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 Sertoli cells It inhibits the release of FSH from the pituitary gland

2. Inhibin (2) An important paracrine/autocrine regulator 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

3. 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. Anderson Cancer Center

4. Background(1) Ovarian sex cord-stromal tumors( SCSTs) 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

5. Background(2) Variable markers have been applied Inhibin: most useful to date, but not expressed by all SCSTs Calretinin WT1: found in in both ovarian surface epithelium and ovarian serous carcinoma CK, EMA, CK5/6, CD10

6. Material and method(1) Department of pathology at the university 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+

19. Discussion(1) SCSTs are morphologically heterogeneous groups D/D: ca, sa, germ cell tumor, melanoma Inhibin( a-inbibina): most useful immunomarker to date for SCSTs

20. Discussion(2) inhibin Sensitive marker, in particular for granulosa cell tumors and SLCTs Fibroma and FTs were focal or negative

21. Discussion (3) Caretinin 29 Kda calcium binding protein Neuronal tissue, mesothelial cells and ovary McCluggage and Maxwell: 36/37, Cao et al : 20/26 In our report: better than inhibin Superior in identifying the fibroma and FTs

22. Discussion(4) Caretinin The greater sensitivity of calretinin for fibromas 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

23. Discussion(5) In problematic cases, calretinin and inhibin 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

24. Discussion(6) WT1 Consistently found in ovarian surface epithelium and in ovarian serous ca In granulosa cells, a role in repressing the activity of the a inhibin promoter and thus arrest follicle development Do not correlate the calretinin and inhibin Little diagnostic utility

25. Discussion(7) CK 5/6 is consistently present in mesothelioma, 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

26. Inhibin Alpha Distinguish Hemagnioblastoma From Clear Cell Renal Cell Carcinoma ~2003 AJSP

27. Background(1) Hemangioblastoma: the endothelial and 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

28. 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 mdeulla, 1 in occipital lobe, 5 in spinal cord

29. Material and method(2) 19 RCC from 17 p ’ t A-inhibin, grade 0~3+ 10 cases from 8 p ’ t with VHL, 5 sporadic, 4 brain meta RCC NSE, EMA

34. Immunohistochemical finding(1) Inhibin A: predominantly cytoplasmic Stromal cells of all 25 hemangioblastoma expressed inhibin A No RCC expressed inhibin in this study NSE: positive in 9/9 hemangioblastoma EMA: negative in 6/6 hemagnioblastoma

40. Discussion(1) Histogenesis of the stromal cell of HAB remains unclarified due to broad immunohistochemical expression that includes vit, S-100, NSE, PR, LeuM1, Leu 7, actin, GFAP, renin and erythropoietin

41. Discussion(2) ? Modified or abnormal differentiated endothelial 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

42. 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

43. Discussion(4) The pathophysiology of inhibin expression remains 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

44. Discussion(5) Serum level of activin A and inhibin A have also 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