Unknown Primary Head and Neck Squamous Cell Carcinoma: Molecular Identification of the Site of Origin

Califano, Joseph A.; Westra, William H.; Koch, Wayne M.; Meininger, Glenn; Reed, Andre L.; Yip, Lin; Boyle, Jay O.; Lonardo, Fulvio; Sidransky, David

doi:10.1093/jnci/91.7.599

Cited by 130 publications

(76 citation statements)

References 12 publications

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“…1). 21 These findings are in keeping with the previous findings, by microsatellite analysis, of Califano et al, 55 who used this technique to identify possible sites of origin of unknown primary head-and-neck squamous cell carcinomas. Their findings are also substantiated by studies on copy number changes detected by comparative genomic hybridization, where a gain in chromosomes 12 and 14 and a loss in chromosomes 5, 6 and 21 significantly correlated with malignant transformation in oral leukoplakias.…”

Section: R E T R a C T E Dsupporting

confidence: 85%

Retracted: Impact of genomic instability in risk assessment and chemoprevention of oral premalignancies

Reith¹,

Sudbø²

2002

Intl Journal of Cancer

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Head-and-neck cancer is a disfiguring disease with increasing incidence rates even in young people, whose exposure to known risk factors is limited. This emphasizes the importance of early identification, on an individual basis, of precursor lesions that will develop into carcinomas. The clinical value of identifying individuals at high risk of oral cancer is emphasized by the fact that these patients are likely to benefit from available chemopreventive measures, largely without adverse effects. © 2002 Wiley-Liss, Inc. Key words : premalignant oral lesion; cancer risk; early diagnosis; prognosis; DNA ploidy; gross genomic aberration; chemoprevention; Oral squamous cell carcinomas have high mortality and morbidity and afflict an estimated 500,000 patients annually worldwide. [1][2][3][4] The incidence of oral carcinomas is especially high and increasing in developing countries. However, it is also increasing in Western countries, 5 substantially among younger people. 6 -8 Most cancers of the oral cavity are preceded by readily detectable white or red patches in the mucosal lining. The simple and straightforward detection of putative premalignant lesions gives a unique opportunity for identification of a malignant process and curative intervention at an early stage of oral carcinogenesis. Despite important advances in the field of head-and-neck oncology over the last decade, 9,10 identifying the subset of oral lesions that will progress to oral squamous cell carcinomas has remained a challenge. Reliable identification of lesions that are destined to become invasive cancers is possible. 11,12 Progress in determining the malignant potential of oral lesions allows more efficient chemopreventive treatment. 13 This review focuses on some diagnostic possibilities in premalignancies of the head and neck and on aspects of their molecular biology that may influence therapeutic approaches.PREMALIGNANT LESIONS OF THE ORAL MUCOSA Leukoplakias are frequently encountered lesions with a documented potential for transformation into oral squamous cell carcinomas. 14 -17 Erythroplakias, which are far rarer than leukoplakias, are considered to have a higher rate of malignant transformation (in some reports as high as 90%). 15 Detection of red or white patches does not require very sophisticated equipment or a particularly high degree of compliance from the patient. Since the days of Virchow, considerable knowledge of the morphologic manifestations of malignant genotypic changes has accumulated. In lesions of the oral cavity, the histologic finding of dysplasia has been considered to signal increased risk of malignant transformation. However, there is considerable uncertainty in the classification and grading of oral dysplasia, 18 -20 and several studies suggest that early and significant genetic changes do not necessarily correlate with observable morphologic changes within the mucosa. 11,12 Such changes have been detected and shown to signal subsequent transformation into manifest carcinoma, even in lesions classified as bei...

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Section: R E T R a C T E Dsupporting

confidence: 85%

Retracted: Impact of genomic instability in risk assessment and chemoprevention of oral premalignancies

Reith¹,

Sudbø²

2002

Intl Journal of Cancer

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“…Attention should be paid, instead, to the identification of subsets of patients who may benefit from this approach. Many efforts are now being made in the direction of molecular testing of tumour samples, both as an aid to diagnosis and as an adjunct to available clinical variables that can be used to select groups of patients well defined with regard to prognosis and sensitivity to chemotherapy (Bar-Eli et al, 1993;Motzer et al, 1995;Pavlidis et al, 1995;Briasoulis et al, 1998b;Califano et al, 1999;Hainsworth et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

et al. 2004

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The aim of this study was to assess the activity and toxicity of a platinum-based treatment on a group of patients with unknown primary tumours (UPTs). Patients with a diagnosis of UPT underwent a standard diagnostic procedure. Treatment was started within 2 weeks from diagnosis and consisted of carboplatin 400 mg m À2 day 1, doxorubicin 50 mg m À2 day 1, etoposide 100 mg m À2 days 1 -3, every 21 days. Response was evaluated after three courses and treatment continued in case of objective response (OR) or symptom control. A total of 102 patients were eligible. The median age was 59 years, sex male/female 54/48, histology was mainly adenocarcinoma or poorly differentiated carcinoma. Nodes, bone, liver and lung were the most frequently involved sites. In all, 79 patients received at least three courses of treatment; 26 patients received six courses or more. Six complete responses and 21 partial responses were observed, for a total of 27 of 102 ORs or 26.5% (95% confidence interval 18.2 -36.1%). The median survival was 9 months and median progression-free survival was 4 months. Toxicity was moderate to severe, with 57.8% of patients experiencing grade III -IV haematological toxicity, mainly leucopenia. The regimen employed has shown activity in tumours of unknown primary site, but was associated with significant toxicity. Such toxicity may be considered unjustified, given the large proportion of patients with tumours not likely to respond. Efforts should therefore be addressed to identify predictors of response to chemotherapy, thus limiting aggressive treatment to those patients who could benefit from it.

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“…more, similar genetic alterations were found in so called normal oral cavities and in lymph node metastases in some cases of occult primary tumors that, when analyzed within the context of field cancerization and clonal expansion, are strong evidence supporting the hypothesis of their origin in the upper digestive tract and the upper airway epithelium, with possible regression or tumor dormancy in the primary site [8][9][10] . Many studies report the association between microvascular density in primary tumors and metastases 3,4 .…”

Section: Resultsmentioning

confidence: 79%

Reatividade linfonodal e densidade microvascular nas metástases cervicais de carcinoma epidermóide com tumor primário oculto

Amar

Giovanini

Rosas

et al. 2006

Rev. Bras. Otorrinolaringol.

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INTRODUÇÃO: A neoangiogênese e a resposta imunológica são mecanismos importantes no desenvolvimento das metástases. OBJETIVO: Avaliar a reatividade linfonodal e a densidade microvascular nas metástases cervicais de carcinoma epidermóide com tumor primário oculto, considerando a sua relação com outras variáveis histológicas e clínicas. TIPO DE ESTUDO: Série de casos, retrospectiva. CASUÍSTICA E MÉTODO: 19 pacientes submetidos a esvaziamento cervical entre 1983 e 2000. Os linfonodos foram reavaliados quanto ao tipo de reatividade, considerando a área cortical e paracortical. Nas metástases foi avaliado o grau de diferenciação, desmoplasia, necrose, e densidade microvascular (CD34). Foi estabelecida a relação entre as diferentes variáveis histológicas e clínicas, incluindo o estadiamento e a evolução dos pacientes. RESULTADOS: A densidade microvascular apresentou mediana de 91 vasos/mm2, variando de 28 a 145. A reatividade paracortical foi mais freqüente nos pacientes com menos de 55 anos (90% x 44%, p= 0,05). A sobrevida livre de doença foi de 52% em 3 anos, sendo similar entre os pacientes com maior ou menor densidade microvascular tumoral. CONCLUSÕES: A densidade microvascular nas metástases de tumor primário oculto apresenta grande variação individual. Não foi possível estabelecer relação entre a densidade microvascular e as variáveis clínicas e histológicas estudadas.

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Unknown Primary Head and Neck Squamous Cell Carcinoma: Molecular Identification of the Site of Origin

Cited by 130 publications

References 12 publications

Retracted: Impact of genomic instability in risk assessment and chemoprevention of oral premalignancies

Retracted: Impact of genomic instability in risk assessment and chemoprevention of oral premalignancies

Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

Reatividade linfonodal e densidade microvascular nas metástases cervicais de carcinoma epidermóide com tumor primário oculto

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