Expression of C4.4A in precursor lesions of pulmonary adenocarcinoma and squamous cell carcinoma

TY - JOUR

T1 - Expression of C4.4A in precursor lesions of pulmonary adenocarcinoma and squamous cell carcinoma

AU - Jacobsen, Benedikte

AU - Santoni-Rugiu, Eric

AU - Illemann, Martin

AU - Kriegbaum, Mette Camilla

AU - Laerum, Ole Didrik

AU - Ploug, Michael

N1 - Copyright © 2011 UICC.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - The protein C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor, is a potential new biomarker in non-small cell lung cancer, with high levels of expression recently shown to correlate to poor survival of adenocarcinoma patients. In this study, C4.4A immunoreactivity in precursor lesions of lung squamous cell carcinoma and adenocarcinoma was investigated by stainings with a specific anti-C4.4A antibody. In the transformation from normal bronchial epithelium to squamous cell carcinoma, C4.4A was weakly expressed in basal cell hyperplasia but dramatically increased in squamous metaplasia. This was confined to the cell membrane and sustained in dysplasia, carcinoma in situ, and the invasive carcinoma. The induction of C4.4A already at the stage of hyperplasia could indicate that it is a marker of very early squamous differentiation, which aligns well with our earlier finding that C4.4A expression levels do not provide prognostic information on the survival of squamous cell carcinoma patients. In the progression from normal alveolar epithelium to peripheral adenocarcinoma, we observed an unexpected, distinct cytoplasmic staining for C4.4A in a fraction of atypical adenomatous hyperplasias, while most bronchioloalveolar carcinomas were negative. Likewise, only a fraction of the invasive adenocarcinomas was positive for C4.4A. With a view to the prognostic impact of C4.4A in adenocarcinoma patients, this finding might suggest that C4.4A could be an early biomarker for a possibly more malignant subtype of this disease.

AB - The protein C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor, is a potential new biomarker in non-small cell lung cancer, with high levels of expression recently shown to correlate to poor survival of adenocarcinoma patients. In this study, C4.4A immunoreactivity in precursor lesions of lung squamous cell carcinoma and adenocarcinoma was investigated by stainings with a specific anti-C4.4A antibody. In the transformation from normal bronchial epithelium to squamous cell carcinoma, C4.4A was weakly expressed in basal cell hyperplasia but dramatically increased in squamous metaplasia. This was confined to the cell membrane and sustained in dysplasia, carcinoma in situ, and the invasive carcinoma. The induction of C4.4A already at the stage of hyperplasia could indicate that it is a marker of very early squamous differentiation, which aligns well with our earlier finding that C4.4A expression levels do not provide prognostic information on the survival of squamous cell carcinoma patients. In the progression from normal alveolar epithelium to peripheral adenocarcinoma, we observed an unexpected, distinct cytoplasmic staining for C4.4A in a fraction of atypical adenomatous hyperplasias, while most bronchioloalveolar carcinomas were negative. Likewise, only a fraction of the invasive adenocarcinomas was positive for C4.4A. With a view to the prognostic impact of C4.4A in adenocarcinoma patients, this finding might suggest that C4.4A could be an early biomarker for a possibly more malignant subtype of this disease.

KW - Adenocarcinoma

KW - Carcinoma, Squamous Cell

KW - Cell Adhesion Molecules

KW - Disease Progression

KW - GPI-Linked Proteins

KW - Humans

KW - Immunohistochemistry

KW - Lung Neoplasms

KW - Precancerous Conditions

KW - Tumor Markers, Biological

U2 - 10.1002/ijc.26305

DO - 10.1002/ijc.26305

M3 - Journal article

C2 - 21792890

SN - 0020-7136

VL - 130

SP - 2734

EP - 2739

JO - International journal of cancer. Journal international du cancer

JF - International journal of cancer. Journal international du cancer

IS - 11

ER -