scholarly journals TTF-1/p63-Positive Poorly Differentiated NSCLC: A Histogenetic Hypothesis from the Basal Reserve Cell of the Terminal Respiratory Unit

Diagnostics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Daniela Cabibi ◽  
Sandro Bellavia ◽  
Antonino Giulio Giannone ◽  
Nadia Barraco ◽  
Calogero Cipolla ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Small Cell Lung Carcinoma ◽  
Alveolar Epithelium ◽  
Small Cell ◽  
Specific Marker ◽  
Basal Cells ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Poorly Differentiated

TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (ΔNp63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast.

scholarly journals Histopathological subtypes of lung cancer presented at a tertiary care cancer hospital in Kerala: a cross sectional study

2020 ◽  
Vol 8 (1) ◽  
pp. 11
Author(s):  
Sourabh Radhakrishnan ◽  
Sreeja Raju ◽  
Jamuna Angel Joy ◽  
Sanjana Ramakrishnan
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Clinical Presentation ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Histological Subtype ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Significant Difference

Background: Lung cancer is one of the commonest cancers causes high rate of mortality worldwide. An increasing incidence of lung cancer and the pathological profile varies among gender and geographical regions. The present study was aimed to assess the pattern of histological subtypes of lung cancer and their distribution with age and gender.Methods: Histologically proven primary lung cancers were selected from the cancer registry. Distribution of subtypes of lung cancer in various age and gender was collected. The major clinical presentation among the non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) were also analysed. The data were statistically analysed.Results: A total of 155 cases of lung cancers were analysed. Adenocarcinoma of lung was the most common subtype followed by squamous cell carcinoma and SCLC. Majority were males with age of presentation from 23 to 93 years. Age of presentation in the female group was 23-75 years. Significant difference was found between cancer numbers in male and female patients (p=0.0001). Statistically significant difference was found among the distribution of smokers and non-smokers in the NSCLC and SCLC patients (p=0.046). Most of the NSCLC and SCLC patients were presented with dyspnea and coughing.Conclusions: Lung cancers were commonly seen in males and smokers. The most common histological subtype in males and females was adenocarcinoma. The diagnosis of histological subtype at the onset of clinical presentation of suspected cases of lung cancer is required to start the therapeutic regimen at the earliest to increase the longevity of patients.

scholarly journals Exploring the prognostic value of SCARF1 in non-small cell lung cancers

2021 ◽  
Author(s):  
Daniel A. Patten ◽  
Shishir Shetty
Keyword(s):  
Endothelial Cells ◽  
Prognostic Value ◽  
Therapeutic Potential ◽  
Small Cell Lung Carcinoma ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
The Cancer Genome Atlas ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Lung Cancers

AbstractScavenger receptor class F member 1 (SCARF1) has previously been shown to be highly expressed within the human liver, hold prognostic value in hepatocellular carcinoma and mediate the specific recruitment of leukocytes to liver sinusoidal endothelial cells; however, to date, the liver remains the only major organ in which SCARF1 has been explored in any detail. Here, we utilised publically-available RNA-sequencing data from The Cancer Genome Atlas (TGCA) to identify the lungs as a site of significant SCARF1 expression and attribute the majority of its expression to endothelial cell populations. Next, we show that SCARF1 expression is significantly reduced in two histologically distinct types of non-small cell lung carcinoma cancers (NSCLCs), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), compared to non-tumoural tissues. Interestingly, loss of SCARF1 expression was associated with aggressive tumour biology in LUAD tissues, but not in LUSC. Furthermore, increased SCARF1 expression was highly prognostic of better overall survival in LUAD tumour tissues, but this was again in contrast to LUSC tumours, in which SCARF1 held no prognostic value. Finally, we showed that SCARF1 is widely expressed in tumour endothelial cells of non-small cell lung cancers and that its total expression in LUAD tumour tissues correlated with immune score and CD4+ T cell infiltration. This study represents the first detailed exploration of SCARF1 expression in normal and diseased human lung tissues and further highlights the prognostic value and therapeutic potential of SCARF1 in immunologically active cancers.

scholarly journals BRAF in Lung Cancers: Analysis of Patient Cases Reveals Recurrent BRAF Mutations, Fusions, Kinase Duplications, and Concurrent Alterations

2018 ◽  
pp. 1-15 ◽  
Author(s):  
Yuri Sheikine ◽  
Dean Pavlick ◽  
Samuel J. Klempner ◽  
Sally E. Trabucco ◽  
Jon H. Chung ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Braf V600e ◽  
Small Cell Lung ◽  
Braf Mutations ◽  
Data Set ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Small Series

Purpose Dabrafenib and trametinib are approved for the management of advanced non–small-cell lung cancers (NSCLCs) that harbor BRAF V600E mutations. Small series and pan-cancer analyses have identified non-V600 alterations as therapeutic targets. We sought to examine a large genomic data set to comprehensively characterize non-V600 B RAF alterations in lung cancer. Patients and Methods A total of 23,396 patients with lung cancer provided data to assay with comprehensive genomic profiling. Data were reviewed for predicted pathogenic BRAF base substitutions, short insertions and deletions, copy number changes, and rearrangements. Results Adenocarcinomas represented 65% of the occurrences; NSCLC not otherwise specified (NOS), 15%; squamous cell carcinoma, 12%; and small-cell lung carcinoma, 5%. BRAF was altered in 4.5% (1,048 of 23,396) of all tumors; 37.4% (n = 397) were BRAF V600E, 38% were BRAF non-V600E activating mutations, and 18% were BRAF inactivating. Rearrangements were observed at a frequency of 4.3% and consisted of N-terminal deletions (NTDs; 0.75%), kinase domain duplications (KDDs; 0.75%), and BRAF fusions (2.8%). The fusions involved three recurrent fusion partners: ARMC10, DOCK4, and TRIM24. BRAF V600E was associated with co-occurrence of SETD2 alterations, but other BRAF alterations were not and were instead associated with CDKN2A, TP53, and STK11 alterations ( P < .05). Potential mechanisms of acquired resistance to BRAF V600E inhibition are demonstrated. Conclusion This series characterized the frequent occurrence (4.4%) of BRAF alterations in lung cancers. Recurrent BRAF alterations in NSCLC adenocarcinoma are comparable to the frequency of other NSCLC oncogenic drivers, such as ALK, and exceed that of ROS1 or RET. This work supports a broad profiling approach in lung cancers and suggests that non-V600E BR AF alterations represent a subgroup of lung cancers in which targeted therapy should be considered.

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