Premium
Differential subcellular localisation of the tumour suppressor protein LIMD1 in breast cancer correlates with patient survival
Author(s) -
Spendlove Ian,
AlAttar Ahmad,
Watherstone Oliver,
Webb Thomas M.,
Ellis Ian O.,
Longmore Gregory D.,
Sharp Tyson V.
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23851
Subject(s) - tissue microarray , breast cancer , pathology , subcellular localization , immunohistochemistry , cytoplasm , cancer , lymph node , medicine , biology , cancer research , microbiology and biotechnology
The tumour suppressor gene (TSG) LIM domain containing protein 1 ( LIMD1 ) has been associated with transformation of epithelial cells of the lung and its expression is downregulated in all lung tumour samples tested compared to normal lung matched controls. In the first study of its kind we used an anti‐LIMD1 specific monoclonal antibody to investigate expression/localisation of the LIMD1 protein in a well‐characterised tissue microarray of breast cancers and normal adjacent epithelia. Comparison of tumour with adjacent normal and distant normal tissue demonstrated that LIMD1 expression is moderate to high compared to tumour. There was also a significant correlation with histological grade ( p = 0.0001), tumour size ( p = 0.013) and tumour type ( p = 0.004) indicating an association with aggressive disease. Cytoplasmic LIMD1 expression was seen in 99.3% of cases, with 43.1% showing both nuclear and cytoplasmic localisation. Absence/loss of nuclear staining showed a strong correlation with patient survival and was indicative of poor prognosis ( p = 0.033). There was no association with lymph node status and other clinicopathological parameters. Nuclear staining was more pronounced in better prognosis tumours and normal tissue. This study demonstrates that LIMD1 represents a novel prognostic marker for breast cancer. Combined with the fact that LIMD1 expression is downregulated in lung cancers this clearly indicates that LIMD1 may represent a critical TSG, the function of which is deregulated via overall loss of expression and/or relocalisation within the cell during tumour development. The possible functions of LIMD1 localisation within the nucleus and cytoplasm and its relationship to tumour prognosis are discussed. © 2008 Wiley‐Liss, Inc.