title: A Histopathological Feature of EGFR-Mutated Lung Adenocarcinomas with Highly Malignant Potential - An Implication of Micropapillary Element.
abstract: The purpose of this study was to define histological features determining the malignant potential of EGFR-mutated lung adenocarcinoma (LADC). Surgically resected tumors (EGFR-mutated LADCs with (21) and without (79) lymph node metastasis and EGFR wild-type LADCs with (26) and without (108) lymph node metastasis) and biopsy samples from inoperably advanced tumors (EGFR-mutated LADCs (78) and EGFR wild-type LADCs (99)) were examined. In surgically resected tumors, the EGFR-mutated LADCs with lymph node metastasis had the micropapillary element in a significantly greater proportion than others (Mann-Whitney tests P ≤0.026). The proportion of micropapillary element was higher in the EGFR-mutated LADC at the advanced stage (stage II, III, or IV) than in the tumor at the early stage (stage I) (Mann-Whitney test, P<0.0001). In the biopsy samples from inoperably advanced LADCs (177), EGFR-mutated tumors also had micropapillary element at a higher frequency than EGFR-wild type tumors (53/78 (68%), versus 30/99 (30%), Pearson x2 test, P<0.0001). In stage I EGFR-mutated LADCs (84), the tumors with the micropapillary element (34) exhibited a significantly higher recurrence rate than tumors without micropapillary element (50) (5-year Recurrence-free survival 64.4% versus 93.3%, log-rank test P = 0.028). The micropapillary element may be an exclusive determinant of malignant potential in EGFR-mutated LADC. It is suggested that EGFR-mutated LADC may develop through a distinct histogenesis, in which the micropapillary element is important for promoting progression.
authors.affiliation: Department of Pathology, Yokohama City University, School of Medicine, Yokohama, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Matsumura
authors.affiliation: Department of Pathology, Yokohama City University, School of Medicine, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Okudela
authors.affiliation: Department of Pathology, Yokohama City University, School of Medicine, Yokohama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Department of Pathology, Yokohama City University, School of Medicine, Yokohama, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Umeda
authors.affiliation: Department of Pathology, Yokohama City University, School of Medicine, Yokohama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tateishi
authors.affiliation: Division of Respiratory Medicine, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Yokohama, Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Division of Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Yokohama, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Arai
authors.affiliation: Division of Surgery, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japan.
authors.forename: Tetsukan
authors.initials: T
authors.lastname: Woo
authors.affiliation: Division of Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Yokohama, Japan.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Tajiri
authors.affiliation: Department of Pathology, Yokohama City University, School of Medicine, Yokohama, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D047368:Tumor Burden
chemical_list: D066246:ErbB Receptors