Cancer Report

Cancer : Lung: Non-small cell carcinoma
Summary
Cancer Name Lung: Non-small cell carcinoma
Description See also the overview on lung tumors Non-small cell carcinomas are divided into three main categories according to the predominant morphology of the tumour cells as determined by light microscopy. Although it is possible to distinguish different histological sub-groups in this way, or by using gene expression profiling, treatment is currently decided on the basis of tumour staging, age and performance status and is independent of tumour histology. In the future, this may change as new drugs are developed and as more information is gathered on the predictive power of such expression profiles.
 
Clinics and Pathology
Pathology Squamous cell carcinoma:
Approximately 30% of lung tumours are classified as squamous cell carcinomas (SCC). Whilst this was the most common sub-type seen in the past, the incidence of SCC appears to be decreasing relative to adenocarcinoma, probably as a consequence of historical changes in the way that cigarettes are smoked (lower tar and filter tips promoting deeper inhalation). SCC cells are large, flattened and stratified with a high cytoplasm to nucleus ratio. Key diagnostic features include the presence of intracytoplasmic keratin which may be linked to the presence of intercellular bridges and squamous pearl formation. Most SCC arise centrally within the main, lobar, segmental or subsegmental bronchi but some occur more peripherally. The tumour mass generally extends into the lumen of the airway with invasion into the underlying wall.

Adenocarcinoma:
A further 30-50% of tumours are defined as adenocarcinomas (ADC). This tumour type is the most common in non-smokers and women and it is more frequently associated with pleural effusions and distant metastases. ADC may be further sub-classified into:

  • acinar (gland forming),
  • papillary,
  • bronchioalveolar (BAC),
  • solid with mucin and
  • mixed.
    As most ADC are histologically heterogeneous, they generally fall into the mixed category. The tumours usually arise in the smaller peripheral airways (as distinct from the cartilage bearing bronchi) but they can be found more centrally. The key diagnostic features of ADC include gland formation - where the tumour cells are arranged around a central lumen - and/or mucin production. ADC is the tumour type most commonly found associated with fibrotic scars, which are thought to be caused in some way by the tumour. BAC, which represents 2-6% of total lung cancer is distinct from other sub-types both in terms of its growth pattern, which is lepidic (typically arising beyond the terminal bronchioloes, where it spreads along the alveolar septa causing minimal structural damage) and by the fact that it is non-invasive.

    Large cell carcinoma:
    Approximately 10% of NSCLC are defined as large cell carcinomas (LCC). This is a diagnosis of exclusion. Where a poorly differentiated tumour has none of the defining features of SCLC, SCC or ADC it may be classified as LCC: that is, where the cells of the lesion are not-columnar in shape, do not contain mucous, do not show squamous differentiation, and do not have neuroendocrine properties or small cell characteristics. Tumours tend to consist of large cells with abundant cytoplasm, large nuclei and prominent nucleoli and they may occur peripherally or centrally. Variants of LCC include clear cell carcinoma, giant cell carcinoma and large cell neuroendocrine carcinoma (LCNEC).

    Pre-invasive lesions
    The bronchial epithelium of the larger airways is a pseudo-stratified epidermal layer. The most frequent cell types present are ciliated columnar cells, interspersed mucous-producing goblet cells and, lying closely against the basement membrane, multi-potent basal epithelial cells. The basal (or reserve) cell has a repair capacity in that it is able to differentiate, as required, into the other mature cells of the larger conducting airways. In the smaller terminal and respiratory bronchioles, basal cells are not present. The reserve cells of these epithelia are the cuboidal, non-ciliated Clara cells. It has been suggested that the multi-potent basal cell or a stem cell precursor of such cells may represent a common lung cancer progenitor.

    In chronic smokers, the cells of the tracheo-bronchial tree are repeatedly exposed to a range of carcinogenic compounds. Consequently, histologically-recognisable reactive and pre-neoplastic changes can generally be seen scattered throughout the airways of long-time smokers. In situ (pre-invasive) carcinoma (CIS: full thickness cytological atypia, increased nuclear to cytoplasmic ratio) is a recognised precursor of squamous cell carcinoma. This is the end of a spectrum of pre-neoplastic transformation that ranges from squamous metaplasia (change in appearance of cuboidal cells towards squamous morphology) through mild to severe dysplasia (loss of polarity, increasing disorder) to CIS. A second pre-neoplastic state is represented by Atypical Adenomatous Hyperplasia (AAH). This is a bronchioalveolar proliferation of slightly atypical cuboidal cells that falls short of the criteria for BAC: it is a recognised precursor to adenocarcinoma.


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    Gene Symbol ERBB2
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    Description From COSMIC:
     
    Gene Symbol EIF2AK4
    Description From COSMIC:
     
    Gene Symbol TAF1L
    Description From COSMIC:
     
    Gene Symbol TAF1
    Description From COSMIC:
     
    Gene Symbol NTRK2
    Description From COSMIC:
     
    Gene Symbol NTRK3
    Description From COSMIC:
     
    Gene Symbol EGFR
    Description From COSMIC, cancer gene census of CGP
     
    Gene Symbol NTHL1
    Description From COSMIC:
     
    Gene Symbol TAOK1
    Description From COSMIC:
     
    Gene Symbol NTRK1
    Description From COSMIC:
     
    Gene Symbol TAOK3
    Description From COSMIC:
     
    Gene Symbol STK17B
    Description From COSMIC:
     
    Gene Symbol STK13
    Description From COSMIC:
     
    Gene Symbol N-RAS
    Description From COSMIC:
     
    Gene Symbol EDD1
    Description From COSMIC:
     
    Gene Symbol STK31
    Description From COSMIC:
     
    Gene Symbol E2F3
    Description From COSMIC:
     
    Gene Symbol DYRK4
    Description From COSMIC:
     
    Gene Symbol STK33
    Description From COSMIC:
     
    Gene Symbol DUSP23
    Description From COSMIC:
     
    Gene Symbol DOCK1
    Description From COSMIC:
     
    Gene Symbol STK6
    Description From COSMIC:
     
    Gene Symbol ACK1
    Description From COSMIC:
     
    Gene Symbol ABL2
    Description From COSMIC:
     
    Gene Symbol FGFR1
    Description From COSMIC:
     
    Gene Symbol ABL1
    Description From COSMIC census:
     
    Gene Symbol MUSK
    Description From COSMIC:
     
    Gene Symbol FGFR2
    Description From COSMIC:
     
    Gene Symbol STAG3
    Description From COSMIC:
     
    Gene Symbol FBXO6
    Description From COSMIC:
     
    Gene Symbol FBXO46
    Description From COSMIC:
     
    Gene Symbol AATK
    Description From COSMIC:
     
    Gene Symbol STK11
    Description From COSMIC, cancer gene census of CGP
     
    Gene Symbol MYCBP2
    Description From COSMIC:
     
    Gene Symbol FASTK
    Description From COSMIC:
     
    Gene Symbol FBXL7
    Description From COSMIC:
     
    Gene Symbol FBXO25
    Description From COSMIC:
     
    Gene Symbol MOS
    Description From COSMIC:
     
    Gene Symbol FBXL12
    Description From COSMIC:
     
    Gene Symbol FBXL21
    Description From COSMIC:
     
    Gene Symbol FBXO34
    Description From COSMIC:
     
    Gene Symbol SNK
    Description From COSMIC:
     
    Gene Symbol FBXO31
    Description From COSMIC:
     
    Gene Symbol FBXO40
    Description From COSMIC:
     
    Gene Symbol MRE11B
    Description From COSMIC:
     
    Gene Symbol FAM5C
    Description From COSMIC:
     
    Gene Symbol SPEN
    Description From COSMIC:
     
    Gene Symbol SPI1
    Description From COSMIC:
     
    Gene Symbol AKAP4
    Description From COSMIC:
     
    Gene Symbol NCK2
    Description From COSMIC:
     
    Gene Symbol NCOA1
    Description From COSMIC:
     
    Gene Symbol NCOA2
    Description From COSMIC:
     
    Gene Symbol NCOA3
    Description From COSMIC:
     
    Gene Symbol F9
    Description From COSMIC:
     
    Gene Symbol SMC2L1
    Description From COSMIC:
     
    Gene Symbol SMARCC2
    Description From COSMIC:
     
    Gene Symbol AKAP12
    Description From COSMIC:
     
    Gene Symbol SMARCD3
    Description From COSMIC:
     
    Gene Symbol NCOA6IP
    Description From COSMIC:
     
    Gene Symbol NCOA7
    Description From COSMIC:
     
    Gene Symbol SNF1LK
    Description From COSMIC:
     
    Gene Symbol ADRBK2
    Description From COSMIC:
     
    Gene Symbol NEK1
    Description From COSMIC:
     
    Gene Symbol SMYD1
    Description From COSMIC:
     
    Gene Symbol NEK10
    Description From COSMIC:
     
    Gene Symbol SMURF2
    Description From COSMIC:
     
    Gene Symbol ERN2
    Description From COSMIC:
     
    Gene Symbol ADH7
    Description From COSMIC:
     
    Gene Symbol NEK7
    Description From COSMIC:
     
    Gene Symbol ADRA2B
    Description From COSMIC:
     
    Gene Symbol ADPRT
    Description From COSMIC:
     
    Gene Symbol ADAMTS20
    Description From COSMIC:
     
    Gene Symbol SMARCA4
    Description From COSMIC:
     
    Gene Symbol ADAMTS2
    Description From COSMIC:
     
    Gene Symbol ADAMTSL1
    Description From COSMIC:
     
    Gene Symbol MYLK2
    Description From COSMIC:
     
    Gene Symbol SLK
    Description From COSMIC:
     
    Gene Symbol MYO3B
    Description From COSMIC:
     
    Gene Symbol SLC4A10
    Description From COSMIC:
     
    Gene Symbol ERN1
    Description From COSMIC:
     
    Gene Symbol ADAMTS1
    Description From COSMIC:
     
    Gene Symbol ERK8
    Description From COSMIC:
     
    Gene Symbol ADAMTS16
    Description From COSMIC:
     
    Gene Symbol SK681
    Description From COSMIC:
     
    Gene Symbol MYOC
    Description From COSMIC:
     
    Gene Symbol ADAMTS15
    Description From COSMIC:
     
    Gene Symbol MYST2
    Description From COSMIC:
     
    Gene Symbol ERC1
    Description From COSMIC:
     
    Gene Symbol ADAM2
    Description From COSMIC:
     
    Gene Symbol N4BP2
    Description From COSMIC:
     
    Gene Symbol ERBB4
    Description From COSMIC:
     
    Gene Symbol ADAM32
    Description From COSMIC:
     
    Gene Symbol NALP1
    Description From COSMIC:
     
    Gene Symbol ACO2
    Description From COSMIC:
     
    Cytogenetics
    Cytogenetics Morphological The generally low mitotic index of lung carcinomas makes karyotypic analysis difficult. However, common numerical changes observed include the losses of chromosomes 9 and 13 and trisomy for chromosome 7. Unbalanced rearrangements have been reported to occur frequently within chromosomes 1, 3, 5, 6, 7, 8, 9, 11, 13, 14, 15, 17 and 19 and it is thought that the loss of genetic material due to such events might encompass, to some lesser extent, all chromosome arms. Arms which frequently show clear loss include; 9p, 3p,6q, 8p, 9q, 13q, 17p, 18q, 19p, 21q, and 22q with those often associated with gains being 7p, 7q, 1q, 3q, 5p, 11q and 12q.
    Cytogenetics Molecular Comparative genomic hybridisation (CGH) has been used to extend conventional karyotypic analysis in NSCLC. Prominent imbalances seen in several studies include losses of 3p, 8p, 9p, 13q and 17p and gain of chromosome arms 1q, 3q, 5p and 8q. Regional amplification has been reported for 3q26, 8q24, 3q13, 3q28-qter, 7q11.2, 8p11-12, 12p12 and 19q13.1-13.2. Minimally localised under-represented regions include 3p14-21, 8p21-23 and 17p12-13. CGH analysis has also suggested that some alterations are more commonly seen in particular NSCLC sub-types with gain of 3q24-qter more common in SCC than ADC and gain of 1q22-32 more common in ADC than SCC.
     
    Bibliography
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    Source and Citation
    Source Atlas of Genetics and Cytogenetics in Oncology and Haematology
    Citation Heighway J, Betticher DC . Lung: Non-small cell carcinoma. Atlas Genet Cytogenet Oncol Haematol. February 2004 .
    URL : http://AtlasGeneticsOncology.org/Tumors/LungNonSmallCellID5141.html
    URL http://AtlasGeneticsOncology.org/Tumors/LungNonSmallCellID5141.html