Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions.

Background: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI. Methods: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs.

Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils.

Objectives: To analyze the prevalence of high-risk HPV (human papillomavirus) and genetic alterations in nonmalignant tonsils.

Methods: We collected benign fresh tonsillar tissue specimens from 477 patients undergoing tonsillectomy because of chronic tonsillitis or tonsillar hypertrophy in 2012 (Group A, n=237) and in 2015 (Group B, n=240). Luminex xMAP technique served to detect E6/E7 DNA from 16 different high-risk HPV types.

Chromosome instability in tumor resection margins of primary OSCC is a predictor of local recurrence.

Background: The local recurrence rate in oral squamous cell cancer (OSCC) hardly decreases. This is partly due to the presence of (pre)malignant cells in the remaining tissue after resection, that may lead to the development of a new tumor in time. Detection of histologically (pre)malignant cells in the tumor resection margins should predict these patients at risk for recurrence, however this appears to be difficult in routine practice.

Chromosome instability predicts progression of premalignant lesions of the larynx.

The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7.

Comprehensive analysis of HPV16 integration in OSCC reveals no significant impact of physical status on viral oncogene and virally disrupted human gene expression.

Infection with high-risk human papillomavirus (HPV) type 16 is an independent risk factor for the development of oropharyngeal squamous cell carcinomas (OSCC). However, it is unclear whether viral integration is an essential hallmark in the carcinogenic process of OSCC and whether HPV integration correlates with the level of viral gene transcription and influences the expression of disrupted host genes. We analyzed 75 patients with OSCC.

P16(INK4A) immunostaining is a strong indicator for high-risk-HPV-associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low-risk-HPV-infection in head and neck papillomas and laryngeal dysplasias.

Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16(INK4A) is often used as a surrogate marker for HPV-infection, although there is still controversy with respect its reliability. Our aim was to determine if p16(INK4A) overexpression can accurately predict both high-risk and low-risk-HPV-presence in (pre)malignant and benign head and neck lesions.

Human papillomavirus multiplex ligation-dependent probe amplification assay for the assessment of viral load, integration, and gain of telomerase-related genes in cervical malignancies.

We evaluated the reliability of a novel multiplex ligation-dependent probe amplification (MLPA) assay in detecting integration of human papillomavirus (HPV) based on the viral E2/E6 copy number ratio in formalin-fixed and paraffin-embedded cervical lesions. The MLPA results were compared with those of amplification of papillomavirus oncogene transcripts for RNA, detection of integrated papillomavirus sequences for DNA, and HPV fluorescence in situ hybridization (FISH). DNA was isolated from 41 formalin-fixed and paraffin-embedded HPV-positive cervical lesions (cervical intraepithelial neoplasia grade 3 lesions, squamous cell carcinomas, and adenocarcinomas) for MLPA analysis.

CD44 and OTP are strong prognostic markers for pulmonary carcinoids.

Purpose: Pulmonary carcinoids are well-differentiated neuroendocrine tumors showing usually a favorable prognosis. However, there is a risk for late recurrence and/or distant metastasis. Because histologic classification in typical and atypical carcinoids is difficult and its reliability to predict disease outcome varies, we evaluated three genes as potential prognostic markers, that is, orthopedia homeobox (OTP), CD44, and rearranged during transfection (RET).

p16 INK4A overexpression is frequently detected in tumour-free tonsil tissue without association with HPV.

Aims: Oncogenic human papillomavirus (HPV) type 16 has been strongly associated with tonsillar squamous cell carcinoma (TSCC) and appears to be of prognostic significance. Because HPV+ TSCC also accumulates p16(INK4A), this cyclin-dependent kinase inhibitor has been proposed as a potential biomarker for HPV in clinical diagnosis. The aim of this study was to determine the prevalence of HPV in tumour-free tonsillar tissue and the value of p16(INK4A) overexpression in predicting its presence.

Molecular evidence for a clonal relationship between multiple lesions in patients with unknown primary adenocarcinoma.

Unknown primary adenocarcinoma (UPA) comprises a group of heterogeneous cancers of great clinical and biological interest. UPA presents as metastatic disease without a detectable primary site after medical workup. Here we investigated whether or not a clonal relationship exists between multiple tumors within individual UPA patients.

Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas.

Oncogenic human papillomavirus (HPV) is a causative agent in a subgroup of head and neck carcinomas, particularly tonsillar squamous cell carcinomas (TSCC). This study was undertaken because controversial data exist on the physical status of HPV-DNA and the use of p16(INK4A) overexpression as surrogate HPV marker, and to examine the impact of HPV and tobacco consumption on the clinical course of TSCC. Tissue sections of 81 TSCC were analyzed by HPV 16-specific fluorescence in situ hybridization (FISH) and p16(INK4A)-specific immunohistochemistry.

A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen.

Human papillomavirus type 16 (HPV16) plays a role in the development of a subgroup of head and neck squamous cell carcinomas (HNSCC). However, uncertainty exists about the true impact of HPV in this tumor type as conflicting reports have been published with prevalence rates from 0 to 100%. We aimed to find a detection algorithm of a biologically and thus clinically meaningful infection, applicable for high-throughput screening of frozen and formalin-fixed paraffin embedded (FFPE) specimens.

A subset of head and neck squamous cell carcinomas exhibits integration of HPV 16/18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in p53 exons 5-8.

Besides well-known risk factors such as tobacco use and alcohol consumption, oncogenic human papillomavirus (HPV) infection also has recently been suggested to promote head and neck tumorigenesis. HPV is known to cause cancer by inactivation of cell cycle regulators p53 and pRb via expression of viral oncoproteins E6 and E7. This indicates that p53 mutations are not a prerequisite in HPV-induced tumor development.

Morphologically normal, CD30-negative B-lymphocytes with chromosome aberrations in classical Hodgkin's disease: the progenitor cell of the malignant clone?

A recent study observed that numerical chromosome abnormalities in Hodgkin's disease (HD) are detected not only in morphologically abnormal Hodgkin/Reed-Sternberg cells, but also in a fraction of morphologically normal cells. However, the phenotypic constitution of these genetically abnormal, morphologically normal cells and their relationship to the malignant Hodgkin/Reed-Sternberg cells could not be established in the earlier cases studied, because of the low frequency of these cells. The present study investigated two cases of classical Hodgkin's disease containing a relatively large population of such apparently normal cells with aberrant chromosome copy numbers.

Chromosomal abnormalities in Hodgkin's disease are not restricted to Hodgkin/Reed-Sternberg cells.

Hodgkin and Reed-Sternberg cells are considered to represent the malignant fraction in Hodgkin's disease. Several studies have shown that the Hodgkin and Reed-Sternberg cells are chromosomally abnormal, but genetic data about the morphologically normal cell population in Hodgkin's disease are very limited. This latter cell population has therefore been examined for chromosomal aberrations, using the in situ hybridization (ISH) procedure, making use of DNA probes for chromosomes 1, 7, 8, 9, 11, 12, 15, 17, and 18.

Large-cell anaplastic non-Hodgkin's lymphoma originating in donor cells after allogenic bone marrow transplantation.

Second neoplasms after allogenic bone marrow transplantation (BMT) occur in donor cells; however, host origin generally cannot be excluded. Using fluorescence in situ hybridization (FISH) the origin of the malignant population can be proven indisputably. In a female patient with CD30+ large-cell anaplastic non-Hodgkin's lymphoma (LCAL) after BMT with an HLA-identical brother donor, FISH using anti-CD30 immunocytochemistry in combination with anti-Y- and anti-EBV RNA probes was applied.