LUNG ADENOCARCINOMAS. CLINICOPATHOLOGICAL STUDY WITH RESPECT TO THE UPCOMING NEW CLASSIFICATION AND EGFR-KRAS MUTATION ANALYSIS IMPLICATIONS.First author: Andone SebastianCo-author: Roman AdinaCoordinator: Mezei Tibor, MD
IntroductionThe incidence of lung adenocarcinoma has increased significantly US > 50%Adenocarcinoma surpassed squamous cell carcinoma in the last few yearsRecent histopathological and genetic studies provided an extended pathway to research
Motoi, Noriko, et al. "Lung adenocarcinoma: modification of the 2004 WHO[..]."The American journal of surgical pathology 32.6 (2008): 810-827.
2004 WHO ClassifcationIntroductionTravis et al International Association for the study of Lung Cancer[..] Journal of Thoracic Oncology, Volume 6, Number 2 February 2011 246-247New proposed classification (WHO 2015)
Current histological types of adenocarcinomasMixed subtypeAcinarPapillarySolidBrochioloalveolarImmunohistochemical markers:CK7, TTF1, NapsinIntroduction
Macroscopic aspects of adenocarcinoma
Microscopic aspects of adenocarcinoma Acinar Papillary
 Bronchioloalveolar - Solid
Immunohistochemistry stains TTF1 CK7
 TTF1 - CEA
Main purpose:To review and study adenocarcinoma lung tumors incidence and clinicopathological featuresSpecific purposes:Obtaining a theoretical basis of EGFR-KRAS mutation implications and the importance of their biologic and therapeutic relevanceObjective
140 cases registered at the Pathology Department in the 2003-2013 periodEvaluation of clinical factors with prognostic value in the diagnosis of adenocarcinomaAge, gender, tumor size, pathological stage, extent of resection, histological subtypeEvaluation of parameters that may suggest possible EGFR or KRAS mutations:Necrosis, atypical glandular differentiation, mucin growth patterns
Material and method
We included the data into two groups:Low-grade adenocarcinomaHigh-grade adenocarcinomaAge and sex distributionMaximal sizeLocation/focalityEGFR-KRAS histopathological featuresResults
Data showed an higher incidence in men (71.40%).Women diagnosed with adenocarcinoma 24,6% (2003-2008) 32% (2008-2013)Results
ResultsAdenocarcinomaSquamous cell carcinoma
Increased number of women diagnosed with adenocarcinoma than squamous cell carcinoma in the same period.Mean age of diagnosis of adenocarcinoma is 59 years.Age statistical analysis between high-grade- low-grade adenocarcinoma : p=0.18Results
Maximal size analysis was performed according to histological grade and data distribution to high-grade and low-grade tumorsHigh grade tumors present a higher maximal size distribution (p=0.02)Results
ResultsLow grade tumorsHigh grade tumors
Specific EGFR-KRAS histopathological features:Necrosis (70%)Atypical glandular differentiation (35%)Mucin growth patterns (10%)
Histological type: 90% of tumors were mixed subtype Results
Possible explanations regarding the increased incidence of adenocarcinomaIncreased incidence of smoking in women Usage of filter cigarettes Increased incidence among young adults Discussions Hidemi Ito et al Nonfilter and filter cigarette consumption [..] International Journal of Cancer, Volume 128 issue 8, pages 19181928,15 April 2011Lung Cancer In Young Adults. Bourke W, Milstein D, Giura R, et al.Chest 1992;102(6):1723-1729.
Patients with EGFR mutation were most likely to be never smokers and present stage I disease and had a 90% 3 year-overall survival.Patients with KRAS mutation tumors were more likely to be former/current smokers, present with locally advanced disease and have a 65% 3 year-overall survival.
Response to treatment EGFR mutation therapy with Tyrosin Kinaze inhibitors (Erlotininb, Geftinib)In our country, the main therapy includes monoclonal antibodies treatment (Trastuzumab, Bevacizumab), which has proved its efficiency, but is surpassed nowadays in the latest studies by the efficiency of TKI of NSCLC .DiscussionsFinberg, Karin E., et al. "Mucinous Differentiation Correlates [..]." The Journal of Molecular Diagnostics 9.3 (2007): 320-326.
Basic conclusionsIncreased incidence of diagnosis in women The incidence of diagnosis in young adultsThe upcoming (?) 2015 WHO classification and its possible correlation with genetic mutationsThe importance of testing for EGFR-KRAS mutationConclusions Ronald G.Vincent et al The changing histopathology of lung cancer[..] Cancer, volume 39, Isssue 4 pages 1647-1653 June 2006
Novelty and limitationsComplete analysis of clinicopathological featuresStatistical analysis based on histological grade comparisonRecent studies evaluationThe limitations of immunohistochemical complete studies The limitations concerning gene mutation analysisNational Cancer Registry limitations