LUNG ADENOCARCINOMAS. CLINICOPATHOLOGICAL STUDY WITH

RESPECT TO THE UPCOMING NEW CLASSIFICATION AND EGFR-KRAS

MUTATION ANALYSIS IMPLICATIONS.

First author: Andone SebastianCo-author: Roman Adina

Coordinator: Mezei Tibor, MD

Introduction

• The incidence of lung adenocarcinoma has increased significantly – US > 50%[1]

• Adenocarcinoma surpassed squamous cell carcinoma in the last few years

• Recent histopathological and genetic studies provided an extended pathway to research

[1]Motoi, Noriko, et al. "Lung adenocarcinoma: modification of the 2004 WHO[..]." The American journal of

surgical pathology 32.6 (2008): 810-827.

• 2004 WHO Classifcation

Introduction

Travis et al “International Association for the study of Lung Cancer[..]” Journal of Thoracic Oncology, Volume 6, Number 2 February 2011 246-247

New proposed classification (WHO 2015)

• Current histological types of adenocarcinomas– Mixed subtype– Acinar– Papillary– Solid– Brochioloalveolar

• Immunohistochemical markers:– CK7, TTF1, Napsin

Introduction

Macroscopic aspects of adenocarcinoma

Microscopic aspects of adenocarcinoma

[1] [2]

[3] [4]

[1] – Acinar[3] – Papillary

[2] – Bronchioloalveolar[4] - Solid

Immunohistochemistry stains

[1] [2]

[3] [4]

[1] – TTF1[3] – CK7

[2] – TTF1[4] - CEA

• Main purpose:– To review and study adenocarcinoma lung

tumors incidence and clinicopathological features

• Specific purposes:– Obtaining a theoretical basis of EGFR-KRAS

mutation implications and the importance of their biologic and therapeutic relevance

Objective

• 140 cases registered at the Pathology Department in the 2003-2013 period

• Evaluation of clinical factors with prognostic value in the diagnosis of adenocarcinoma– Age, gender, tumor size, pathological stage,

extent of resection, histological subtype

• Evaluation 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 adenocarcinoma– High-grade adenocarcinoma

• Age and sex distribution

• Maximal size

• Location/focality

• EGFR-KRAS histopathological features

Results

• Data showed an higher incidence in men (71.40%).

• Women diagnosed with adenocarcinoma

24,6% (2003-2008)

32% (2008-2013)

Results

Results

Adenocarcinoma Squamous 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=0.18

Results

• Maximal size analysis was performed according to histological grade and data distribution to high-grade and low-grade tumors

• High grade tumors present a higher maximal size distribution (p=0.02)

Results

Results

Low grade tumors High grade tumors

Results

• 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 adenocarcinoma– Increased incidence of smoking in women – Usage of filter cigarettes [1]

– Increased incidence among young adults [2]

Discussions

[1] Hidemi Ito et al “Nonfilter and filter cigarette consumption [..]” International Journal of Cancer, Volume 128 issue 8, pages 1918–1928, 15 April 2011[2]Lung 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 .

Discussions

Finberg, Karin E., et al. "Mucinous Differentiation Correlates [..]." The Journal of Molecular Diagnostics 9.3 (2007):

320-326.

• Basic conclusions– Increased incidence of diagnosis in women [1]

– The incidence of diagnosis in young adults– The upcoming (?) 2015 WHO classification

and its possible correlation with genetic mutations

– The importance of testing for EGFR-KRAS mutation

Conclusions

[1] Ronald G.Vincent et al “ The changing histopathology of lung cancer[..]” Cancer, volume 39, Isssue 4 pages 1647-1653 June 2006

• Novelty and limitations– Complete analysis of clinicopathological features– Statistical analysis based on histological grade

comparison– Recent studies evaluation– The limitations of immunohistochemical complete

studies – The limitations concerning gene mutation analysis– National Cancer Registry limitations

Conclusions