Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family,...

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Inhibin, dimetric 32-kDa peptide h ormone that belongs to the transfor ming growth factor beta family, it is produced by ovarian granulosa ce lls and testicular Sertoli cells It inhibits the release of FSH from the pituitary gland
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Transcript of Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family,...

Page 1: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular Sertoli cells

It inhibits the release of FSH from the pituitary gland

Page 2: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Inhibin (2) An important paracrine/autocrine regul

ator of differentiation and proliferation of various tissue

inhibin mRNA:ovary, testis, placenta, pituitary gland, adrenal cortex, BM, kidney, spinal cord, pancreas

IHC: Leydig, granulosa, thecal and pituitary somatotrophs

Page 3: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Ovarian Sex Cord-Stromal Tumor: An Immunohistochemical study Including a Comparison Of Calretinin and Inhibin

~ 2003 Modern pathology department of Pathology, the university of Texas M.D. A

nderson Cancer Center

Page 4: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Background(1) Ovarian sex cord-stromal tumors( SCST

s) account for about 8% of ovarian tumors

Composed of cells derived from gonadal sex cords, specialized gonadal stroma and fibroblasts

Morphology range from entirely glandular to entirely spindled

Page 5: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Background(2) Variable markers have been applied Inhibin: most useful to date, but not exp

ressed by all SCSTs Calretinin WT1: found in in both ovarian surface e

pithelium and ovarian serous carcinoma

CK, EMA, CK5/6, CD10

Page 6: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Material and method(1) Department of pathology at the univers

ity of Texas M.D. Anderson cancer center

53 SCSTs: 17 AGCTs, 4 JGCTs, 3 SCTATs, 9 SLCTs, 10 fibromas, 5 fibrothecoma and 5 thecomas

8 cases were from metastatic sites Grade:0~4+

Page 7: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 8: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 9: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 10: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 11: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 12: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 13: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 14: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 15: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 16: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 17: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 18: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 19: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(1) SCSTs are morphologically heterogene

ous groups D/D: ca, sa, germ cell tumor, melanoma Inhibin( a-inbibina): most useful immun

omarker to date for SCSTs

Page 20: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(2) inhibin Sensitive marker, in particular for granul

osa cell tumors and SLCTs Fibroma and FTs were focal or negative

Page 21: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion (3) Caretinin 29 Kda calcium binding protein Neuronal tissue, mesothelial cells and o

vary McCluggage and Maxwell: 36/37, Cao et

al : 20/26 In our report: better than inhibin Superior in identifying the fibroma and

FTs

Page 22: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(4) Caretinin The greater sensitivity of calretinin for fibrom

as and FTs could be useful in cases in which the differential diagnosis includes ESS with a fibroma-like appearance

The combination of calretinin and CD10 may be useful in helping to distinguish

The two markers also could play a complementary role in meta SCSTs

Page 23: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(5) In problematic cases, calretinin and inhi

bin are best used part of a large of antibodies

Keratin can be found in both CA and SCSTs, EMA may be useful distinguish between the two entities

Page 24: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(6) WT1 Consistently found in ovarian surface epitheli

um and in ovarian serous ca In granulosa cells, a role in repressing the acti

vity of the a inhibin promoter and thus arrest follicle development

Do not correlate the calretinin and inhibin Little diagnostic utility

Page 25: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(7) CK 5/6 is consistently present in mesoth

elioma, it was not found in any of the SCSTs tested

Calretinin comprares favorably to inhibin as a marker of SCSTs, at least as sensitive as inhibin in most categories and more sensitive for fibromas and FTs

Page 26: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Inhibin Alpha Distinguish Hemagnioblastoma From Clear Cell Renal Cell Carcinoma

~2003 AJSP

Page 27: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Background(1) Hemangioblastoma: the endothelial an

d pericytic components are vascular, the origin of the stromal elements has not been elucidated

Cerebellum, spinal cord Distinguish hemgioblastoma from meta

RCC continues to be a diagnostic challenge

Page 28: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Material and method(1) 1990~2002 university of Texas Southwestern

Medical Center and Veterans Affairs Medical Center, Dallas, Texas

25 hemangioblastoma from 22 p’t, 11 cases from 8 p’t with VHL dx 18 in the cerebellum/posterior fossa, 1 in mde

ulla, 1 in occipital lobe, 5 in spinal cord

Page 29: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Material and method(2) 19 RCC from 17 p’t A-inhibin, grade 0~3+ 10 cases from 8 p’t with VHL, 5 sporadi

c, 4 brain meta RCC NSE, EMA

Page 30: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 31: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 32: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 33: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 34: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Immunohistochemical finding(1) Inhibin A: predominantly cytoplasmic Stromal cells of all 25 hemangioblastoma exp

ressed inhibin A No RCC expressed inhibin in this study NSE: positive in 9/9 hemangioblastoma EMA: negative in 6/6 hemagnioblastoma

Page 35: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 36: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 37: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 38: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 39: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.
Page 40: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(1) Histogenesis of the stromal cell of HAB r

emains unclarified due to broad immunohistochemical expression that includes vit, S-100, NSE, PR, LeuM1, Leu 7, actin, GFAP, renin and erythropoietin

Page 41: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(2) ? Modified or abnormal differentiated e

ndothelial cells and pericytes or neuroendocrine feature or originate form embryonal plexus epi or histiocytic origin

Since p’t with WHL are predioposed to develop both HAB and RCC, distinguish the two tumors is of clinical importance

Page 42: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(3) NSE, EMA, CAM5.2 Inhibin seems to be a helpful marker in

distinguish HAB and RCC, similar to previous study

In our study, no difference in the inhibin A staining pattern between sporadic and VHL associated HAB

Page 43: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(4) The pathophysiology of inhibin expression re

mains unknown One possibility: endodermally derived epi and

primitive mesenchyme Serum inhibin level has been used as an early

marker of tumor growth and recurrent dx in p’t with granulosa cell tumor

Page 44: Inhibin, dimetric 32-kDa peptide hormone that belongs to the transforming growth factor beta family, it is produced by ovarian granulosa cells and testicular.

Discussion(5) Serum level of activin A and inhibin A have als

o recently been described as potential markers for hydatidiform mole

The consistent expression of inhibin A by HAB raise the potential diagnostic value of serum inhibin A in monitoring either tumor development or recurrence in the VHL