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.     

Ectonucleotidase CD39 expression in regional metastases in head and neck cancer

Introduction: CD39 is the rate-limiting enzyme in the generation of immunosuppressive adenosine and its expression and activity are significant in tumor progression. Squamous cell carcinoma of the head and neck (HNSCC) shows an overall poor prognosis due to high local recurrence rates and early metastatic spread.

Material and methods: Primary tumor specimens and lymph node specimens harvested during neck dissection of 65 patients with a diagnosis of HNSCC were subjected to immunohistochemical and H-score analysis of CD39 expression. Demographics, histopathology and subsequent outcome were analyzed.

Results: The primary cancer was squamous cell carcinoma in all patients (male/female 55:10). H-score for CD39 expression in the primary lesion and metastatic lymph nodes was significantly higher in advanced compared to early stages with no significant differences among different tumor locations. High intratumoral and intrametastatic CD39 expression was associated with an inferior patients’ overall survival at a mean follow-up of 83.4 months (6–204 months).

Conclusion: CD39 expression in HNSCC correlated positively with tumor stage and appears to predict poor prognosis. Therefore, CD39 expression in primary lesions and metastatic lymph nodes seems to identify patients at high risk in HNSCC of all tumor sites. Immunotherapeutic approaches targeting CD39 might be promising for this patient population.     

Foxp3 expression in lymph node metastases in patients with head and neck cancer

Introduction: The prevalence and activity of regulatory T cells in patients with cancer correlates with poor prognosis. These cells are characterized by their expression of Forkhead box protein-3 (Foxp3). Squamous cell carcinoma is the most prevalent type of cancer in the head and neck region with overall poor survival rates, also due to early spread of metastatic cells.

Material and methods: Primary tumor specimens as well as lymph node specimens harvested during neck dissection of 65 patients with a diagnosis of HNSCC were subjected to immunohistochemical and H-score analysis of Foxp3 expression. Demographics, diagnoses, histopathology and subsequent outcome were analyzed.

Results: The primary cancer was squamous cell carcinoma in all patients (male/female 55:10) with the following tumor locations: oral cavity n?=?16, oropharynx n?=?28, hypopharynx n?=?11 and larynx n?=?10 (Stage III n?=?18; Stage IVA n?=?45; Stage IVB n?=?2). The H-score for Foxp3 expression in the primary lesion as well as metastatic lymph nodes was significantly higher in advanced stages compared to early stages with differences among tumor locations, which were not significant. High Foxp3 expression was associated with inferior overall survival rates at a mean follow-up of 83.4 months (6–204 months)

Conclusions: Foxp3 expression in HNSCC varied from the anatomical site and correlated positively with tumor stage and was associated with poor prognosis. Therefore, Foxp3 expressions in primary lesions as well as lymphogenic metastases appear to predict high-risk HSNCC patients. Novel therapeutic approaches targeting Foxp3⁺ cells might seem promising for this patient population.     

Effect of comorbidity on quality of life and treatment selection in patients with squamous cell carcinoma of the head and neck

OBJECTIVES: Comorbidity is significantly associated with diminished survival and quality of life (QOL) after treatment of head and neck squamous cell carcinoma (HNSCC). We sought to determine whether comorbidity influenced pretreatment QOL scores and treatment selection in patients with HNSCC. METHODS: The medical records of all patients diagnosed with HNSCC who participated in pretreatment QOL analysis over a 15-month period were retrospectively reviewed. Patients with a history of prior treatment for head and neck cancer, unresectable, or distant metastatic disease were excluded. The University of Washington (UW) QOL questionnaire, Performance Status Scale (PSS), and Karnofsky score were used to measure pretreatment QOL. Comorbidity was graded using the Modified Medical Comorbidity Index. RESULTS: Of 75 patients who met study criteria, 33 underwent primary surgical therapy, and 42 underwent nonoperative (radiation or chemoradiation) therapy. Treatment groups did not differ with respect to patient demographics, UW QOL scores, PSS scores, Karnofsky score, or comorbidity. Treatment groups differed significantly by disease stage and primary site. Patients with advanced stage disease (III/IV) or oropharyngeal primary tumors were more likely to undergo nonoperative treatment, compared with patients with early stage disease (I/II) or oral cavity primary tumors (P < .005). No significant association was found between comorbidity and pretreatment QOL scores. CONCLUSIONS: Comorbidity was not significantly associated with treatment selection or pretreatment QOL scores in patients with HNSCC. Location of the primary tumor and disease stage were significantly associated with treatment selection. Further studies are required to determine the effect of comorbidity on patient and tumor responses to treatment.     

CD73 expression in lymph node metastases in patients with head and neck cancer

Introduction: CD73 is an enzyme crucial in the metabolism of immunosuppressive adenosine. In cancer, it has various functions including tumor growth and metastases. Squamous cell carcinoma of the head and neck has an overall poor prognosis, also due to early spread of metastatic cells.

Materials and methods: Tumor and lymph node specimens of 65 patients with HNSCC were subjected to immunohistochemical and H-score analysis of CD73 expression. Demographics, diagnoses, histopathology and subsequent outcome were analyzed.

Results: The primary cancer was squamous cell carcinoma in all patients (male/female 55:10) with the following locations: oral cavity n:16, oropharynx n:28, hypopharynx n:11 and larynx n:10. H-score for CD73 expression in the primary lesion and metastatic lymph nodes was significantly higher in advanced compared to early stages with no significant differences among tumor locations. High CD73 expression was associated with reduced overall survival rates at a mean follow-up of 83.4 months (6–204 months).

Conclusions: CD73 expression in HNSCC correlated positively with tumor stage and was associated with poor prognosis. Therefore, CD73 expression in primary lesions and regional metastases appears to predict HNSCC patients at high risk of all tumor sites. Therapeutic approaches targeting CD73 might seem promising for this patient population.     

Hemangiopericytoma of the head and neck

PURPOSE: To report a series of patients with hemangiopericytoma (HP) of the head and neck, to review pathological features of these tumors, and to discuss management options. MATERIALS AND METHODS: A retrospective review of the medical records at the University of California, Los Angeles (UCLA) Medical Center in Los Angeles, CA, was done in order to identify those patients with primary HP of the head and neck, including soft tissue and mucosal sites. RESULTS: Ten patients with HP of the head and neck were identified. There was an equal sex distribution and an average age of 36 (range 10-65). Seven of the tumors arose from soft tissue sites in the head and neck, and the remaining 3 arose from the mucosa. All patients underwent wide excision of the primary lesion with a local recurrence rate of 40%. Thirty percent of patients developed metastatic lung disease 0 to 8 years after initial diagnosis. Each patient who developed metastatic disease had abundant mitoses on pathological review compared with rare or absent mitoses in the lesions that took a more benign course. CONCLUSIONS: Pathological appearance of resected HP is predictive of later metastatic potential. Long-term follow-up is necessary in patients even after radical resection because recurrence or metastasis may be delayed by many years.     

乙酰肝素酶在头颈部鳞状细胞癌的表达及其临床意义

目的探讨乙酰肝素酶（heparanase，HPSE）在头颈部鳞癌的表达与临床病理特征及预后的关系。方法对62例头颈肿瘤手术切除标本进行检测，采用免疫组化技术检测HPSE在原发肿瘤组织及其淋巴转移灶中的表达，分析HPSE的表达同患者的年龄、临床分期、病理分级、有无淋巴转移及与预后的关系。结果HPSE在癌旁黏膜组织中不表达或少表达，在大多数头颈肿瘤组织中呈阳性表达，阳性表达率为69．3％（43／62），主要为胞质表达。HPSE的表达在患者的年龄、肿瘤的病理分级方面比较，差异无统计学意义（Х^2=0．05，Х^2=3．84，P值均〉0．05）；而在有无淋巴转移以及肿瘤的临床分期方面差异有统计学意义（Х^2=3．98，Х^2=8．06，P值均〈0．05）；HPSE在原发灶及其淋巴转移灶中的表达之间呈明显正相关（r=0．9162，P=0．001）；Kaplan—Meier法计算，HPSE阳性组的3年累积生存率为25．9％，HPSE阴性组的3年累积生存率为72．7％，二者差异有统计学意义（Х^2=11．607，P=0．001）。HPSE的表达和肿瘤的TNM临床分期分别为影响预后的独立因素，二者分别与患者的预后显著相关（Х^2值分别为16．86和19．73，P值均〈0．05）。结论HPSE在头颈鳞癌中表达显著增高。HPSE的表达与有无淋巴转移、肿瘤的临床分期密切相关。HPSE的表达、肿瘤的临床分期是影响患者预后的独立因素。     

Multi-spectral imaging analysis of HSPB1 expression in head and neck squamous cell carcinoma

The objective of this study was to obtain more accurate quantitation of HSPB1 expression in HNSCC using a novel quantitative protein expression analysis system based on multispectral imaging. The study was a retrospective laboratory study of HNSCC patients treated at tertiary care academic medical center. Archival tissue samples from forty seven patients with HNSCC were subjected to immunohistochemistry using primary antibody to HSPB1. Seven of the patients had early stage cancers (TNM stage I/II) and forty patients had advanced stage cancers (TNM stage III/IV). HSPB1 expression was increased in advanced stage versus early stage cancers. Further investigation of HSPB1 as a potential biomarker for HNSCC is warranted.     

鼻咽癌中EphB4、EphrinB2的表达及临床意义

目的研究促红细胞生成素诱导的肝细胞受体EphB4及其配体EphrinB2在鼻咽癌组织中的表达情况及其与各临床病理因素之间的关系。方法应用免疫组化SP法检测136例鼻咽癌组织标本及20例鼻咽黏膜慢性炎症组织中EphB4和EphrinB2的表达情况。结果136例鼻咽癌组织中EphB4、EphrinB2的阳性表达率分别为65．4％和63．2％,二者的阳性表达均明显高于鼻咽黏膜慢性炎组织：EphB4gnEphrinB2蛋白的阳性表达分别与淋巴结转移、颅神经麻痹、颅底侵犯、临床分期相关,而与性别、年龄、病理类型、茎突前、后间隙侵犯均无显著相关性;EphB4与EphrinB2蛋白的表达显著相关。结论EphB4、EphrinB2可能在鼻咽癌的浸润、转移和血管生成中起着重要作用,它们有望成为判断鼻咽癌发生、发展、预后及指导治疗的新的生物学指标。     

Expression of VEGF, HGF, IL-6, IL-8, MMP-9, Telomerase in Peripheral Blood of Patients with Head and Neck Squamous Cell Carcinoma

Objectives

This study investigated the telomerase expression in peripheral blood mononuclear cells (PBMCs) and the relationship between the serum level of several soluble factors such as vascular endothelial growth factor (VEGF), hepatocyte growth factor, interleukin (IL)-6, IL-8, and matrix metallopeptidase-9 and the clinicopathological features of patients with head and neck squamous cell carcinoma (HNSCC).

Methods

Peripheral blood samples were collected from 50 HNSCC patients and 15 normal controls. The telomerase activity in the PBMCs was measured by Telomere Repeat Amplification Protocols. The serum levels of the soluble factors were analyzed by enzyme-linked immunosorbent assay.

Results

The expression of telomerase in the PBMCs of HNSCC patients was significantly correlated with the N and American Joint Committee on Cancer (AJCC) stages. The serum VEGF level was significantly higher in the patients with an advanced T stage, N stage and AJCC stage. Serum VEGF was significantly related with the expression of telomerase in the PBMCs. The telomerase expression and the VEGF expression were shown to be independent factors associated with poor survival.

Conclusion

The telomerase expression in the PBMCs and the serum VEGF level of HNSCC patients were significantly correlated with the N stage, the AJCC stage and the prognosis.     

Identification of distant metastases with positron-emission tomography-computed tomography in patients with previously untreated head and neck cancer

OBJECTIVES: To investigate the utility of positron-emission tomography-computed tomography (PET-CT) in identifying distant metastatic disease in patients with previously untreated head and neck squamous cell cancer (HNSCC) prior to definitive treatment. MATERIALS AND METHODS: Retrospective analysis of 27 consecutive patients with previously untreated HNSCC who underwent PET-CT imaging in addition to chest radiography (CXR) as part of their metastatic workup. RESULTS: The majority of patients (89%) had TNM stage III or IV disease. PET-CT was suspicious for pulmonary malignancy in four (15%) patients and indeterminate in one (4%) patient. CXR was suspicious for pulmonary malignancy in two (7%) patients. Pulmonary metastases or a new lung primary was present in 3 (11%) patients: 3 of 4 (75%) patients with positive PET-CT scans and 0 of 23 (0%) patients with negative or indeterminate PET-CT scans compared with 2 of 2 (100%) patients with positive CXR and 1 of 25 (4%) patients with negative CXR. The sensitivity and specificity of PET-CT in predicting pulmonary malignancy was 100% and 96%, respectively, with a positive predictive value of 75% and a negative predictive value of 100%. The sensitivity and specificity of CXR in predicting pulmonary malignancy was 67% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 96%. Including nonpulmonary sites, the overall incidence of distant metastatic disease was 19% (5/27) with 11% (3/27) unsuspected prior to PET-CT. CONCLUSIONS: PET-CT improves detection of metastatic disease in the high-risk patient and should be performed as part of the routine pretreatment evaluation of patients with advanced stage HNSCC.     

Deferring planned neck dissection following chemoradiation for stage IV head and neck cancer: the utility of PET-CT

OBJECTIVE: To determine whether combined positron emission tomography and computed tomography (PET-CT) may be of value in deferring planned neck dissections for patients with advanced head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Observational study of patients with de novo cervical > or =N2 regional spread of HNSCC in a tertiary care academic medical center. METHODS: Forty-three patients were identified who underwent post-treatment PET-CT within 6 months of completing neoadjuvant chemotherapy combined with radiation therapy (CRT). The PET-CT was "positive" if the radiologist recommended tissue sampling or resection of cervical lymph nodes, or if there was progressive neck disease in the setting of distant metastatic disease. Patients who had positive PET-CT underwent confirmatory biopsy given clinical suspicion for regional cervical metastasis without distant disease. Patients with negative PET-CT were followed clinically and radiographically for a minimum of 5 months (median 18.1 months) after CRT. RESULTS: Ten (22%) of the 43 post-treatment PET-CT studies were positive. Seven of the 10 PET-CT scans (70% of positives) were true-positive given histologically-confirmed residual viable tumor or progressive disease including disease in the neck. The 3 remaining studies (30% of positives) were false-positive PET-CT results, given resolution of fluorodeoxyglucose (FDG) avidity on subsequent imaging or tissue sampling demonstrating absence of viable tumor cells. Of the 33 patients with negative PET-CTs in the neck, 1 patient had absence of FDG-avidity in the setting of malignant disease in the neck (3% false negatives); otherwise, patients with an initially negative PET-CT scan had no recurrences during the study (97% true negatives). This corresponds to a sensitivity of 87.5% (7/8), a specificity of 91% (32/35), a positive predictive value of 70% (7/10), a negative predictive value of 97% (32/33), and accuracy of 91% (39/43) for PET-CT scans in the detection of cervical metastatic disease after CRT. Overall, 37 (86%) of 43 patients were spared neck dissection using this technology without evidence of recurrent disease in the neck at extended follow-up. CONCLUSIONS: Our results suggest that planned neck dissection after CRT for HNSCC may be deferred in favor of serial PET-CT imaging, and that sampling of areas of suspicious FDG-avid uptake can be rationally considered prior to therapeutic neck dissection. These data also suggest that negative PET-CT scans are highly reliable for the absence of residual cervical nodal disease.     

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.     

喉癌组织中树突状细胞抑癌基因p63和金属蛋白酶组织抑制因子-1表达的意义

目的探讨树突状细胞(S-100)、抑癌基因p63、金属蛋白酶组织抑制因子-1(TIMP-1)在喉癌组织中的表达及与吸烟、饮酒、病理学分级、临床TNM分期和预后等因素的关系.方法应用组织芯片技术和免疫组织化学SP法检测85例喉鳞状细胞癌组织中 S-100、p63、TIMP-1等因子的表达 .结果85例中,6例组织芯片脱落或无肿瘤细胞.对79例进行S-100检测,其中47例(59.5%)出现阳性细胞(0～34个/视野).S-100阳性树突状细胞浸润程度与喉癌分化程度、临床分期差异均有统计学意义(均P<0.05).对79例进行TIMP-1检测,其中35例(44.3%)为阴性表达,44例(55.7%)为阳性表达.TIMP-1蛋白阳性表达与患者肿瘤临床分期、有无淋巴结转移及预后差异均有统计学意义 (均P<0.05).在79例中,58例p63表达阳性(73.4%),平均染色比率为45.5%,但未发现与临床因素相关.结论TIMP-1、S-100与肿瘤的生长、分化有关,可作为临床检测预后的重要参考指标.     

Evaluation of the primary tumour and the metastatic lymph node with or without extracapsular spread by means of argyrophillic nucleolar regions (AgNOR)

Though TNM staging is the most popular clinical system for defining the prognosis of Head and Neck Squamous Cell Carcinoma (HNSCC), different clinical trials of the tumours with the same TNM stage have caused doubts about this system. Extra Capsular Spread (ECS) in a metastatic lymph node is one of the recently defined prognostic factors in HNSCC. The hypothesis of this study was to assess the relationship between the primary tumour of laryngeal and oral cavity squamous cell carcinoma and the metastatic lymph nodes with and without ECS. The argyrophillic Nucleolar Organiser Regions (AgNOR) count was used as an index of the grade of malignancy of the neoplastic tissue. As a result, significantly higher AgNOR counts were obtained in the metastatic lymph nodes with ECS than in the primary tumours, while the lowest AgNOR counts were found in the metastatic lymph nodes without ECS. However, when primary tumours of the metastatic lymph nodes with ECS and the primary tumours of the metastatic lymph nodes without ECS were compared, no significant difference was found.     

Sentinel lymph node biopsy in head and neck squamous cell carcinoma

OBJECTIVES/HYPOTHESIS: Sentinel lymph node biopsy is a minimally invasive method to stage the regional lymphatics that has revolutionized the management of patients with intermediate-thickness cutaneous melanoma. Head and neck surgeons have been encouraged by the accuracy of sentinel lymph node biopsy in cutaneous melanoma and have applied the technique to patients with head and neck squamous cell carcinoma (HNSCC). The objectives of the study were 1) to study the feasibility and accuracy of sentinel lymph node biopsy as a method to stage the regional lymphatics in HNSCC and 2) to determine whether there are qualitative differences between the cutaneous and mucosal lymphatics that would affect the technique used in HNSCC. STUDY DESIGN: Two methods of investigation were employed: a prospective laboratory study using a feline model for sentinel lymph node biopsy and a retrospective review of patients who received lymphoscintigraphy before neck dissection and intraoperative identification of the sentinel lymph node. METHODS: Lymphoscintigraphy and a gamma probe were used in four felines to study the kinetics of technetium-labeled sulfa colloid (Tc-SC) in the mucosal lymphatics. In the second part of the feline study, eight subjects were studied intraoperatively. Tc-SC and isosulfan blue dye were used to study the injection technique for the mucosal lymphatics and to determine the time course of the dye and Tc-SC to the sentinel lymph node. In Part II of the present study, a retrospective review of 33 patients with HNSCC was conducted. Twenty patients (stage N0) whose treatment included elective neck dissection were studied with preoperative lymphoscintigraphy and underwent intraoperative identification of the sentinel lymph node to determine the accuracy and feasibility of sentinel lymph node biopsy. Eight patients with palpable neck disease and five patients with recurrent or second primary disease whose previous treatment included neck dissection were also studied with lymphoscintigraphy before neck dissection. RESULTS: In the feline study, both Tc-SC and isosulfan blue dye traversed the lymphatics rapidly, appearing in the sentinel lymph node in less than 5 minutes. Modification of the injection technique used for cutaneous melanoma was required to depict the sentinel lymph node of the base of tongue. In the human study, the sentinel lymph node was accurately identified in 19 of 20 (95%) N0 patients. On average, 2.9 sentinel lymph nodes (range, 1-5) were identified in 2.2 (range, 1-4) levels of the neck. Sentinel lymph nodes were bilateral in 4 of 19 patients. When the sentinel lymph node was identified, it accurately predicted the pathological nodal status of the regional lymphatics. Three of 20 patients had cervical metastases, and the sentinel lymph node was identified in 2 of 3 patients with pathologic nodes (pN+). Focal areas of radiotracer uptake were identified in seven of eight patients with palpable disease. These areas corresponded to the level with palpable disease in four patients. The lymphatics delineated by lymphoscintigraphy in the five patients with previous neck dissection were outside the levels that had been dissected. Lymphoscintigraphy depicted collateral patterns of lymphatic drainage. CONCLUSIONS: Sentinel lymph node biopsy is technically feasible and is a promising, minimally invasive method for staging the regional lymphatics in patients with stage N0 HNSCC. Lymphoscintigraphy alone may determine the levels that require treatment in patients with disrupted or previously operated cervical lymphatics.     

Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx

OBJECTIVE: To determine the impact of delayed regional metastases, distant metastases, and second primary tumors on the therapeutic outcomes in squamous cell carcinomas of the larynx and hypopharynx. STUDY DESIGN: Chart review and statistical analysis. METHODS: A retrospective tumor registry analysis was made of patients with squamous cell carcinomas of the larynx and hypopharynx who were treated with curative intent in the Department of Otolaryngology-Head and Neck Surgery and the Radiation Oncology Center of the Washington University School of Medicine (St. Louis, MO) between January 1971 and December 1991 and developed delayed regional metastases (2 y after treatment), distant metastases, and second primary malignancies. RESULTS: In 2550 patients, the mean age (59.8 y), sex (8.5 male patients and 1 female patient), and tumor differentiation did not affect the incidence of delayed distant, regional, or second primary malignancies. The overall incidence of delayed regional metastases was 12.4% (317/2550 patients); distant metastases, 8.5% (217/2550); and second primary tumors, 8.9% (228/2550), with a 5-year disease-specific survival of 41%, 6.4%, and 35%, respectively. Second primary malignancies were not statistically related to the origin of the primary tumor, tumor staging, or delayed regional and distant metastases (P =.98). Delayed regional metastases and distant metastases were related to advanced primary disease (T4 stage), lymph node metastases (node positive [N+]), tumor location (hypopharynx), and locoregional tumor recurrence (P < or =.028). Advanced regional metastases at initial diagnosis (N2 and N3 disease) increased the incidence of delayed and distant metastases threefold (P =.017). These two metastatic parameters were significantly greater in hypopharyngeal tumors than in laryngeal tumors (P =.037). The incidences of delayed regional metastases by anatomical location of the primary tumor were as follows: glottic, 4.4%; supraglottic, 16%; subglottic, 11.5%; aryepiglottic fold, 21.9%; pyriform sinus, 31.1%; and posterior hypopharyngeal wall, 18.5%. The incidences of distant metastases were as follows: glottic, 4%; supraglottic, 3.7%; subglottic, 14%; aryepiglottic fold, 16%; pyriform fossa, 17.2%; and posterior hypopharyngeal wall, 17.6%. Seventeen hypopharyngeal tumors (2%) presented with M1 disease. Delayed regional metastases to the ipsilateral treated neck had a significantly worse survival prognosis than delayed metastases to the contralateral nontreated neck (P =.001). CONCLUSIONS: Conclusions are as follows: 1) The incidence of second primary tumors is independent from the primary tumor staging and distant and delayed regional metastases. The highest incidence occurred in patient groups with the highest disease-free survival rates (P =.0378). 2) Highest incidence of delayed and distant metastases occurred in hypopharyngeal tumors and was three times greater than in laryngeal cancers (P =.028). 3) Salvage therapeutic rates were poor for delayed metastases to the ipsilateral treated nodes and distant metastases as compared with contralateral neck metastases and second primary tumors (P =.001). 4) Delayed and distant lymph node metastases were significantly higher in advanced primary disease (T4 stage), locoregional recurrences, and regional disease (N2 and N3) (P =.028) in both the larynx and hypopharynx. 5) The higher incidence of delayed and distant metastatic disease was related to more advanced initial tumor presentation in hypopharyngeal cancer as compared with laryngeal cancer (P =.039). 6) Incidence of distant metastases was greatest between 1.5 and 6 years after initial treatment with a mean incidence being less than or equal to 3.2 years.     

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.     

The value of chest CT-scanning for staging of progressed or recurrent head and neck squamous cell carcinomas (HNSCC)

AIM: At time of diagnosis, up to 17 % of HNSCC present with distant metastasis or a second primary tumour. Distant metastases of these tumours most commonly occur in the lung, requiring a particularly precise evaluation of this organ within the staging process. It was the aim of this study to compare the radiological findings of plain chest X-rays with the results of CT-scans of the chest in regard to their sensitivity for metastasis detection. PATIENTS AND METHODS: The staging examinations of 47 patients (f: 13, m: 34, mean age: 61.6 y) with progressed (T3, T4, N+) or recurrent HNSCC were prospectively analysed and results of chest X-rays as well as CT-scans of the chest compared. RESULTS: Only one plain chest X-ray showed a possible metastasis, which was excluded by the following CT-scan. In none of the other 46 patients did X-ray reveal findings of metastatic disease or second primary tumours. CT-scans of the chest showed tumorous lesions in 8/47 (17 %) patients. Three of these tumours were confirmed as neoplastic by biopsy, in another case radiological signs and clinical symptoms permitted definite assumption of malignancy (4/47 : 8.5 %). Histologically, only one of the latter four tumours could be identified as metastatic. In the remaining three cases we found second primary tumours. A follow up CT-scan of one of the remaining four cases showed normal results. In 3 cases the aetiology of the CT-findings remained unclear. CONCLUSION: Cervical lymph node metastases, tumour-size and recurrence of HNSCC are known risk factors for metastatic disease in HNSCC. Chest X-ray as staging procedure in patients with progressed or recurrent HNSCC may not be able to identify metastases or a second primary tumour of the lung. We therefore recommend a CT-scan of the chest as a routine procedure in such patients to optimise the pre-operative staging.