Caveolin-1, CAV-1

Caveolin-1 is a 22 kDa membrane protein which is expressed by mesenchymal cells.  It is a structural component of caveolae, 80 to 100 nm omega-shaped vesicular invaginations of the plasma membrane2,3.  It has putative functions in vesicular transport, cholesterol homeostasis, cell migration, cell cycle and cell polarity regulation.  It is commonly up-regulated in malignant neoplasms.  Cav1 has been variously reported to impact both positively and negatively on various aspects of tumour progression, being both reported to function as a tumour suppressor and identified as a poor prognostic factor in various human cancers4,5.  It reportedly expression correlates with drug resistance and a poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy10.  However, it is also said to be down-regulated in human lung carcinoma, acting as a candidate tumour suppressor gene11.  Caveolin-1  is also thought to play an important roles in organogenesis6 and atherosclerosis7.

Immunohistochemical expression

In lung carcinomas, staining is predominantly membrane with cytoplasmic staining in a minority of cases12.  There is variation in the rate of expression with subtype.  Primary tumours showing metastatic spread are more often positive for caveolin-1.  Brain but not adrenal metastases may acquire positivity where the primary lung tumour was negative12.

  Subtype of lung tumour All primary tumours Primary tumours with metastatic behaviour Primary tumours without metastatic behaviour  
Adenocarcinoma 6/7012 5/5212 1/1812
Pure bronchoalveolar carcinoma 0/1212   0/1212
Squamous cell carcinoma 8/2712 6/2012 2/712
Large cell carcinoma 3/712 3/712  
Large cell neuroendocrine carcinoma 1/512 1/512  

  Status of primary lung tumour Brain metastasis Adrenal metastasis  
  Caveolin negative Caveolin positive Caveolin negative Caveolin positive
Caveolin negative 1612 1112 912 012
Caveolin positive 012 712 012 112


Diagnostic utility

Differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma:

    Epithelioid mesothelioma pulmonary adenocarcinoma Sensitivity Specificity  
mesothelioma markers Caveolin-1 80/801 6/801, 6/7012 100%1 93%1
Calretinin 79/801 14/801 99%1 83%1
D2-40 74/801 13/801 93%1 84%1
Thrombomodulin 34/421 8/801 81%1 90%1
Mesothelin 39/431 16/801 91%1 80%1
WT-1 26/431 6/801 61%1 93%1
lung adenocarcinoma markers CEA 0/801 77/801 100%1 96%1
TTF-1 0/801 69/801 100%1 86%1
SPA 0/801 73/801 100%1 91%1
Napsin-A 0/801 72/801 100%1 90%1



1 Amatya, V. J., Y. Takeshima, et al. (2009). "Caveolin-1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinoma." Histopathology 55(1): 10-19.

2 Glenney, J. R., Jr. and D. Soppet (1992). "Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts." Proc Natl Acad Sci U S A 89(21): 10517-10521.

3 Rothberg, K. G., J. E. Heuser, et al. (1992). "Caveolin, a protein component of caveolae membrane coats." Cell 68(4): 673-682.

4 Goetz, J. G., P. Lajoie, et al. (2008). Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer Metastasis Rev 27(4): 715-735.

5 Quest, A. F., J. L. Gutierrez-Pajares, et al. (2008). "Caveolin-1: an ambiguous partner in cell signalling and cancer." J Cell Mol Med 12(4): 1130-1150.

6 Fang, P. K., K. R. Solomon, et al. (2006). Caveolin-1alpha and -1beta perform nonredundant roles in early vertebrate development. Am J Pathol 169(6): 2209-2222.

7 Frank, P. G., S. E. Woodman, et al. (2003). Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol 23(7): 1161-1168.

8 Newman, G. R., L. Campbell, et al. (1999). "Caveolin and its cellular and subcellular immunolocalisation in lung alveolar epithelium: implications for alveolar epithelial type I cell function." Cell Tissue Res 295(1): 111-120.

9 von Ruhland CJ, Campbell L, Gumbleton M, Jasani B, Newman GR. Immunolocalization of caveolin-1 in rat and human mesothelium. J Histochem Cytochem. 2004 Nov;52(11):1415-25.

10 Ho CC, Kuo SH, Huang PH, Huang HY, Yang CH, Yang PC. Caveolin-1 expression is significantly associated with drug resistance and poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy. Lung Cancer. 2008 Jan;59(1):105-10.

11 Belanger MM, Roussel E, Couet J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene. Chest. 2004 May;125(5 Suppl):106S.

12 Cassoni P, Daniele L, Maldi E, Righi L, Tavaglione V, Novello S, et al. Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases. Histopathology. 2009 Jul;55(1):20-7.

This page last revised 15.8.2009.

©SMUHT/PW Bishop