In pulmonary lymphangioleiomyomatosis expression of progesterone receptor is frequently higher than that of estrogen receptor

Virchows Arch. 2014 Apr;464(4):495-503. doi: 10.1007/s00428-014-1559-9. Epub 2014 Feb 26.


Lymphangioleiomyomatosis (LAM) of the lung is a rare low-grade malignancy affecting primarily women of childbearing age. LAM is characterized by the proliferation of SMA and HMB-45 positive spindle-shaped and epithelioid cells throughout the lung in the form of discrete lesions causing cystic destruction and ultimately respiratory insufficiency. LAM occurs sporadically or in patients with tuberous sclerosis complex (TSC) and is etiologically linked to mutations in the TSC1 and TSC2 genes. Although LAM cells are known to express estrogen and progesterone receptors (ER and PR, respectively), their respective expression level was never determined. Therefore, here we measured the immunohistochemical expression of ERs and PRs in a large series of pulmonary LAM cases using the Aperio Spectrum Analysis Platform. Our case series comprised open lung biopsy specimens from 20 LAM patients and lungs explanted during the course of lung transplant from 24 patients. All cases were positive for ER and PR. PR expression was statistically significantly higher than ER in 80 % of the biopsies while ER predominated only in one case. Specimens from explanted cases of LAM had relatively fewer PR-positive nuclei. As a result, PR expression was significantly higher than ER in 38 % of the cases, whereas ER predominated in 33 %. Overall, PR expression predominated in 57 % of cases and ER in 21 %. These data indicate that PR frequently prevails over ER in pulmonary LAM. LAM is unusual in its high PR/ER ratio; other female neoplasms show a definite prevalence of ER. Our findings therefore warrant further study of PR function in LAM.

MeSH terms

  • Adult
  • Estrogen Receptor alpha / biosynthesis*
  • Female
  • Humans
  • Lung / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lymphangioleiomyomatosis / genetics
  • Lymphangioleiomyomatosis / metabolism*
  • Lymphangioleiomyomatosis / pathology
  • Receptors, Progesterone / biosynthesis*


  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Receptors, Progesterone