title: EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors.
abstract: We tested 418 neoplasms along the whole spectrum of primary lung tumor histotypes for epidermal growth factor receptor (EGFR) and K-ras mutations. Clinicopathologic data from 154 patients undergoing treatment with EGFR tyrosine kinase inhibitors (TKIs) were retrospectively studied. A scoring system assigning a score for each positive or negative characteristic (+1, female sex, nonsmoking status, adenocarcinoma histotype, Asian ethnicity, and EGFR mutation; -1, current smoker and K-ras mutation; and 0, male sex, ex-smoker, nonadenocarcinoma histotype, and no mutations) was elaborated and tested with EGFR-TKI response. Salivary gland-type, mucin-rich, and neuroendocrine tumors do not harbor EGFR mutations. A subset of nonmucinous adenocarcinomas, not necessarily of the bronchioloalveolar type, is related to EGFR mutations. Three probability groups significantly correlating with response to EGFR-TKIs were identified. Of note, the addition of molecular results did not significantly change the predictive value obtained by the combination of clinicopathologic characteristics alone in this scoring system. K-ras mutations, significantly associated with the mucin-secreting type of adenocarcinoma, consistently predict lack of response in white patients.
authors.affiliation: Section of Pathologic Anatomy, Azienda Ospedaliero-Universitaria Policlinico di Modena, Via del Pozzo, 71- 41100- Modena, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Sartori
authors.forename: Alberto
authors.initials: A
authors.lastname: Cavazza
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marchioni
authors.forename: Fausto
authors.initials: F
authors.lastname: Barbieri
authors.forename: Lucia
authors.initials: L
authors.lastname: Longo
authors.forename: Mario
authors.initials: M
authors.lastname: Bavieri
authors.forename: Bruno
authors.initials: B
authors.lastname: Murer
authors.forename: Emmanuela
authors.initials: E
authors.lastname: Meschiari
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamberi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cadioli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Luppi
authors.forename: Mario
authors.initials: M
authors.lastname: Migaldi
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008175:Lung Neoplasms / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors