title: Tumor islands in resected early-stage lung adenocarcinomas are associated with unique clinicopathologic and molecular characteristics and worse prognosis.
abstract: Tumor islands-large collections of tumor cells isolated within alveolar spaces-can be seen in lung adenocarcinomas. Recently we observed by 3-dimensional reconstruction that these structures were connected with each other and with the main tumor in different tissue planes, raising the possibility of tumor islands being a means of extension. However, the clinical and prognostic significance of tumor islands remains unknown. In this study, we compared clinicopathologic and molecular characteristics and prognosis of stages I to II lung adenocarcinomas with tumor islands (n=58) and those without (n=203). Lung adenocarcinomas with tumor islands were more likely to occur in smokers, exhibit higher nuclear grade and a solid or micropapillary pattern of growth, and harbor KRAS mutations. In contrast, lung adenocarcinomas without tumor islands were more likely to present as minimally invasive adenocarcinoma, show a lepidic pattern of growth, and harbor EGFR mutations. Although there was no difference in stage, the prognosis of lung adenocarcinomas with tumor islands was significantly worse than those without. The 5-year recurrence-free survival for patients with tumor islands and those without was 44.6% and 74.4%, respectively (log rank P=0.010). The survival difference remained significant (P <0.020) by multivariate analysis, and the presence of tumor islands was associated with almost 2-fold increase in the risk of recurrence. Even in the stage IA cohort, more than half of the patients with tumor islands experienced recurrence within 5 years. Thus, aggressive surveillance and/or further intervention may be indicated for patients whose tumors exhibit tumor islands.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Maristela L
authors.initials: ML
authors.lastname: Onozato
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Kovach
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: Vicente
authors.initials: V
authors.lastname: Morales-Oyarvide
authors.forename: Veronica E
authors.initials: VE
authors.lastname: Klepeis
authors.forename: Swathi
authors.initials: S
authors.lastname: Tammireddy
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Heist
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Mark
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Yukako
authors.initials: Y
authors.lastname: Yagi
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011650:Pulmonary Alveoli / Q000473:pathology; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins