59cf15474fe01d57d029a695090af9e5 pmc_30999636.pdf 402696ef98661caaeeeba940294b076271c8fc5f pmc_30999636.pdf fa2ddc46e2e78ae8af509ac14a1dc42bb97c43acf0f3d2a3b3cd82344fdf7fad pmc_30999636.pdf Title: EGFR and KRAS Mutations in the Non-Tumoral Lung. Prognosis in Patients with Adenocarcinoma Subject: Tumor recurrence is frequent and survival rates remain extremely low in lung adenocarcinoma (ADC). We hypothesize that carcinogenic factors will promote loco-regional modifications not only in the future tumor, but throughout the exposed lung. Objective: To analyze whether the most prevalent mutations observed in ADC can also be observed in the non-neoplastic lung tissue, as well as the short-term prognosis implications of this finding. Methods: Non-tumoral lung parenchyma specimens obtained during surgery from 47 patients with EGFR and/or KRAS abnormalities in their ADC tumors underwent similar genomic testing. Short-term outcomes were also recorded. Results: The same mutations were present in the tumor and the histologically normal tissue in 21.3% of patients (SM group). Although local recurrences were similar in both groups, distant metastases were more frequent in the former (60 vs. 5.4%, p < 0.001). Moreover, SM patients showed lower time-to-progression (8.5 vs. 11.7 months, p < 0.001) and disease-free survival (8.5 vs. 11.2 months, p < 0.001). COX regression showed a higher risk of progression or death (DFS) in the SM group (HR 5.94, p < 0.01]. Similar results were observed when adjusting for potential confounding variables. Conclusions: These results confirm that genetic changes are present in the apparently normal lung in many ADC patients, and this finding has prognostic implications. Keywords: Adenocarcinoma; Mutations; EGFR; KRAS; Prognosis Author: Roberto Chalela, Beatriz Bellosillo, Víctor Curull, Raquel Longarón, Sergi Pascual-Guardia, Diana Badenes-Bonet, Edurne Arriola, Albert Sánchez-Font, Lara Pijuan and Joaquim Gea Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Wed Apr 17 13:06:46 2019 CEST ModDate: Wed Apr 17 13:06:46 2019 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 7209791 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZNKTAS+URWPalladioL-Ital Type 1 Custom yes yes no 101 0 IFJLZO+URWPalladioL-Bold Type 1 Custom yes yes no 102 0 PRJKGQ+VnURWPalladioL-Bold Type 1 Custom yes yes no 103 0 RWANKE+URWPalladioL-Roma Type 1 Custom yes yes no 104 0 CIQLLF+VnURWPalladioL Type 1 Custom yes yes no 105 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yes yes yes 316 0 SYVAVM+VnURWPalladioL-Italic Type 1 Custom yes yes no 377 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-08-10 12:46:41 CEST RepresentationInformation: pmc_30999636.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-07-06 04:13:05 CEST Size: 7209791 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: ぅへばづひどねづのぴちぬぜ〴ぜ〰こづっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰こづぱふづのっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぁぬぬづぬづ〭こばづっどてどっぜ〴ぜ〰ぐぃげぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎごがぜ〴ぜ〰ごどびびふづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰いどでどぴちぬぜ〴ぜ〰ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰こづぱふづのっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぁぬぬづぬづ〭こばづっどてどっぜ〴ぜ〰ぐぃげぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎごがぜ〴ぜ〰ごどびびふづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰いどでどぴちぬぜ〴ぜ〰ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ごふねはひぜ〴ぜ〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰こづぱふづのっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぁぬぬづぬづ〭こばづっどてどっぜ〴ぜ〰ぐぃげぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎごがぜ〴ぜ〰ごどびびふづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰いどでどぴちぬぜ〴ぜ〰ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ごふねはひぜ〴ぜ〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰こづぱふづのっどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぁぬぬづぬづ〭こばづっどてどっぜ〴ぜ〰ぐぃげぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎごがぜ〴ぜ〰ごどびびふづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰いどでどぴちぬぜ〴ぜ〰ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いぎぁぜ〴ぜ〰ぅへぴひちっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぁぬぬづぬづ〭こばづっどてどっぜ〴ぜ〰ぐぃげぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎごがぜ〴ぜ〰ごどびびふづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰いどでどぴちぬぜ〴ぜ〰ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどでどぴちぬぜ〴ぜ〰ぐぃげぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰いひどぶづひぜ〴ぜ〰きふぴちぴどはのびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ごふねはひぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰きふぴちぴどはのびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎごがぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰げづっふひひづのっづぜ〴ぜ〰ちのつぜ〴ぜ〰こふひぶどぶちぬぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: いひどぶづひぜ〴ぜ〰きふぴちぴどはのびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ごふねはひぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰きふぴちぴどはのびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎごがぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰げづっふひひづのっづぜ〴ぜ〰ちのつぜ〴ぜ〰こふひぶどぶちぬぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きふぴちぴどはのびぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰ぎごがぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰げづっふひひづのっづぜ〴ぜ〰ちのつぜ〴ぜ〰こふひぶどぶちぬぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: げづっふひひづのっづぜ〴ぜ〰ちのつぜ〴ぜ〰こふひぶどぶちぬぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぁぬぴづひのちぴどぶづぜ〴ぜ〰こぴふつべぜ〴ぜ〰いづびどでのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぐはぴづのぴどちぬぜ〴ぜ〰がどねどぴちぴどはのびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Children: Item: Title: ぁぬぴづひのちぴどぶづぜ〴ぜ〰こぴふつべぜ〴ぜ〰いづびどでのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぐはぴづのぴどちぬぜ〴ぜ〰がどねどぴちぴどはのびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぐはぴづのぴどちぬぜ〴ぜ〰がどねどぴちぴどはのびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: ZNKTAS+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: ZNKTAS+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: IFJLZO+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: IFJLZO+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: 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428, 467 Annotation: Subtype: Link Rect: 434, 456, 470, 467 Annotation: Subtype: Link Rect: 316, 430, 354, 441 Annotation: Subtype: Link Rect: 249, 379, 287, 389 Annotation: Subtype: Link Rect: 293, 379, 329, 389 Annotation: Subtype: Link Rect: 343, 340, 380, 351 Annotation: Subtype: Link Rect: 387, 340, 423, 351 Annotation: Subtype: Link Rect: 186, 302, 223, 312 Annotation: Subtype: Link Rect: 267, 262, 304, 273 Annotation: Subtype: Link Rect: 76, 220, 166, 251 Annotation: Subtype: Link Rect: 234, 215, 407, 225 Checksum: d817738e Type: CRC32 Checksum: 59cf15474fe01d57d029a695090af9e5 Type: MD5 Checksum: 402696ef98661caaeeeba940294b076271c8fc5f Type: SHA-1