Maspin nuclear localization is linked to favorable morphological features in pulmonary adenocarcinoma.
Maspin, a mammary homologue of Serine Protease Inhibitors, has been shown to inhibit tumor progression and metastasis. Recently, its biological functions have been linked to its subcellular localization. Specifically, a nuclear, opposed to a combined nuclear and cytoplasmic localization has been associated with increased survival in human malignancies, including non-small cell lung cancer (NSCLC). However, it is not known whether transformation affects maspin expression during lung carcinogenesis, and whether its subcellular localization correlates with the morphological features of NSCLC. To address these questions, we studied maspin expression in a model of transformation of bronchial epithelial cells and in resected NSCLC. We found that decreased maspin accompanied chemical transformation of normal immortalized bronchial epithelial cells BEAS 2B. Immunohistochemistry revealed maspin expression to be virtually universal in NSCLC, occurring in 72/77 Adenocarcinoma (ACa), and 46/46 squamous cell carcinoma (SqCCa). SqCCa showed almost exclusively a combined nuclear-cytosolic stain. In contrast, nuclear maspin, but not combined nuclear-cytoplasmic maspin significantly correlated with low histological grade, lower proliferative rate, absence of invasion, and negative p53 stain in ACa. These data support the hypothesis that nuclear localization of maspin may stratify subtypes of NSCLC with favorable clinical-pathological features.
Lonardo
Fulvio
F
Department of Pathology, Wayne State University School of Medicine, Harper University Hospital and the Karmanos Cancer Institute, 3990 John R, Detroit, MI 48201, USA. flonardo@med.wayne.edu
Li
Xiaohua
X
Siddiq
Fauzia
F
Singh
Rajendra
R
Al-Abbadi
Moussa
M
Pass
Harvey I
HI
Sheng
Shijie
S
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015153:Blotting, Western; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics*; D015843:Serpins / Q000493:pharmacokinetics*
C085344:SERPIN-B5; D015842:Serine Proteinase Inhibitors; D015843:Serpins