title: Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma.
abstract: A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC.
authors.affiliation: Laboratory of Oncobiology, School of Medicine, University of Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Russo
authors.forename: V
authors.initials: V
authors.lastname: Bazan
authors.forename: M
authors.initials: M
authors.lastname: Migliavacca
authors.forename: I
authors.initials: I
authors.lastname: Zanna
authors.forename: C
authors.initials: C
authors.lastname: Tubiolo
authors.forename: F M
authors.initials: FM
authors.lastname: Tumminello
authors.forename: G
authors.initials: G
authors.lastname: Dardanoni
authors.forename: M
authors.initials: M
authors.lastname: Cajozzo
authors.forename: P
authors.initials: P
authors.lastname: Bazan
authors.forename: G
authors.initials: G
authors.lastname: Modica
authors.forename: M
authors.initials: M
authors.lastname: Latteri
authors.forename: R M
authors.initials: RM
authors.lastname: Tomasino
authors.forename: G
authors.initials: G
authors.lastname: Colucci
authors.forename: N
authors.initials: N
authors.lastname: Gebbia
authors.forename: G
authors.initials: G
authors.lastname: Leto
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D000328:Adult; D000368:Aged; D016282:Aspartic Acid Endopeptidases / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011003:Ploidies; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D016196:S Phase; D012697:Serine Endopeptidases / Q000032:analysis*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; D016282:Aspartic Acid Endopeptidases