Expression of EphB4 in head and neck squamous cell carcinoma

EphB4 is a receptor tyrosine kinase that is expressed on epithelial cells during fetal life. It is also expressed on some venous endothelial cells. We conducted a study of six men with primary squamous cell carcinoma of the head and neck (HNSCC) that had metastasized to the cervical lymph nodes. Our goal was to determine if EphB4 is aberrantly expressed in cases of HNSCC and to determine if there is a qualitative difference between the expression of EphB4 on primary and metastatic tumors and its expression on normal mucosa adjacent to primary tumors. From each patient, we obtained specimens of the primary tumor, the nodal metastasis, and the adjacent normal mucosa, and we performed immunocytochemistry on each. We observed EphB4 expression in all primary and metastatic tumors and no expression in the normal tissue. In each of the six patients, expression was greater in the metastatic tumor than in the primary tumor. We conclude that EphB4 is a novel target in the treatment of HNSCC.     

Predictive factors for diagnosis of advanced-stage squamous cell carcinoma of the head and neck

OBJECTIVE: To identify the predictive factors (with emphasis on diagnostic delay) associated with the diagnosis of an advanced-clinical stage head and neck cancer. DESIGN: Cross-sectional study of patients with head and neck cancer originally recruited for a case-control study. SETTING: Three referral oncological centers in metropolitan areas in southern Brazil: S?o Paulo, Curitiba, and Goiania. PATIENTS: The study population comprised 679 patients recently diagnosed as having a previously untreated head and neck squamous cell carcinoma. MAIN OUTCOME MEASURE: Diagnosis of advanced disease (clinical stage III-IV) head and neck cancer. RESULTS: Patients with laryngeal and hypopharyngeal cancers were more likely to be diagnosed as having advanced disease than those with lip, oral, and oropharyngeal cancers (88.0% vs 74.6%) (P<.001). Patient delay was inversely associated with clinical stage at diagnosis in patients with the same cancers, while professional delay was directly associated with a higher risk of advanced clinical stage at diagnosis (P =.001 and P =.006, respectively). In the analysis of laryngeal and hypopharyngeal cancer, both patient and professional delays were associated with advanced disease, with patient delay being a stronger predictive factor than professional delay. CONCLUSIONS: Clinical stage at diagnosis was associated with sociodemographic characteristics, patient delay, and professional delay. Our results indicate that continued educational programs for the population and health care professionals regarding the identification of early symptoms of head and neck cancers are warranted.     

Racial disparities in patients with head and neck squamous cell carcinoma

OBJECTIVES/HYPOTHESIS: Black patients are reported to have a higher incidence of advanced disease and increased mortality from head and neck squamous cell carcinoma (HNSCC) but constitute the minority of patients in large-scale studies investigating the effect of race on outcome. This study sought to determine if racial disparities exist between black and white patients with HNSCC treated at a single large institution in the South with a high proportion of black patients. STUDY DESIGN: The authors conducted a nonrandomized retrospective cohort analysis. METHODS: The tumor registry was used to identify patients diagnosed with HNSCC from 1985 to 2002. The medical records of non-Hispanic white and black adult patients were retrospectively reviewed. Median household income, percentage of population below poverty level, and education level based on census tract and block information were obtained from U.S. Census 2000 data. Standard statistical analysis, including Kaplan-Meier survival curve analysis and Cox proportional hazards models, was used to analyze the effects of covariables on survival. RESULTS: A total of 1,128 patients met study criteria (478 black, 650 white). Compared with white patients, black patients were significantly younger (mean age, 53.9 vs. 56.4 years, P<.0001), male (81.2% vs. 72.3%, P=.0005), more commonly abused alcohol (88.0% vs. 74.3%, P<.0001), and were significantly less likely to have insurance (8.6% vs. 21.7%, P<.0001). There was no difference in the incidence of tobacco use (91.7%), advanced comorbidity (35.9%), or primary tumor site. Black patients had a significantly greater incidence of stage IV disease (65.7% vs. 46.6%, P<.0001) and nonoperative treatment (48.7% vs. 30.8%, P<.0001), which was performed for inoperable disease in 57.1% of black compared with 31.0% of white patients (P<.0001). Black patients resided in census block groups with significantly lower mean education level, median income, and a higher percentage of population below poverty compared with white patients. The 5-year disease-specific survival differed significantly between black (29.3%) and white (54.7%) patients (P<.0001). Cox proportional hazards models revealed that alcohol abuse, advanced TNM stage, high tumor grade, nodal disease, extracapsular spread, advanced comorbidity, and regional or distant metastatic disease were associated with poorer survival for all patients. An interaction with race was found for insurance status, nonoperative treatment, and extracapsular spread. Stepwise variable selection adjusting for patient, tumor, and treatment characteristics showed a significant effect only for race by payor status on disease-specific survival (P=.0228). CONCLUSIONS: Insurance status, treatment, and extracapsular spread differentially affected the survival of black patients compared with white patients. Only insurance status had a significant effect on survival in black patients after controlling for other variables. These data suggest that racial differences in HNSCC outcomes are primarily related to differences in access to health care.     

The cause of death in patients with head and neck squamous cell carcinoma

For patients with head and neck squamous cell carcinoma the cause of death is not well described in world literature. We report data on 106 patients diagnosed with head and neck squamous cell carcinoma who subsequently died. The literature related to this topic is discussed, and recommendations are made for data collection.     

Incidental association of thyroid carcinoma and squamous cell carcinoma of head and neck

PURPOSE: This study was carried out to address the dilemma of managing incidentally associated squamous cell carcinoma of the head and neck and thyroid carcinoma. MATERIALS AND METHODS: The patient group consists of 229 consecutive cases of squamous cell carcinoma of the head and neck and who were treated surgically at the Uludag University School of Medicine Department of Otolaryngology over a four-year period between 1997 and 2000. RESULTS: Among these patients, 3 had additional thyroid papillary carcinoma metastases (1.3%, 3/229) within the surgical specimens of the surgical procedures performed for squamous cell carcinoma of the head and neck. Complementary thyroidectomy was recommended but could not be performed in one of three cases because of the patient's refusal, and the primary focus of thyroid carcinoma could be found in only one of these two cases who had undergone complementary thyroidectomy. All three patients received postoperative radioactive iodine and thyroid hormone suppression, and all are free of disease after 49, 46, and 19 months of follow-up, respectively. CONCLUSIONS: Management of thyroid carcinoma found incidentally during treatment of squamous cell carcinoma of the head and neck is still debatable, and all patients must be evaluated individually with regard to its benefit. Our limited experience suggests that total thyroidectomy may not be regarded as mandatory in managing these patients.     

p53 codon 72 polymorphism association with head and neck squamous cell carcinoma

p53 tumoral suppressor gene harbors a functional polymorphism which codes either arginine (Arg) or proline (Pro) in the protein p53 of codon 72. Such polymorphism has been associated with the development or prognosis of head and neck squamous cell carcinoma (HNSCC).Aim: we assessed codon 72 p53 allelic frequencies and genotypes in HNSCC Iranian patients.Study design: Case Study.Materials and Methods: a total of 132 HNSCC patients and 123 healthy controls were genotyped. DNA source was from mononuclear cells of the peripheral blood. DNA amplification was done by means of the allele-specific polymerase chain reaction.Results: genotypes and allele distribution were not significantly different between patients and controls. Moreover, no statistically significant association was found between the 72 and p53 codon tumor location, gender or age at the time of diagnosis. However, the Pro/Pro genotype was significantly increase in stage IV patients (30.8%) when compared to stages I-III of the disease (11.1%) (p=0.03), and a significantly higher percentage of patients with the Pro allele had and a risk increase in stage IV disease (OR=2.2, 95% CI=1.2-4.2, p=0.01).Conclusion: data revealed that the p53 polymorphism do not impact the risk of HNSCC in Iranians, nonetheless, it can affect tumor progression to a higher tumor stage.     

Whole-body MRI for staging patients with head and neck squamous cell carcinoma

Conclusions. Whole-body MRI is feasible for the tumor staging of patients with malignant head and neck tumors and appears to be a quick, reliable and proven alternative in general and for patients with contraindications to CT. This examination minimizes the logistical effort required compared to multimodality strategies. Its economic impact remains to be determined. Objective. To assess the performance of whole-body MRI for staging patients with squamous cell carcinoma of the head and neck region. Material and methods. This was a randomized, prospective clinical study. For tumor staging, 21 patients (mean age 56.7 years; range 43–80 years) with advanced malignant head and neck tumors underwent whole-body MRI in addition to routinely performed imaging investigations, including sonography, chest X-ray, CT of the head, neck and thorax and endoscopy. All investigations were accomplished within a period of 10±3 days in a random order. A randomized, blinded, consensus assessment of all the whole-body MRI examinations was performed by two radiologists. The localization and extent of the primary tumor and metastases were documented for whole-body MRI and compared to the standard of reference (all other imaging modalities as well as histology). Point estimates of the diagnostic accuracy of whole-body MRI were calculated. Results. In accordance with the standard of reference, the overall TNM category was correctly determined with whole-body MRI in all 21 patients. However, four patients were classified as having carcinoma of unknown primary, as the primary tumor was not found with any imaging modality. Two patients had mediastinal, pulmonary and hepatic metastases.     

Angiogenesis in head and neck squamous cell carcinoma

Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Research into this process not only offers new insights into tumour biology but is also leading to the development of realistic novel and minimally toxic anti-tumour therapies. Various pro-angiogenic and anti-angiogenic cytokines and pathways have been characterized and their interrelationships are becoming increasingly complex as new findings are made. This article reviews the current understanding of tumour angiogenesis, the basic mechanisms involved and the more important and investigated pathways and proteins involved.     

Hyercalcaemia in head and neck squamous cell carcinoma

PURPOSE OF REVIEW: Patients with advanced head and neck cancer are being treated with chemo-radiotherapy, and life is being prolonged, with or without persistent disease, for longer than was previously. Hypercalcaemia may present in patients with advanced or disseminated head and neck cancer, and, as such, these patients may present to a larger variety of clinicians for advice concerning their symptoms and illness. Modes of presentation of hypercalcaemia and treatment strategies are reviewed. RECENT FINDINGS: There were previously few large series of head and neck cancer patients diagnosed with hypercalcaemia, which may or may not have been related to their cancer being treated. Investigations, by way of blood/serum calcium level, may identify such patients. Patients with cancer-related hypercalcaemia have a poor prognosis, but many may respond temporarily to treatment when offered, with an improvement of their quality of life and death. SUMMARY: Hypercalcaemia should and must be considered in all patients who have or possibly have a diagnosis of a head and neck cancer and who present unwell with symptoms of fatigue, lethargy and somnolence. Investigation must include serum calcium (corrected for serum albumin binding) and parathyroid hormone level. Patients may be treated by a combination of rehydration and bisulphonate therapy until the serum calcium is reduced to a level below 3 mmol/l. The majority of patients diagnosed with hypercalcaemia due to head and neck malignancy die of their diseases in the short term, but some may enjoy a prolongation of life with reasonable quality if diagnosed and treated aggressively.     

Whole-body MRI for staging patients with head and neck squamous cell carcinoma

CONCLUSIONS: Whole-body MRI is feasible for the tumor staging of patients with malignant head and neck tumors and appears to be a quick, reliable and proven alternative in general and for patients with contraindications to CT. This examination minimizes the logistical effort required compared to multimodality strategies. Its economic impact remains to be determined. OBJECTIVE: To assess the performance of whole-body MRI for staging patients with squamous cell carcinoma of the head and neck region. MATERIAL AND METHODS: This was a randomized, prospective clinical study. For tumor staging, 21 patients (mean age 56.7 years; range 43-80 years) with advanced malignant head and neck tumors underwent whole-body MRI in addition to routinely performed imaging investigations, including sonography, chest X-ray, CT of the head, neck and thorax and endoscopy. All investigations were accomplished within a period of 10+/-3 days in a random order. A randomized, blinded, consensus assessment of all the whole-body MRI examinations was performed by two radiologists. The localization and extent of the primary tumor and metastases were documented for whole-body MRI and compared to the standard of reference (all other imaging modalities as well as histology). Point estimates of the diagnostic accuracy of whole-body MRI were calculated. RESULTS: In accordance with the standard of reference, the overall TNM category was correctly determined with whole-body MRI in all 21 patients. However, four patients were classified as having carcinoma of unknown primary, as the primary tumor was not found with any imaging modality. Two patients had mediastinal, pulmonary and hepatic metastases.     

Cytokeratin 18 expression in squamous cell carcinoma of the head and neck

Cytokeratin (CK) expression was studied in squamous cell carcinomas of different subsites in the head and neck by using cryostat sections from 27 head and neck squamous cell carcinomas (HNSCCs) and 6 cell lines established from HNSCC. All tissues were analyzed immunohistochemically with a panel of monospecific anti-keratin monoclonal antibodies. Most carcinomas recapitulated the expression pattern of keratins present in the basal layer of normal epithelium from the site of tumor origin. Regional differences in the expression of simple-epithelial type of keratins in stratified (pseudostratified) epithelia were to a large extent repeated in corresponding carcinomas. In the present study, localization of various keratins were surveyed and CK 18 specific monoclonal antibodies were specifically used to distinguish SCCs of the larynx or hypopharynx from SCCs of the oral cavity. CK 18 staining of almost all tumor cells was detected in 11 of 12 SCCs of the larynx and hypopharynx, but was only detected sporadically in 3 of 9 SCCs of the oral cavity. The present results show that CK 18 typing might be useful for distinguishing sites of origin of various HNSCCs. Findings also indicate that CK 18 expression in SCC might be modulated by microenvironmental factors.     

Immunohistochemistry study of EGFR expression in head and neck squamous cell carcinoma

EGFR is an important transmembrane receptor member of the family of tyrosine kinases, that translates signals from both outside and inside the cell and plays a key role in numerous proceses that affect tumour development, growth, progresion, differentiation, inhibition of apoptosis and metastasis. Immunohistochemistry studies have shown that 40-80% of head and neck squamous cell carcinomas express EGFR and it has been suggested as a potential independent prognostic parameter. The objective of this study is to evaluate by immunohistochemistry the expresi6n of EGFR in a series of Head and Neck Squamous Cell Carcinoma and correlate it to clinico-pathological features and prognostic significance. We investigated expression of EGFR in 44 samples. There was a high expression in 41% of the cases. Even if we have not found that the expression of EGFR correlated with the prognosis of these patients the presence of EGFR is very important because there are chemical agents or drugs that can inhibit its activity.     

Adenosine-mediated immunosuppression in patients with squamous cell carcinoma of the head and neck

This review article describes the potential role of ectonucleotidase activity, adenosine metabolism, and the adenosinergic signaling pathway in the suppression of the host immune system in patients with head and neck cancer. Identifying such mechanisms leads to a better understanding of immunosuppressive mechanisms in this patient population. Further, potential targets for immunotherapy in an adjuvant approach to treating squamous cell carcinoma of the head and neck in the future might be identified and improve the prognosis of these patients.     

Epigenetic events of disease progression in head and neck squamous cell carcinoma

OBJECTIVE: To examine the promoter methylation status of the 22 cancer genes and their contribution to disease progression in 6 head and neck squamous cell carcinoma (HNSCC) cell lines. DESIGN: A panel of 41 gene probes, designed to interrogate 35 unique genes with known associations to cancer including HNSCC, was interrogated for alterations in gene copy number and aberrant methylation status (22 genes) using the methylation-specific multiplex ligation-dependent probe amplification assay. SUBJECTS: Primary (A) and recurrent or metastatic (B) HNSCC cell lines UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B are described. RESULTS: Nine genes, TIMP3, APC, KLK10, TP73, CDH13, IGSF4, FHIT, ESR1, and DAPK1, were aberrantly methylated. The most frequently hypermethylated genes were APC and IGSF4, observed in 3 of 6 cell lines, and TP73 and DAPK1, observed in 2 of 6. For KLK10 and IGSF4, TIMP3 and FHIT, and TP73, in UMSCC-11B, UMSCC-17B, and UMSCC-81B, respectively, promoter hypermethylation was a disease progression event, indicating complete abrogation of tumor suppressor function for KLK10, IGSF4, and TIMP3 and gene silencing of 1 of 2 copies of TP73. Hypermethylation of IGSF4, TP73, CDH13, ESR1, DAPK1, and APC were primary events in UMSCC-17A. CONCLUSIONS: Gene silencing through promoter hypermethylation was observed in 5 of 6 cell lines and contributed to primary and progressive events in HNSCC. In addition to genetic alterations of gains and losses, epigenetic events appear to further undermine a destabilized genomic repertoire in HNSCC.     

High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia

BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by a high degree of genomic instability and predisposition to cancer development. Recent evidence suggests that the incidence of head and neck squamous cell carcinoma (HNSCC) may be increased in patients with FA. OBJECTIVE: To determine the cumulative incidence, tumor distribution, and outcome of HNSCC in patients with FA. DESIGN AND SETTING: We analyzed data from 754 subjects from the International Fanconi Anemia Registry, a prospectively collected database of patients with FA. MAIN OUTCOME MEASURES: Cumulative incidence of HNSCC and 2-year overall, relapse-free and disease-specific survival. RESULTS: Of the 754 patients in the International Fanconi Anemia Registry, 19 (3%) had HNSCC. This is a significantly higher incidence of HNSCC compared with that observed in the general population (standardized incidence ratio, 500; 95% confidence interval, 300-781) (P<.001). The patients' age ranged from 15 to 49 years (median, 31 years), and there was a 2:1 female predominance. Surgical treatment was well tolerated (n = 17); however, radiation therapy and chemotherapy were associated with significant morbidity and mortality. Of the 19 patients, 10 (53%) developed locoregional recurrences within a median of 16 months from diagnosis. The median follow-up was 29 months. The 2-year disease-specific, overall, and relapse-free survival rates were 49%, 49%, and 42%, respectively. The cumulative incidence of relapse by the age of 40 years was 50%. CONCLUSIONS: In patients with FA, there is a high incidence of aggressive HNSCC at a young age. Surgery remains the mainstay of treatment because patients with FA tolerate radiation therapy and chemotherapy poorly, with significant morbidity. An increased understanding of FA-associated malignancies is not only important in the clinical management of patients with FA but can also elucidate the role of chromosomal instability in the development of HNSCC in general.