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.
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.
Sartori
Giuliana
G
Section of Pathologic Anatomy, Azienda Ospedaliero-Universitaria Policlinico di Modena, Via del Pozzo, 71- 41100- Modena, Italy.
Cavazza
Alberto
A
Sgambato
Alessandro
A
Marchioni
Alessandro
A
Barbieri
Fausto
F
Longo
Lucia
L
Bavieri
Mario
M
Murer
Bruno
B
Meschiari
Emmanuela
E
Tamberi
Stefano
S
Cadioli
Annamaria
A
Luppi
Fabrizio
F
Migaldi
Mario
M
Rossi
Giulio
G
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
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors