Dental caries and head and neck cancers.

Importance: Dental caries is the demineralization of tooth structures by lactic acid from fermentation of carbohydrates by commensal gram-positive bacteria. Cariogenic bacteria have been shown to elicit a potent Th1 cytokine polarization and a cell-mediated immune response.

Objective: To test the association between dental caries and head and neck squamous cell carcinoma (HNSCC).

Human papillomavirus and tobacco use in tongue base cancers.

Human papillomavirus 16 (HPV-16) infection and tobacco use are associated with human oropharyngeal cancers. We conducted a study of the role of HPV and tobacco use in base of the tongue (BOT) cancers. DNA from 34 such cancers was subjected to HPV-16 and HPV-18-specific polymerase chain reaction analysis.

Local inflammation and human papillomavirus status of head and neck cancers.

Objective: To determine whether periodontitis is associated with human papillomavirus (HPV) status of head and neck squamous cell carcinoma (HNSCC).

Design And Setting: Hospital-based case-control study in a comprehensive cancer center.

Patients: Evaluation included all patients diagnosed with incident primary squamous cell carcinoma of the oral cavity, oropharynx, and larynx between 1999 and 2007 for whom tissue samples and dental records were available (N = 124).

Genomic instability measured by inter-(simple sequence repeat) PCR and high-resolution microsatellite instability are prognostic of colorectal carcinoma survival after surgical resection.

Background: During the multiyear progression to colorectal cancer, numerous genomic alterations arise in events ranging from single base mutations to gains or losses of entire chromosomes. A single genetic change might not stand out as an independent predictor of outcome. The goal of this study was to determine if more comprehensive measurements of genomic instability provide clinically relevant prognostic information.

Chronic periodontitis-human papillomavirus synergy in base of tongue cancers.

Objective: To assess whether chronic periodontitis history predicts human papillomavirus (HPV) status in patients with base of tongue cancers.

Design: Case-control study using existing patient data.

Setting: Roswell Park Cancer Institute.

Uniparentalism in sporadic colorectal cancer is independent of imprint status, and coordinate for chromosomes 14 and 18.

Our previous allelotyping studies of 59 sporadic colorectal cancers revealed that loss of heterozygosity is most frequent for regions of chromosomes 14 and 18. Yet subsequent BAC microarray comparative genomic hybridization studies of the same tumor DNAs showed no corresponding pattern of copy number alteration for chromosome 14. To clarify this apparent discrepancy, we utilized hybridization to SNP microarrays; this revealed frequent uniparentalism for chromosome 14 and for chromosome 18.

Family cancer syndromes: inherited deficiencies in systems for the maintenance of genomic integrity.

Familial cancer syndromes have revealed important fundamental features regarding how all cancers arise through destabilization of the genome, such that somatic evolution can select for the disruption of critical cellular coordinating and regulatory features. The authors examine those cellular genes and systems whose normal role is to preserve genomic integrity and relate them to the genetic foundations of heritable cancers. By examining how these cellular systems normally function, how family cancer genes are able to affect the process of tumor progression can be learned.

Colorectal cancers in patients with the (9A/6A) polymorphism of TGFBR1 exhibit lesser inter-(simple sequence repeat) PCR genomic instability and present clinically at greater age.

TGFbeta is involved in the response to DNA damage and signaling the cell cycle checkpoint response, in large part achieved by modulating the activity of the ATM kinase. We have investigated if the presence of a common polymorphism in the TGFbeta receptor TGFBR1 might impact genomic instability in human colorectal cancer. In order to obtain statistically significant numbers of patients with the lesser polymorphism, 177 colorectal cancer patients were genotyped for either the major form of the TGFBR1 receptor gene, homozygous for an internal segment of 9 alanines (9A/9A), or the lesser form, heterozygous for the polymorphism containing 6 alanines (9A/6A).

Analysis of inter-(simple sequence repeat) PCR products from human colorectal cancers.

Genomic instability is a fundamental characteristic of solid tumors, and understanding genomic instability should significantly clarify the process of tumorigenesis. We adapted the sampling technique of inter-(simple sequence repeat) PCR [inter-(SSR) PCR] to measure genetic alterations between simple sequence repeats in colorectal tumors. It becomes important to precisely define both normal and altered inter-(SSR) PCR products.

Comparative genomic instabilities of thyroid and colon cancers.

Objectives: To assess the forms and extent of genomic instability in thyroid cancers and colorectal neoplasms and to determine if such measurements could explain the generally excellent prognosis of thyroid malignant neoplasms compared with colon carcinoma.

Design: Tumor genome analyses. Genomic instability was measured by the following 4 methods, listed in ascending order based on the size of events detected: inter-simple sequence repeat polymerase chain reaction (ISSR-PCR), fractional allelic loss (FAL) analysis, array-based comparative genomic hybridization (aCGH), and spectral karyotyping (SKY).

Allelic losses at genomic instability-associated loci in villous adenomas and adjacent colorectal cancers.

Allelic imbalances in premalignant villous adenomas were compared with those in adjacent microdissected colorectal carcinoma that had arisen directly from the adenomas. Carcinoma-adenoma pairs were examined from 17 patients who underwent resections for colorectal cancer. In all, 28 microsatellite markers were examined, from regions of the genome where individual allelic losses have been associated with overall genomic instability in colorectal carcinomas.

aCGH local copy number aberrations associated with overall copy number genomic instability in colorectal cancer: coordinate involvement of the regions including BCR and ABL.

In order to identify small regions of the genome whose specific copy number alteration is associated with high genomic instability in the form of overall genome-wide copy number aberrations, we have analyzed array-based comparative genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy number changes of a small number of specific regions were significantly correlated with elevated overall amplifications and deletions scattered throughout the entire genome. One significant region at 9q34 includes the c-ABL gene.

Genomic profiles of colorectal cancers differ based on patient smoking status.

Human sporadic colorectal cancer is the result of a lengthy somatic evolutionary process facilitated by various forms of genomic instability. Such instability arises endogenously from mutations in genes whose role is to preserve genomic integrity, and exogenously from environmental agents that generate genomic damage. We have found that cigarette smoking shifts the genomic profiles and genomic instability patterns of colorectal carcinomas.

Genomic instability of human aberrant crypt foci measured by inter-(simple sequence repeat) PCR and array-CGH.

Aberrant crypt foci (ACF) are the earliest identifiable neoplastic lesions in the colon. Thirty-two ACFs were examined for genomic instability in forms detectable either by inter-(simple sequence repeat) PCR or by array comparative genomic hybridization [array-CGH]. One-fourth of ACFs revealed moderate instability by inter-(simple sequence repeat) PCR; none showed amplifications or deletions on array-CGH.

Aberrant crypt foci.

Colon cancer evolves through epithelial cell deregulation and inappropriate proliferation. These histopathological characteristics are exemplified in the biochemical, immunohistochemical, genetic and epigenetic elements detected within colonic mucosa. Early detection is paramount for the prevention of colon cancer deaths.

Genomic instability in invasive breast carcinoma measured by inter-Simple Sequence Repeat PCR.

We have measured genomic instability in invasive breast carcinomas and assessed the relationship of genomic instability to known tumor prognostic factors. DNAs from tumors and adjacent normal tissue of 18 breast cancer patients were subjected to inter-Simple Sequence Repeat (inter-SSR) PCR for quantitation of tumor genomic instability. Associations between genomic instability level and known breast cancer prognostic factors were evaluated using the Pearson Product Moment Correlation, the Kruskal-Wallis test of independent samples and the Mann-Whitney non-parametric test.

Molecular prognosticators and genomic instability in papillary thyroid cancer.

Objectives/hypothesis: Tumor progression has been attributed to the accumulation of DNA damage concurrent with selection of advantageous mutations; this DNA damage may result from failure to maintain genomic integrity or from susceptibility to carcinogens. Glutathione S-transferases (GSTs), enzymes that metabolize many carcinogens, may play a role in preserving genome integrity. The objectives of this study are to assess the relationship of GST genotypes with prognosis, clinicopathologic parameters, and genomic instability in papillary thyroid cancer.

Tissue eosinophilic infiltration: a useful marker for assessing stromal invasion, survival and locoregional recurrence in head and neck squamous neoplasia.

Unlabelled: The assessment of stromal invasion in aerodigestive neoplastic squamous proliferation often poses diagnostic and therapeutic challenges. Eosinophilic infiltration is thought to be an adjunctive histologic criterion in determining tumor aggressiveness and invasion. We investigated whether an eosinophilic infiltration in head and neck squamous cell carcinoma measured in biopsies would aid in predicting tumor invasion, response to treatment, locoregional recurrence, and survival.

Genomic heterogeneity and instability in colorectal cancer: spectral karyotyping, glutathione transferase-Ml and ras.

Genomic instability in cancer is frequently described as being either chromosomal instability or microsatellite instability, although when events within chromosomes are monitored, extensive intrachromosomal instability is also found. Spectral karyotyping was used to visualize how extensively genomic instability gives rise to intratumor genomic heterogeneity in sporadic colorectal carcinomas. Two factors were then examined which might relate to intrachromosomal instability in colorectal cancers: the presence of the glutathione transferase-Ml gene to detoxify potential carcinogens, and the presence of activated ras which has been associated with chromosomal instability when first expressed.

The role of genomic instability in the pathogenesis of squamous cell carcinoma of the head and neck.

Measurements of genomic instability, or identification of genes responsible for instability, may potentially be used as molecular markers to predict disease course and response to therapy. Other possible applications include use of genomic instability measurements, or genes, as tools to screen for primary or recurrent disease. Methodologies for detection of genetic mutations in saliva, blood, and sputum have already been described[61,62].

Papillary thyroid cancer: high inter-(simple sequence repeat) genomic instability in a typically indolent cancer.

Objectives: The object of this study is to measure genomic instability in papillary thyroid cancer and correlate these measurements with known clinical prognosticators such as patient age, tumor size, histologic subtype, and three commonly used thyroid risk assessment indices. A secondary objective of this study was to use the measurements of genomic instability to estimate the number of mutational events present in the papillary thyroid cancer genome.

Methods: Inter-simple sequence repeat polymerase chain reaction (ISSR-PCR) is a rapid and reproducible technique for quantitation of genomic instability, or the degree of genome alteration, in solid tumors.

Anaplastic transformation of thyroid cancer: review of clinical, pathologic, and molecular evidence provides new insights into disease biology and future therapy.

Background: Anaplastic thyroid cancer ranks among the most lethal of all human malignancies. Its rarity and rapidly fatal course have made it a difficult cancer to both study and treat. Unfortunately, there has been little progress in the management and control of this malignancy.

Squamous cell carcinoma of the head and neck in nonsmokers and nondrinkers: an analysis of clinicopathologic characteristics and treatment outcomes.

Background: The objective of this study was to describe the clinicopathologic manifestations of disease and outcomes of treatment among individuals without a history of smoking tobacco or consuming alcohol who develop head and neck cancer.

Methods: Of 1648 invasive head and neck cancer cases treated between 1970 and 2001 at Roswell Park Cancer Institute, 40 patients were identified as never having smoked tobacco or consumed alcohol during their lifetime. These cases were reviewed to gather data on multiple clinicopathologic variables.

Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of anaplastic transformation by means of the inter-simple sequence repeat polymerase chain reaction.

Background: In thyroid tumors, the coexistence of well- and poorly differentiated tumor types has led to the hypothesis that poorly differentiated thyroid tumors develop from well-differentiated thyroid tumors. By evaluating the genomic instability of histologically distinct but coexisting tumor foci, this study aimed to develop an improved understanding of thyroid tumorigenesis and tumor evolution.

Design: Laser capture microdissection (LCM) was carried out on archival formalin-fixed, paraffin-embedded sections from a tumor containing foci of classic papillary thyroid cancer and anaplastic thyroid cancer.