title: Maspin - the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer - is strongly expressed in preneoplastic bronchial lesions.
abstract: Maspin, SCCA1/2 and hurpin were identified by cDNA microarray analyses as dramatically differentially expressed transcripts in primary non-small cell lung cancer (NSCLC). These sequences are located within a 10-gene serpin cluster on 18q21.3. Using comparative RT-PCR, we have investigated the expression of each of these serpins, including their flanking loci, in an independent NSCLC series. Whereas six of the genes (maspin, SCCA1, SCCA2, hurpin, megsin and pAI-2) were commonly differentially expressed in primary lesions, each significantly more often in squamous cell tumours, maspin was identified as the most frequently over-represented sequence in both squamous cell carcinoma and adenocarcinoma. Using a well-characterized monoclonal antibody, we have shown strong maspin expression in tumour protein extracts, detected multiple isoforms of the 42 kDa protein and shown that maspin is localized specifically to the tumour cells within neoplastic lesions. In contrast, most cells in non-neoplastic lung tissue appear not to express the gene, with the exception of the multipotent basal epithelial cells that line the bronchial airway. These reserve cells generally show strong predominantly nuclear localization of maspin. Strong nuclear expression of maspin within primary tumour cells is correlated with increased survival (P=0.05) and a longer remission duration (P=0.02) in resectable-staged patients. However, within the airways of cancer patients and somewhat in contrast to this observation, such expression was more frequently detected in the superficial cells of preneoplastic over non-neoplastic epithelia (P<0.0001), consistent with a role for the protein in early neoplasia.
authors.affiliation: Target Identification Group, Roy Castle International Centre for Lung Cancer Research, University of Liverpool, 200 London Rd, Liverpool L3 9TA, UK.
authors.forename: Shirley L
authors.initials: SL
authors.lastname: Smith
authors.forename: Suzanne G
authors.initials: SG
authors.lastname: Watson
authors.forename: Daniel
authors.initials: D
authors.lastname: Ratschiller
authors.forename: Mathias
authors.initials: M
authors.lastname: Gugger
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Betticher
authors.forename: Jim
authors.initials: J
authors.lastname: Heighway
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics; D015153:Blotting, Western; D001984:Bronchial Neoplasms / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000235:genetics*; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D015843:Serpins / Q000032:analysis / Q000235:genetics* / Q000502:physiology
chemical_list: D000951:Antigens, Neoplasm; D011506:Proteins; C085344:SERPIN-B5; D015843:Serpins; C051072:squamous cell carcinoma-related antigen