Stains & CD markers

Editor-in-Chief: Debra L. Zynger, M.D.
William McDonald, M.D.

Topic Completed: 14 January 2019

Minor changes: 18 June 2021

Copyright: 2019-2021,, Inc.

PubMed Search: SF1[TI] free full text[sb]

William McDonald, M.D.
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Cite this page: McDonald W. SF1. website. Accessed October 28th, 2021.
Definition / general
  • Member of the steroid receptor superfamily; a transcription factor that regulates genes involved in gonadal and adrenal steroidogenesis
  • Present in pituitary and steroidogenic tissues:
    • Anterior pituitary gonadotrophs, which produce luteinizing hormone (LH) or follicle stimulating hormone (FSH); not found in other adenohypophyseal cell types
    • Adrenal cortex
    • Granulosa and theca cells of the ovary
    • Sertoli and Leydig cells of the testis
Essential features
  • Strong nuclear staining
  • Is expressed within the anterior pituitary gland and steroidogenic tissues of the gonads and adrenal glands
  • Within the pituitary, SF1 is the stain of choice for gonadotrophic pituitary adenomas
  • SF1 is also useful in resolving difficult differential diagnoses for tumors involving the adrenal gland and gonads
  • SF1 has roles within the pituitary and periphery; it is necessary for the development of primary steroidogenic tissue (knockout mice lack adrenal and gonadal glands)
  • In the pituitary, SF1 drives gonadotroph differentiation (J Clin Endocrinol Metab 1996;81:2165, see diagram below)
  • Gonadotroph adenomas comprise the largest category of pituitary adenomas (Arch Pathol Lab Med 2017;141:104, Mod Pathol 2018;31:900)
  • LH and FSH immunostains also mark gonadotroph adenomas but are much less sensitive (although quite specific) (Mod Pathol 2018;31:900)
  • Some labs use alpha subunit of glycoprotein hormones or estrogen receptors to supplement gonadotroph tumor workup but these lack both sensitivity and specificity (Mod Pathol 2018;31:900)
Diagrams / tables

Contributed by William McDonald, M.D.

SF1 drives gonadotroph lineage

Clinical features
  • Most gonadotroph adenomas are hormonally silent macroadenomas
  • Tumors of the adrenal cortex, ovary and testis may be difficult to distinguish from other neoplasms
  • Nuclear expression is evaluated (reactivity only in the cytoplasm is regarded as negative)
  • SF1 immunoreactivity in gonadotroph adenoma is typically diffuse, strong and nuclear (score 7 or 8 in the Allred scale, Mod Pathol 1998;11:155; see photomicrograph below)
  • SF1 immunoreactivity in anterior pituitary gland (nonneoplastic anterior pituitary) shows moderate to strong nuclear staining in scattered adenohypophysis cells; gonadotrophs are a minority population within the adenohypophysis
Uses by pathologists
Prognostic factors
  • Pituitary adenoma type is considered a prognostic factor
    • Gonadotroph adenoma is felt to be more indolent than some other types of nonfunctioning adenoma (Expert Rev Endocrinol Metab 2016;11:149)
    • Radiographic extent and adenoma classification are considered prognostic indicators
      • High risk pituitary adenomas include sparsely granulated somatotroph adenoma, lactotroph adenoma in men, Crooke cell adenoma, silent corticotroph adenoma and plurihormonal Pit1+ adenoma
    • Category of atypical adenoma was not reproducible so was removed from WHO classification (Endocrin Pathol 2017;28:228)
Microscopic (histologic) images

Contributed by William McDonald, M.D.

Normal adenohypophysis: H&E

Normal adenohypophysis: reticulin stain

Normal adenohypophysis: SF1

Adrenal cortex

Adrenal cortex

Gonadotroph adenoma: H&E

Gonadotroph adenoma: SF1

Gonadotroph adenoma: ACTH

Gonadotroph adenoma: Pit1

Positive staining - normal
Negative staining - normal
  • Corticotrophs, Pit1 family adenohypophysial cells (producing prolactin, growth hormone or TSH)
Negative staining - tumors
Board review style question #1
A 57 year old man presents with bitemporal hemianopsia, mildly elevated serum prolactin and MRI showing a 2.5 cm mass within the sella turcica, which is noted to extend upward and push on the optic chiasm. Physical examination reveals no signs of hormone excess (no evidence of gynecomastia, galactorrhea, Cushing syndrome, acromegaly, etc.) and formal visual field testing confirms decreased vision in the outer half of the visual fields. Transsphenoidal resection confirms pituitary adenoma by routine stains. The adenoma shows the following immunoreactivity: SF1+, Pit1- and ACTH-. How is this adenoma best classified?

  1. Corticotroph adenoma
  2. Gonadotroph adenoma
  3. Null cell adenoma
  4. Prolactinoma
Board review style answer #1
B. Gonadotroph adenoma. Absence of signs of hormone excess is the usual finding in gonadotroph adenoma. A small rise in prolactin can be seen in association with any lesion of the sella turcica that impinges on the stalk of the pituitary, interrupting dopaminergic inhibition of lactotrophs in the nonneoplastic anterior pituitary gland. SF1 immunohistochemistry is the most sensitive and specific means of classifying gonadotroph adenoma.

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