Squamous-cell carcinoma of the lungs: Is it really so different?
Introduction
Lung cancer is one of the most common cancers in men. Although overall incidence rates of lung cancer are lower in women (globally, the age-standardized incidence rate is 12.1 per 100,000 women compared with 35.5 per 100,000 men), the rates are continuing to rise in many countries.
Lung cancer can be divided into four major histological subtypes: adenocarcinoma (AC), small cell carcinoma (SCLC), large cell carcinoma (LCC), and squamous cell carcinoma (SCC). SCC is the predominant histological type in men and AC is the most common subtype in women. The incidence of SCC and SCLC is decreasing in men, while the incidence of AC is stable or slightly increasing in western countries. The incidence of all histological subtypes is increasing in women, with AC increasing at the fastest rate.
There is an active research on the AC subtype due to its therapeutic implications. However, SCC remains poorly studied due to disappointing results using new therapies and a poor prognosis in patients.
In this review, we have studied different aspects of the SCC subtype, including epidemiology, clinical features, pathology, molecular biology markers, and new therapeutic targets and treatments.
Section snippets
Etiology
Several risk factors are associated with the development of SCC. Although some of these factors are common to other histological subtypes, this section focuses on the aspects that have the greatest impact on the risk of developing SCC of the lung.
Chromosomal abnormalities
Some authors investigated an amplified gene in the 8p12 chromosome region that produces increased amounts of protein in SCC of the lung. Lockwood et al. found that ten genes in the 8p12 chromosome region were expressed at higher levels in SCC samples. One amplified gene, BRF2, was more highly expressed in and more frequently activated in bronchial carcinoma in situ and dysplastic lesions, which are two early stages of SCC that play a key role in the squamous cell lineage specificity of the
Pathology
The carcinogenesis sequence of SCC has been relatively well defined (Fig. 1). It has been shown that squamous metaplasia may progress into dysplasia and subsequently into in situ and invasive carcinoma. Serial bronchoscopy and biopsy in patients with bronchial dysplasia revealed that approximately 25% of the dysplastic lesions progressed to invasive carcinoma over a mean period of 36 months. Over 50% of patients with carcinoma in situ progressed to invasive carcinoma within 30 months [28].
SCC
Treatment
Until recently, NSCLC was treated as a single disease, despite recognition of its histologic and molecular heterogeneity. Cooke et al. examined a national database retrospectively to determine if SCC exhibited a distinct clinical behavior compared to AC of the lung following resection. A total of 7888 cases of SCC and 12,601 cases of AC were evaluated from 1998 to 2000. Survival after lobectomy for stage I and II disease was shown to be significantly reduced in SCC compared with AC (p < 0.0001)
Prognosis
A recent study using data from the Surveillance, Epidemiology and End Results (SEER) Program stratified 51,749 incident stage IV NSCLC patients (1988–2003 with follow-up through 2006) by major histologic subtype and compared the Kaplan–Meier and Cox proportional hazards methods to describe overall survival and the prognostic influence of selected patient, tumor, and treatment characteristics for each histologic subgroup. Survival was highest in patients with bronchioloalveolar adenocarcinoma
Competing interests
All the authors state that they have no conflicts of interest.
Financial disclosures
No current external funding sources for this study.
Reviewers
Dr. Antonella Brunello, MD, Istituto Oncologico Veneto, University of Padua, Medical Oncology Dept., via Gattamelata 64, I-35126 Padova, Padova, Italy.
Prof. Robert Pirker, MD, Medical University of Vienna, Division of Oncology, Dept. of Internal Medicine I, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Dra María Sereno Moyano was born in Madrid in 1975. She had a degree in Medicine in 1999 in Autonoma University in Madrid and had a fellowship in Oncology in La Paz University Hospital that was completed in 4 years. Her thesis was entitled “Inmunohistochemical expression of p53, bcl2, EPOR, Her2, Beta-catenin and E-cadherin in gastric cancer. A possible prognostic profile”. She worked as medical oncologist in La Paz Hospital and MD Anderson Hospital in Madrid. She has a master's degree in
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Histological types of lung cancer attributable to fine particulate, smoking, and genetic susceptibility
2023, Science of the Total EnvironmentCitation Excerpt :The underlying mechanisms remain largely unknown and need more investigation. It is possible that SqCC usually begins in the bronchi (the passage of the air into the lungs) where cigarette smoke passes directly (Sereno et al., 2012). Cigarette smoke induces inflammation and oxidative stress in the lung tissue, which alters the transcription and activation of protein hydrolases and their inhibitors.
Nanocarriers-mediated therapeutics as a promising approach for treatment and diagnosis of lung cancer
2021, Journal of Drug Delivery Science and TechnologyCitation Excerpt :SCC occurs as a result of changes in the morphology of chronically inflamed bronchial epithelium that leads to squamous metaplasia (SM), basal cell hyperplasia (BCH), dysplasia I–III. SCC is mainly caused by smoking; besides, other factors like exposure to heavy metals, polycyclic aromatic hydrocarbons, asbestos, radioactive substances, infectious agents, inflammation (CD3, CD4, CD8 T lymphocytes, dendritic cells, T helper cells, T regulatory cells, macrophages, and neutrophils) and gene polymorphism may also lead to the progression of SCC [19,20]. Genetic, epigenetic, oncogenic abnormalities, such as the amplification of chromosome and significant change in transcriptional regulators p63 and SOX2, also cause SCC [21].
Magnetic particle targeting for diagnosis and therapy of lung cancers
2020, Journal of Controlled ReleaseCitation Excerpt :A majority of squamous cell carcinomas (between 60% to 80%) emerge in the proximal parts of the tracheobronchial tree following a series of squamous metaplasia-dysplasia-carcinoma in situ. However, it is growingly emerging as peripheral lesions [72,73]. Central necrosis with consequent cavitation might be displayed by central and peripheral squamous cell carcinomas [74,75].
Nanotechnology in the diagnosis and treatment of lung cancer
2019, Pharmacology and TherapeuticsCitation Excerpt :NSCLC is currently diagnosed using pathological characteristics consisting of histological alterations, immunohistochemical (IHC) staining, mutational and molecular genetics analysis, and imaging techniques in order to ascertain the subtype of NSCLC, and saliently, the stage of disease progression (Ettinger et al., 2012; Travis et al., 2015). Of the different histological variants of NSCLC, ADC is the most prevalent worldwide (Tang, Schreiner, & Pua, 2014) and the incidence rate of ADC is increasing fastest in women (Sereno et al., 2012). Due to the expansive heterogeneity that exists within ADC, the disease is notoriously difficult to accurately classify.
Diagnostic Pathology: Genitourinary
2016, Diagnostic Pathology: Genitourinary<sup>18</sup>F-FDG PET/CT in evaluation of squamous cell carcinoma
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Dra María Sereno Moyano was born in Madrid in 1975. She had a degree in Medicine in 1999 in Autonoma University in Madrid and had a fellowship in Oncology in La Paz University Hospital that was completed in 4 years. Her thesis was entitled “Inmunohistochemical expression of p53, bcl2, EPOR, Her2, Beta-catenin and E-cadherin in gastric cancer. A possible prognostic profile”. She worked as medical oncologist in La Paz Hospital and MD Anderson Hospital in Madrid. She has a master's degree in Molecular Oncology in Oncology Research National Center (CNIO) in Madrid. For a very long time, she was doing research in small cell lung cancer in Molecular Biology Department in La Paz University Hospital and in Lee Moffit Cancer Center, in Tampa, Florida. For the past 4 years, she is working as medical oncologist in Infanta Sofía University Hospital, in San Sebastian de los Reyes, Madrid.
Dra Isabel Rodríguez Esteban was born in Madrid in 1972. She had a degree in Medicine in 1997 in Autonoma University in Madrid and had a fellowship in Pathology in La Paz University Hospital that was completed in 4 years. For the past 4 years, she is working as an expert pathologist in La Ruber International Clinic, Guadalajara University Hospital and as lung pathologist in Infanta Sofía University Hospital, in San Sebastian de los Reyes in Madrid.
Dr Francisco Zambrana Tébar was born in Madrid in 1976. He had a degree in Medicine in 2000 in Seville University and had a fellowship in Oncology in La Macarena University Hospital in Seville that was completed in 4 years. He is working on his thesis involving the topic of colon and lung cancer proteomic profiles. For the past 2 years, he is working as medical oncologist in Infanta Sofía University Hospital, in San Sebastian de los Reyes, Madrid.
Dra María Merino was born in Madrid in 1983. He has a degree in Medicine in 2006 in Ciudad Real University and had a fellowship in Oncology in La Paz University Hospital in Madrid that was completed in 4 years. He is working on his thesis involving the topic of lung cancer research. For the past 2 years, he is working as medical oncologist in Infanta Sofía University Hospital, in San Sebastian de los Reyes, Madrid.
Dr. César Gómez-Raposo was born in Madrid in 1980. He has a degree in 2002 in Medicine in Autonoma University in Madrid and had a fellowship in Oncology in La Paz University Hospital in Madrid that was completed in 4 years. His thesis was involved in angiogenic markers in ovarian cancer. He is developing an intense research in angiogenic markers in cancer. For the past 4 years, he is working as medical oncologist in Infanta Sofía University Hospital, in San Sebastian de los Reyes, Madrid.
Miriam López-Gómez was born in Madrid in 1980. She has a degree in 2002 in Medicine in Complutense University in Madrid and had a fellowship in Oncology n Fundación Jiménez Díaz University Hospital in Madrid that was completed in 4 years. Her thesis was involved in prognostic markers and liver metastasis. For the past 4 years, she is working as medical oncologist in Infanta Sofía University Hospital, in San Sebastian de los Reyes, Madrid.
Enrique Casado Sáenz was born in Madrid in 1970. He has a degree in Medicine in 1994 in Complutense University in Madrid and had a fellowship in Oncology in La Paz University Hospital that was completed in 4 years. His thesis is focused on children tumors. He worked as medical oncologist in La Paz Hospital and Principe de Asturias University Hospital in Madrid. During several years, he was doing research in small cell lung cancer in Molecular Biology Department in La Paz University Hospital, Alabama (USA) in genetic therapy in cancer and in San Francisco (USA) with Hannahan's group with angiogenic models. In these days, he is the chief in Medical Oncology Department in Infanta Sofía University Hospital, in San Sebastian de los Reyes, Madrid.