title: Expression of P-glycoprotein and metallothionein in gastrointestinal stromal tumor and leiomyosarcomas. Clinical implications.
abstract: We investigated the expression of P-glycoprotein (P-GP) and metallothionein (MT) in a series of 92 GIST and 14 gastrointestinal leiomyosarcomas (GILMS) with the purpose to expand our knowledge on the biological bases of GIST chemo-resistance and to ascertain their significance in patients' prognosis. P-GP expression was more frequent in GIST than in GI-LMS (83.7% vs. 21.4%, p<0.001), with no difference between low- and high-risk GIST (p=1.000) or low- and high-grade GI-LMS (p=0.538). P-GP expression was unrelated to anatomic location (gastric vs. intestinal) in GIST (39/45 vs. 35/43, p=0.770) and in GI-LMS (0/2 vs. 2/6, p=1.000). MT expression was non-significantly higher in GI-LMS than in GIST (35.7% vs. 14.1%, p=0.060), with no difference between low- and high-risk GIST (p=1.000) or low- and high-grade GI-LMS (p=1.000). MT expression was unrelated to the anatomic location (gastric vs. intestinal) in GIST (7/45 vs. 6/43) and GI-LMS (0/2 vs. 1/6) (p=1.000 and p=0.1000, respectively). Overall tumor-specific survival (p< 0.001) and disease-free survival (p<0.001) were different in GIST as compared with GI-LMS, and the number of events was higher in GI-LMS. When the survival analysis took into consideration P-GP or MT expression, the overall survival in GIST was influenced by the expression of MT (p=0.021) but not by that of P-GP (p=0.638). However, in GI-LMS, P-GP expression influenced disease-free survival (p=0.050); in addition, it is important to recognize the limited value of these results because of the low number of cases involved in the study. Differential expression of P-GP and MT might explain the known variability in response to systemic chemotherapy in these tumors. Detection of P-GP and MT seems to add certain prognostic value in GIST (MT) or GI-LMS (P-GP).
authors.affiliation: Pathology Service, Juan Ramón Jiménez Hospital, Huelva, Spain.
authors.forename: Sofia
authors.initials: S
authors.lastname: Pérez-Gutiérrez
authors.forename: Ricardo
authors.initials: R
authors.lastname: González-Cámpora
authors.forename: Joaquín
authors.initials: J
authors.lastname: Amérigo-Navarro
authors.forename: Antonio
authors.initials: A
authors.lastname: Beato-Moreno
authors.forename: María
authors.initials: M
authors.lastname: Sánchez-León
authors.forename: Jesús María
authors.initials: JM
authors.lastname: Pareja Megía
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Virizuela-Echaburu
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Beltrán
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007890:Leiomyosarcoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008668:Metallothionein