Tumor-associated immune cell infiltrate density in penile squamous cell carcinomas

Penile squamous cell carcinomas are rare tumor entities throughout Europe. Early lymphonodal spread urges for aggressive therapeutic approaches in advanced tumor stages. Therefore, understanding tumor biology and its microenvironment and correlation with known survival data is of substantial interest in order to establish treatment strategies adapted to the individual patient. Fifty-five therapy naïve squamous cell carcinomas, age range between 41 and 85 years with known clinicopathological data, were investigated with the use of tissue microarrays (TMA) regarding the tumor-associated immune cell infiltrate density (ICID). Slides were stained with antibodies against CD3, CD8 and CD20. An image analysis software was applied for evaluation. Data were correlated with clinicopathological characteristics and overall survival. There was a significant increase of ICID in squamous cell carcinomas of the penis in relation to tumor adjacent physiological tissue. Higher CD3-positive ICID was significantly associated with lower tumor stage in our cohort. The ICID was not associated with overall survival. Our data sharpens the view on tumor-associated immune cell infiltrate in penile squamous cell carcinomas with an unbiased digital and automated cell count. Further investigations on the immune cell infiltrate and its prognostic and possible therapeutic impact are needed.

A Web-Based Prediction Model for Cancer-Specific Survival of Elderly Patients With Hypopharyngeal Squamous Cell Carcinomas: A Population-Based Study

Background: Hypopharyngeal squamous cell carcinomas (HPSCC) is one of the causes of death in elderly patients, an accurate prediction of survival can effectively improve the prognosis of patients. However, there is no accurate assessment of the survival prognosis of elderly patients with HPSCC. The purpose of this study is to establish a nomogram to predict the cancer-specific survival (CSS) of elderly patients with HPSCC.Methods: The clinicopathological data of all patients from 2004 to 2018 were downloaded from the SEER database. These patients were randomly divided into a training set (70%) and a validation set (30%). The univariate and multivariate Cox regression analysis confirmed independent risk factors for the prognosis of elderly patients with HPSCC. A new nomogram was constructed to predict 1-, 3-, and 5-year CSS in elderly patients with HPSCC. Then used the consistency index (C-index), the calibration curve, and the area under the receiver operating curve (AUC) to evaluate the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to assess the clinical value of the model.Results: A total of 3,172 patients were included in the study, and they were randomly divided into a training set (N = 2,219) and a validation set (N = 953). Univariate and multivariate analysis suggested that age, T stage, N stage, M stage, tumor size, surgery, radiotherapy, chemotherapy, and marriage were independent risk factors for patient prognosis. These nine variables are included in the nomogram to predict the CSS of patients. The C-index for the training set and validation was 0.713 (95% CI, 0.697–0.729) and 0.703 (95% CI, 0.678–0.729), respectively. The AUC results of the training and validation set indicate that this nomogram has good accuracy. The calibration curve indicates that the observed and predicted values are highly consistent. DCA indicated that the nomogram has a better clinical application value than the traditional TNM staging system.Conclusion: This study identified risk factors for survival in elderly patients with HPSCC. We found that age, T stage, N stage, M stage, tumor size, surgery, radiotherapy, chemotherapy, and marriage are independent prognostic factors. A new nomogram for predicting the CSS of elderly HPSCC patients was established. This model has good clinical application value and can help patients and doctors make clinical decisions.

BIRC2–BIRC3 amplification: a potentially druggable feature of a subset of head and neck cancers in patients with Fanconi anemia

Head-and-neck squamous cell carcinomas (HNSCCs) are relatively common in patients with Fanconi anemia (FA), a hereditary chromosomal instability disorder. Standard chemo-radiation therapy is not tolerated in FA due to an overall somatic hypersensitivity to such treatment. The question is how to find a suitable alternative treatment. We used whole-exome and whole genome mRNA sequencing to identify major genomic and transcriptomic events associated with FA-HNSCC. CRISPR-engineered FA-knockout models were used to validate a number of top hits that were likely to be druggable. We identified deletion of 18q21.2 and amplification of 11q22.2 as prevailing copy-number alterations in FA HNSCCs, the latter of which was associated with strong overexpression of the cancer-related genes YAP1, BIRC2, BIRC3 (at 11q22.1-2). We then found the drug AZD5582, a known small molecule inhibitor of BIRC2-3, to selectively kill FA tumor cells that overexpressed BIRC2-3. This occurred at drug concentrations that did not affect the viability of untransformed FA cells. Our data indicate that 11q22.2 amplifications are relatively common oncogenic events in FA-HNSCCs, as holds for non FA-HNSCC. Therefore, chemotherapeutic inhibition of overexpressed BIRC2-3 may provide the basis for an approach to develop a clinically realistic treatment of FA-HNSCCs that carry 11q22.2 amplifications.

Gene of the month: Cornulin

Cornulin (CRNN) gene encodes a 495 amino acid long protein and is located on chromosome 1q21.3. Primarily, it functions as the marker of differentiation. Initially, it was found to be specific for the squamous cells of oesophagus. However, later on, several studies have revealed the presence of Cornulin downregulation in various epithelial squamous cell carcinomas of the head and neck, oesophagus and cervix and clinically associated it with worsening of cancer and the poor prognosis. Cornulin levels also showed dysregulation in other diseases such as Eczema and Psoriasis. Besides the differentiation marker, it was identified to be involved in the stress response. The studies, in psoriasis and oesophageal squamous cell carcinoma, has elucidated that the dysregulation in the Cornulin is associated with the cell cycle events such as G1/S transition. However, the actual function of Cornulin is still yet to be explored in detail.

Research on Anal Squamous Cell Carcinoma

Anal canal and peri-anal squamous cell carcinomas (ASCCs) are relatively rare cancers that affect approximately 8000 patients per year in the United States [...]

A Study of Prognostic Factors in Young Patients With Non-HPV Oral Cancer in Central Europe

The etiological factors of squamous cell carcinomas of the head and neck have been well known for a long time. It is also well known that the incidence of oral cancer diagnosed in younger patients is on the rise. Due to the young age of these patients, the increase in the number of these cases and the fact that many of them neither smoke nor drink alcohol it has been suggested that other factors might be at play in the carcinogenesis of oral cancer. Thus, along the classic etiological factors of smoking and alcohol abuse certain molecular marker anomalies and the human papilloma virus (HPV) have emerged as potential factors. The aim of the present study is to verify the potential prognostic factors and to map the differences in biomarker expression between the young and the old patient groups. In the present study the immunohistochemical profile of samples obtained from oral squamous cell carcinomas was studied and compared with various clinico-pathological parameters. In 88 samples the expressions of p16, p53, Ki67, EGFR were studied with a tissue microarray technique under standard reaction conditions as well as the detection and typing of HPV infection with the Full Spectrum HPV DNA method. The biomarker expression profile of young patients with oral squamous cell carcinoma was compared to that of older patients (above 50). A significant difference was found between the immunohistochemical profile of the young and old patient groups in p16, Ki67 expression. The overall survival and progression free survival were influenced by p16 expression in young age.