Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising.

Lung cancer rates have peaked among men in many areas of the world, but rates among women continue to rise. Most lung cancers are squamous cell carcinoma, small cell carcinoma, or adenocarcinoma; trends vary according to type. We compiled population-based morphology-specific incidence data from registries contributing to the International Agency for Research on Cancer (IARC) databases. Unspecified cancers and carcinomas were reallocated based on a registry, time period, sex and age group-specific basis. Where available, data from several registries within a country were pooled for analysis. Rates per 100,000 person-years for 1980-1982 to 1995-1997 were age-adjusted by the direct method using the world standard. Squamous cell carcinoma rates among males declined 30% or more in North America and some European countries while changing less dramatically in other areas; small cell carcinoma rates decreased less rapidly. Squamous and small cell carcinoma rates among females generally rose, with the increases especially pronounced in the Netherlands and Norway. In contrast, adenocarcinoma rates rose among males and females in virtually all areas, with the increases among males exceeding 50% in many areas of Europe; among females, rates also rose rapidly and more than doubled in Norway, Italy and France. Rates of all lung cancer types among women and adenocarcinoma among men continue to rise despite declining cigarette use in many Western countries and shifts to filtered/low-tar cigarettes. Renewed efforts toward cessation and prevention are mandatory to curb the prevalence of cigarette smoking and to reduce lung cancer rates eventually

12-0-Tetradecanoyl phorbol-13-acetate induced differentiation in human lung squamous carcinoma cells.

Three human lung squamous carcinoma cell lines (NX002, CX140 and CX143) demonstrate features of squamous differentiation including involucrin synthesis and competence to form cornified envelopes. 12-O-Tetradecanoylphorbol 13-acetate inhibits growth of these cell lines and this growth inhibition is associated with enhanced differentiation

Oral squamous cell carcinoma of tongue: Histological risk assessment. A pilot study

Background: More than 90% of malignant tumors diagnosed in the oral cavity are Oral Squamous Cell Carcinomas (OSCC) whose preferred location is the tongue. Classically, this disease has affected men preferentially, although recent studies suggest that trends are changing and the proportion of women with OSCC is increasing. In addition, the prevalence of oral cancer is also determined by some risk factors as alcohol consumption and tobacco. Currently, the Tumor, Node, Metastasis (TNM) classification is employed to defined tumor stage and based on this guide specific treatments are established. However, 5-year-survival does not exceed 50% of cases. The objective of this study is to determine whether a histological risk pattern indicative of higher recurrence might be present in T1-T2 tumors located in the anterior two thirds of the tongue. Material and Methods: Samples from 26 patients with OSCC were analyzed and histological risk pattern of recurrent and non-recurrent tumors were compared. We have analyzed histological variables described in Anneroth and Brandwein-Gensler classifications. Additionally, we have also examined both clinical variables such as age, sex or comorbidities, as well as habits such as tobacco or alcohol consumption. Results: We found that sex (male) and keratinization degree (high or moderate) are directly related with OSCC recurrence. In fact, free illness time is lower in men and higher in those cases with minimal or no keratinization. Conclusions: Based on the variables analyzed, it has not been possible to establish a histological risk pattern that, complementary to the TNM classification, could have a predictive role in these early-stage tongue carcinoma

Targeting phosphoinositide 3-kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC).

The landscape of head and neck squamous cell carcinoma (HNSCC) has been changing rapidly due to growing proportion of HPV-related disease and development of new therapeutic agents. At the same time, there has been a constant need for individually tailored treatment based on genetic biomarkers in order to optimize patient survival and alleviate treatment-related toxicities. In this regard, aberrations of PI3K pathway have important clinical implications in the treatment of HNSCC. They frequently constitute 'gain of function' mutations which trigger oncogenesis, and PI3K mutations can also lead to emergence of drug resistance after treatment with EGFR inhibitors. In this article, we review PI3K pathway as a target of treatment for HNSCC and summarize PI3K/mTOR inhibitors that are currently under clinical trials. In light of recent advancement of immune checkpoint inhibitors, consideration of PI3K inhibitors as potential immune modulators is also suggested

The immunohistochemical expression of leptin in lymph node metastasis from laryngeal squamous cell carcinoma (SCC)

Introduction: Leptin is a proteohormone produced predominantly by white adipocytes and primarily known for its key role in the control of food intake and sense of satiety. From its discover leptin has been found in different body districts, involved in always new functions and processes. In the last years numerous relationships between leptin and cancer has been found. The aim of this study is to test the leptin positivity in human primitive laryngeal squamous cell carcinoma (SCC) and in its lymph node metastasis. Materials and methods: Leptin positivity was detected by immunohistochemical analysis on pathological samples from 18 patients subjected to laryngectomy and neck dissection for SCC. Results: During the study we pointed out a statistically significant relationship (p < 0.05) between leptin positivity levels and tumor differentiation grade, in particular we observed that a decrease in tumor leptin production correlates with higher level of cancer histological dedifferentiation. Conclusion: Our research on leptin expression in laryngeal squamous neoplastic pathology is aimed to the attempt of establishing a more precise patient risk stratification thanks to a new marker able to give a contribution to the identification of patient with poor prognosis and at risk of failure of actual standard therapy

Some considerations on the WHO Histological classification of laryngeal neoplasms

A new edition of the World Health Organization (WHO) Histological classification of tumours of the hypopharynx, larynx, trachea and parapharyngeal space was published in 2017. We have considered this classification regarding laryngeal neoplasms and discuss the grounds for said revision. Many of the laryngeal neoplasms described in the literature and in the previous WHO edition from 2005 have been omitted from this current revision. Many are described elsewhere in the book but it may give the new generation of pathologists/surgeons/oncologists the false impression that these tumour entities do not exist in the larynx.info:eu-repo/semantics/publishedVersio

Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication.

The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal transition, metastasis and drug/immune resistance. YY1 shares many properties with cancer stem cells (CSCs) that drive tumorigenesis, metastasis and drug resistance and are regulated by overexpression of certain transcription factors, including SOX2, OCT4 (POU5F1), BMI1 and NANOG. Based on these similarities, it was expected that YY1 expression would be associated with SOX2, OCT4, BMI1, and NANOG's expressions and activities. Data mining from the proteomic tissue-based datasets from the Human Protein Atlas were used for protein expression patterns of YY1 and the four CSC markers in 17 types of cancer, including both solid and hematological malignancies. A close association was revealed between the frequency of expressions of YY1 and SOX2 as well as SOX2 and OCT4 in all cancers analyzed. Two types of dynamics were identified based on the nature of their association, namely, inverse or direct, between YY1 and SOX2. These two dynamics define distinctive patterns of BMI1 and OCT4 expressions. The relationship between YY1 and SOX2 expressions as well as the expressions of BMI1 and OCT4 resulted in the classification of four groups of cancers with distinct molecular signatures: (1) Prostate, lung, cervical, endometrial, ovarian and glioma cancers (YY1(lo)SOX2(hi)BMI1(hi)OCT4(hi)) (2) Skin, testis and breast cancers (YY1(hi)SOX2(lo)BMI1(hi)OCT4(hi)) (3) Liver, stomach, renal, pancreatic and urothelial cancers (YY1(lo)SOX2(lo)BMI1(hi)OCT4(hi)) and (4) Colorectal cancer, lymphoma and melanoma (YY1(hi)SOX2(hi)BMI1(lo)OCT4(hi)). A regulatory loop is proposed consisting of the cross-talk between the NF-kB/PI3K/AKT pathways and the downstream inter-regulation of target gene products YY1, OCT4, SOX2 and BMI1