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

37/395, 42/437, 16/169, 6/610, 3/310, 6/611, 66/6612 , 5/613, 26/2614, 16/1616, 32/3318, 1/119, 33/3520, 28/2821, 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, 4/614, 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, 1/115, 1/121

sex cord tumour with annular tubules

2/214, 12/1221, 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, 50/508

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, 0/914, 0/1122, 0/723, 0/1224, 0/226

sertoliform endometrioid carcinoma

0/87

epithelial tumours, NOS

0/197, 0/2212, 4/5118, 3/1720, 0/1721, 0/714

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, 1/2421

ovarian small cell carcinoma

0/15, 0/77, 0/712, 0/1218, 0/1221, 0/114

extrauterine endometrial stromal sarcomas

0/57, 0/214

clear cell sarcoma

0/15

haemangiopericytoma

0/15

myxoma

0/312

carcinoid

0/518, 0/314

lymphoma

0/17, 0/212, 0/318, 0/514

struma ovarii

0/114

tumours metastatic to ovary:

 

metastatic carcinoma to ovary

0/1514

metastatic uterine clear cell carcinoma

1/38

metastatic melanoma

0/17

metastatic carcinoid to ovary

0/214

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, 3/526

thyroid carcinoma

1/426

colonic adenocarcinoma

9/1226

gallbladder adenocarcinoma

0/526

pancreatic adenocarcinoma

0/326

breast carcinoma

1/88, 4/926

lung non-small cell carcinoma

9/4829

lung adenocarcinoma

2/526, 7/3630

gastric adenocarcinoma

0/726

renal cell carcinoma

1/526

prostatic adenocarcinoma

0/726

bladder adenocarcinoma

0/226

transitional cell carcinoma

1/38

haemangiopericytoma

0/310

malignant melanoma

1/58

extra-ovarian stromal tumours

 

granular cell tumour

19/2028

gastrointestinal stromal tumours

0/3227

leiomyosarcoma

0/2827

endometrial stromal sarcoma

1/1527

uterine undifferentiated sarcoma

0/427

 

trophoblast

decidua

intrauterine products of conception

36/3625

5/40

extrauterine products of conception

4/425

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

5/525

 

uterine choriocarcinoma

2/225

 

testicular embryonal carcinoma with syncytiotrophoblastic giant cells

6/625

 

 

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

4/726

mucinous adenocarcinoma of ovary

2/526

endometrioid adenocarcinoma of ovary

1/226

endometrial adenocarcinoma

5/526

colonic adenocarcinoma

10/1226

lung adenocarcinoma

5/526

breast carcinoma

7/926

gastric adenocarcinoma

2/726

prostatic adenocarcinoma

3/726

bladder adenocarcinoma

0/226

gallbladder adenocarcinoma

1/526

renal cell carcinoma

3/526

pancreatic adenocarcinoma

2/326

thyroid carcinoma

1/426

 

 

Diagnostic utility of a-inhibin

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