GCDFP-15

Synonyms: Gross Cystic Disease Fluid Protein-15

by Jan Klos

Background

Gross Cystic Disease Fluid Protein-15 (GCDFP-15) is a 15 kDa prolactin induced protein, encoded at chromosome 7q34 encoded by the PIP gene. Its physiological function is a regulation of water transport in secretory cells. The level of expression is upregulated by prolactin and androgens and downregulated by estrogen.

Positive staining in normal cells

Secretory cells of mammary gland, apocrine and eccrine sweat glands, lacrimal, ceruminous, serous salivary and bronchial glands. Secretory cells in prostate and seminal vesicles are also found positive.

Positive staining in tumors

20-80% of breast carcinomas is positive depending on type and differentiation grade of the tumor (the level of expression is significantly lower in poorly differentiated carcinomas, while well differentiated carcinomas especially these with apocrine differentiation and lobular carcinomas show quite high percentage of positive staining).  Percentage of positive staining in breast carcinomas is lower in metastatic setting. Around 40-50% of mammary Paget`s disease and around 70% of extramammary Paget`s disease are positive. Many tumors of salivary, sweat glands or lacrimal glands stain positive.  Varying percentage (10-30%) of carcinomas originating from the ovary and pancreas are reported positive. Only few carcinomas in other organs are found to express this protein (i.e. 5 % lung adenocarcinoma are reported positive for GCDFP-15 and often co-expressing TTF1)

Staining pattern

Staining pattern is cytoplasmic and diffuse often with accentuation of luminal apocrine secretion. In metastatic setting only single, scattered cells may be stained.

Application

  • GCDFP15 is a quite specific, but not particularly sensitive marker of origin of carcinoma (positive staining supports origin in mammary, sweat, lacrimal or salivary gland).
  • Recommended to use in panel.

Selected references

  1. Bhargava R, Beriwal S, Dabbs DJ. Mammaglobin vs GCDFP-15: an immunohistologic validation survey for sensitivity and specificity. Am J Clin Pathol. 2007 Jan;127(1):103-13.
  2. Fritzsche FR, Thomas A, Winzer KJ, et al. Co-expression and prognostic value of gross cystic disease fluid protein 15 and mammaglobin in primary breast cancer. Histol Histopathol. 2007 Nov;22(11):1221-30.
  3. https://app.immunoquery.com/engine/abpanel?abs=GCDFP-15
  4. https://en.wikipedia.org/wiki/Prolactin-induced_protein
  5. Liegl B, Leibl S, Gogg-Kamerer M, et al. Mammary and extramammary Paget’s disease: an immunohistochemical study of 83 cases. Histopathology. 2007 Mar;50(4):439-47.
  6. Middleton LP, Palacios DM, Bryant BR, et al. Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis. Am J Surg Pathol. 2000 Dec;24(12):1650-6.
  7. Moritani S, Ichihara S, Hasegawa M, et al. Serous papillary adenocarcinoma of the female genital organs and invasive micropapillary carcinoma of the breast. Are WT1, CA125, and GCDFP-15 useful in differential diagnosis? Hum Pathol. 2008 May;39(5):666-71. Epub 2008 Mar 12.
  8. Satoh F, Umemura S, Osamura RY. Immunohistochemical analysis of GCDFP-15 and GCDFP-24 in mammary and non-mammary tissue. Breast Cancer. 2000 Jan;7(1):49-55.
  9. Striebel JM, Dacic S, Yousem SA. Gross cystic disease fluid protein-(GCDFP-15): expression in primary lung adenocarcinoma. Am J Surg Pathol. 2008 Mar;32(3):426-32.
  10. Viacava P, Naccarato AG, Bevilacqua G. Spectrum of GCDFP-15 expression in human fetal and adult normal tissues. Virchows Arch. 1998 Mar;432(3):255-60.