenberg
type: staining only of reactive stromal cells)14 |
metastatic
uterine clear cell carcinoma |
1/38 |
metastatic
melanoma |
0/17 |
metastatic
carcinoid to ovary |
0/2(from
gastrointestinal tract)14 |
endometrial
stromal sarcoma metastatic from uterus |
0/214 |
testicular tumours: |
|
Leydig
cell tumour |
15/1617 |
testicular
sex cord-stromal tumors with varying degrees of Sertoli or granulosa
cell differentiation |
4/617 |
sex
cord-stromal tumors, NOS |
2/317 |
extra-ovarian tumours: |
|
uterine
endometrioid carcinoma |
1/28, 3/5(weak)26 |
thyroid
carcinoma |
1/4(strong)26 |
colonic
adenocarcinoma |
9/12(1
strong, 8 weak)26 |
gallbladder
adenocarcinoma |
0/526 |
pancreatic
adenocarcinoma |
0/326 |
breast
carcinoma |
1/88, 4/9(1
strong, 3 weak)26 |
lung
non-small cell carcinoma |
9/4829 |
lung
adenocarcinoma |
2/5(1
strong, 1 weak)26,
7/3630 |
gastric
adenocarcinoma |
0/726 |
renal
cell carcinoma |
1/5(strong)26 |
prostatic
adenocarcinoma |
0/726 |
bladder
adenocarcinoma |
0/226 |
transitional
cell carcinoma |
1/38 |
haemangiopericytoma |
0/3(in
males)10 |
malignant
melanoma |
1/58 |
extra-ovarian stromal tumours |
|
granular cell tumour |
19/2028 |
gastrointestinal stromal
tumours |
0/3227 |
leiomyosarcoma |
0/28(20
uterine, 2 colon, 2 skin, 2 retroperitoneal, 1 urinary bladder)27 |
endometrial stromal sarcoma |
1/15(weak
positivity only in one case in sex-cord like areas)27 |
uterine
undifferentiated sarcoma |
0/427 |
| |
trophoblast |
decidua |
intrauterine
products of conception |
36/36(villous
trophoblast and extravillous trophoblastic giant cells and some
extravillous mononuclear trophoblastic cells)25 |
5/40 |
extrauterine
products of conception |
4/4(villous
trophoblast and extravillous trophoblastic giant cells and some
extravillous mononuclear trophoblastic cells)25 |
1/425 |
decidualised
endometrium in context of ectopic gestation |
|
2/725 |
decidualised
endometrium in context of progesterone therapy |
|
2/825 |
Extrauterine
decidualised tissue in context of intrauterine pregnancy |
|
1/325 |
hydatidiform
mole |
5/5(villous
trophoblast)25 |
|
uterine
choriocarcinoma |
2/2(strong
staining of scattered cells, both mononuclear and multinucleate)25 |
|
testicular
embryonal carcinoma with syncytiotrophoblastic giant cells |
6/6(syncytiotrophoblastic
giant cells)25 |
|
| |
Inhibin immunoreactivity has been reported in hepatocellular
carcinoma and as possibly useful in the differentiation of hepatocellular
carcinomas (positive) from adenocarcinomas (negative)1.
However, a subsequent publication indicates that the reported immunopositivity
of HCC and non-tumoral hepatocytes for inhibin represents a false-positive
result due to endogenous biotin2.
Immunohistochemical expression of b-inhibin (activin)
Activin
is expressed by ovarian epithelial tumours and is demonstrated by antibody
E4. Relatively little has been published, but it does not appear to be
specific for ovarian carcinomas26:
| |
|
|
serous
adenocarcinoma of ovary |
4/7(weak)26 |
mucinous
adenocarcinoma of ovary |
2/5(weak)26 |
endometrioid
adenocarcinoma of ovary |
1/2(weak)26 |
endometrial
adenocarcinoma |
5/5(weak)26 |
colonic
adenocarcinoma |
10/12(1
strong, 9 weak)26 |
lung adenocarcinoma |
5/5(1
strong, 4 weak)26 |
breast
carcinoma |
7/9(weak)26 |
gastric
adenocarcinoma |
2/7(weak)26 |
prostatic
adenocarcinoma |
3/7(weak)26 |
bladder
adenocarcinoma |
0/226 |
gallbladder
adenocarcinoma |
1/5(weak)26 |
renal
cell carcinoma |
3/5(weak)26 |
pancreatic
adenocarcinoma |
2/3(weak)26 |
thyroid
carcinoma |
1/4(weak)26 |
| |
Diagnostic utility of a-inhibin
Identification of ovarian granulosa cell tumours and
Sertoli cell tumours:
Differentiation of sex cord stromal tumours from reactive
mesothlium in peritoneal washings, a situation in which calretinin
is unhelpful6.
Possibly in the identification of choriocarcinoma25
Possibly in the identification of syncytiotrophoblast
in testicular tumours25
References
1McCluggage
WG. Maxwell P. Patterson A. Sloan JM. Immunohistochemical staining of
hepatocellular carcinoma with monoclonal antibody against inhibin. Histopathology
1997;30(6):518-22.
2Iezzoni
JC. Mills SE. Pelkey TJ. Stoler MH. Inhibin is not an immunohistochemical
marker for hepatocellular carcinoma. An example of the potential pitfall
in diagnostic immunohistochemistry caused by endogenous biotin.Am J Clin
Pathol 1999;111(2):229-34.
3McCluggage,
W. G. Uterine tumours resembling ovarian sex cord tumours: immunohistochemical
evidence for true sex cord differentiation. Histopathology 1999;34:375-6.
4Krishnamurthy,
S., Jungbluth, A. A., Busam, K. J., Rosai, J. Uterine tumors resembling
ovarian sex-cord tumors have an immunophenotype consistent with true sex-cord
differentiation. Am J Surg Pathol 1998;22:1078-1082.
5Movahedi-Lankarani,
S. and Kurman, R.J. Calretinin, a more sensitive but less specific marker
than alpha- inhibin for ovarian sex cord-stromal neoplasms: an immunohistochemical
study of 215 cases. Am J Surg Pathol 2002;26:1477-83.
6Zheng,
W., Senturk, B.Z. and Parkash, V. Inhibin immunohistochemical staining:
a practical approach for the surgical pathologist in the diagnoses of
ovarian sex cord-stromal tumors. Adv Anat Pathol 2003;10:27-38.
7Rishi,
M., Howard, L.N., Bratthauer, G.L. and Tavassoli, F.A. Use of monoclonal
antibody against human inhibin as a marker for sex cord-stromal tumors
of the ovary. Am J Surg Pathol 1997;21:583-9.
8Pelkey,
T.J., Frierson, H.F., Jr., Mills, S.E. and Stoler, M.H. The diagnostic
utility of inhibin staining in ovarian neoplasms. Int J Gynecol Pathol
1998;17:97-105.
9Flemming,
P., Grothe, W., Maschek, H., Petry, K.U., Wellmann, A. and Georgii, A.
The site of inhibin production in ovarian neoplasms. Histopathology 1996;29:465-8.
10Flemming,
P., Wellmann, A., Maschek, H., Lang, H. and Georgii, A. Monoclonal antibodies
against inhibin represent key markers of adult granulosa cell tumors of
the ovary even in their metastases. A report of three cases with late
metastasis, being previously misinterpreted as hemangiopericytoma. Am
J Surg Pathol 1995;19:927-33.
11Arora,
D.S., Cooke, I.E., Ganesan, T.S., Ramsdale, J., Manek, S., Charnock, F.M.,
Groome, N.P. and Wells, M. Immunohistochemical expression of inhibin/activin
subunits in epithelial and granulosa cell tumours of the ovary. J Pathol
1997;181:413-8.
12Costa,
M.J., Ames, P.F., Walls, J. and Roth, L.M. Inhibin immunohistochemistry
applied to ovarian neoplasms: a novel, effective, diagnostic tool. Hum
Pathol 1997;28:1247-54.
13Mulvany,
N.J. and Riley, C.B. Granulosa cell tumors of unilocular cystic type.
Pathology 1997;29:348-53.
14Stewart,
C.J., Jeffers, M.D. and Kennedy, A. Diagnostic value of inhibin immunoreactivity
in ovarian gonadal stromal tumours and their histological mimics. Histopathology
1997;31:67-74.
15McCluggage,
W.G., Sloan, J.M., Murnaghan, M. and White, R. Gynandroblastoma of ovary
with juvenile granulosa cell component and heterologous intestinal type
glands. Histopathology 1996;29:253-7.
16McCluggage,
W.G., Maxwell, P. and Sloan, J.M. Immunohistochemical staining of ovarian
granulosa cell tumors with monoclonal antibody against inhibin. Hum Pathol
1997;28:1034-8.
17McCluggage,
W.G., Shanks, J.H., Whiteside, C., Maxwell, P., Banerjee, S.S. and Biggart,
J.D. Immunohistochemical study of testicular sex cord-stromal tumors,
including staining with anti-inhibin antibody. Am J Surg Pathol 1998;22:615-9.
18Riopel,
M.A., Perlman, E.J., Seidman, J.D., Kurman, R.J. and Sherman, M.E. Inhibin
and epithelial membrane antigen immunohistochemistry assist in the diagnosis
of sex cord-stromal tumors and provide clues to the histogenesis of hypercalcemic
small cell carcinomas. Int J Gynecol Pathol 1998;17:46-53.
19Schnittger,
C., Soudah, B., von Wasielewski, R., de Groot, M., Haubitz, B., Becker,
H. and Dengler, R. Infiltration of the central nervous system by a granulosa
cell tumor immunostained by antibodies against inhibin. Neurology 1998;50:560-2.
20Hildebrandt,
R.H., Rouse, R.V. and Longacre, T.A. Value of inhibin in the identification
of granulosa cell tumors of the ovary. Hum Pathol 1997;28:1387-95.
21Kommoss,
F., Oliva, E., Bhan, A.K., Young, R.H. and Scully, R.E. Inhibin expression
in ovarian tumors and tumor-like lesions: an immunohistochemical study.
Mod Pathol 1998;11:656-64.
22Guerrieri,
C., Franlund, B., Malmstrom, H. and Boeryd, B. Ovarian endometrioid carcinomas
simulating sex cord-stromal tumors: a study using inhibin and cytokeratin
7. Int J Gynecol Pathol 1998;17:266-71.
23Matias-Guiu,
X., Pons, C. and Prat, J. Mullerian inhibiting substance, alpha-inhibin,
and CD99 expression in sex cord-stromal tumors and endometrioid ovarian
carcinomas resembling sex cord-stromal tumors. Hum Pathol 1998;29:840-5.
24Ordi,
J., Schammel, D.P., Rasekh, L. and Tavassoli, F.A. Sertoliform endometrioid
carcinomas of the ovary: a clinicopathologic and immunohistochemical study
of 13 cases. Mod Pathol 1999;12:933-40.
25McCluggage,
W.G., Ashe, P., McBride, H., Maxwell, P. and Sloan, J.M. Localization
of the cellular expression of inhibin in trophoblastic tissue. Histopathology
1998;32:252-6.
26McCluggage,
W.G. and Maxwell, P. Adenocarcinomas of various sites may exhibit immunoreactivity
with anti- inhibin antibodies. Histopathology 1999;35:216-20.
27Shah,
V.I., Freites, O.N., Maxwell, P. and McCluggage, W.G. Inhibin is more
specific than calretinin as an immunohistochemical marker for differentiating
sarcomatoid granulosa cell tumour of the ovary from other spindle cell
neoplasms. J Clin Pathol 2003;56:221-4.
28Zamecnik,
M., Michal, M. and Mukensnabl, P. Reactivity of granular cell tumors for
inhibin and other markers of sex cord and steroid cell differentiation.
Am J Surg Pathol 2003;27:413-4.
29 Tigrani DY WJ. Expression of inhibin-alpha
in primary pulmonary non-small cell carcinoma by immunohisochemistry.
Modern Pathology. 2008;21:352A.
30 Zhang K SJ, Lin, F. Expression of
Inhibin-alpha in Non-Small Cell Carcinoma of the Lung with a Focus on
Adenocarcinoma – A Diagnostic Pitfall in the Evaluation of Metastatic
Pulmonary Carcinoma. Modern Pathology. 2008;21:353A.
This page last
revised 28.11.2010.
©SMUHT/PW
Bishop