Genetic diagnosis of micrometastases in cervical lymph nodes of head and neck cancer.

Hamakawa, Hiroyuki; Fukuzumi, Masakuni; Bao, Yan; Tanioka, Hiroaki; Sato, Masateru; Yumoto, Eiji

doi:10.5981/jjhnc1974.25.81

Cited by 23 publications

(31 citation statements)

References 11 publications

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“…We and others have previously shown that RT-PCR can potentially be more sensitive than routine pathology for analysis of lymph nodes (7,26,28). In head and neck cancer specifically, studies on molecular analysis of cervical lymph node metastasis have used a variety of techniques, including PCR amplification to detect p53 mutations (45), immunohistochemistry staining (with or without serial sectioning) and histopathologic examination (14)(15)(16), and standard RT-PCR-based analysis of tumor maker gene expression (46). More recently, several groups have used quantitative RT-PCR for detection of cervical lymph node metastases (8,47) and Nieuwenhuis et al showed the prognostic value of QRT-PCR in pN0 SCCHN patients (33).…”

Section: Discussionmentioning

confidence: 99%

Molecular Staging of Cervical Lymph Nodes in Squamous Cell Carcinoma of the Head and Neck

Ferris

Raja³

et al. 2005

Cancer Research

101

119

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Clinical staging of cervical lymph nodes from patients with squamous cell carcinoma of the head and neck (SCCHN) has only 50% accuracy compared with definitive pathologic assessment. Consequently, both clinically positive and clinically negative patients frequently undergo neck dissections that may not be necessary. To address this potential overtreatment, sentinel lymph node (SLN) biopsy is currently being evaluated to provide better staging of the neck. However, to fully realize the potential improvement in patient care afforded by the SLN procedure, a rapid and accurate SLN analysis is necessary. We used quantitative reverse transcription--PCR (QRT-PCR) to screen 40 potential markers for their ability to detect SCCHN metastases to cervical lymph nodes. Seven markers were identified with good characteristics for identifying metastatic disease, and these were validated using a set of 26 primary tumors, 19 histologically positive lymph nodes, and 21 benign nodes from patients without cancer. Four markers discriminated between positive and benign nodes with accuracy > >97% but only one marker, pemphigus vulgaris antigen (PVA), discriminated with 100% accuracy in both the observed data and a statistical bootstrap analysis. A rapid QRT-PCR assay for PVA was then developed and incorporated into a prototype instrument capable of performing fully automated RNA isolation and QRT-PCR. The automated analysis with PVA provided perfect discrimination between histologically positive and benign lymph nodes and correctly identified two lymph nodes with micrometastatic tumor deposits. These assays were completed ( from tissue to result) in f f30 minutes, thus demonstrating the feasibility of intraoperative staging of SCCHN SLNs by QRT-PCR. (Cancer Res 2005; 65(6): 2147-56)

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Section: Discussionmentioning

confidence: 99%

Molecular Staging of Cervical Lymph Nodes in Squamous Cell Carcinoma of the Head and Neck

Ferris

Raja³

et al. 2005

Cancer Research

101

119

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“…CK5, CK14, CK19 mRNA) and markers that are known to be differentially expressed between HNSCC and normal irrespective of their function (i.e. E48, SCCA, PVA, PTHrP) [15][16][17]. While initial studies evaluated simply the presence or absence of transcript [16,17] as denoting positivity, with the introduction of quantitative RT-PCR [12,15] validated cutoff levels discriminating between positive and negative results can be generated.…”

Section: Molecular Approachmentioning

confidence: 99%

“…While initial studies evaluated simply the presence or absence of transcript [16,17] as denoting positivity, with the introduction of quantitative RT-PCR [12,15] validated cutoff levels discriminating between positive and negative results can be generated. Using these approaches, 'molecular positive' lymph nodes can be seen in as many as 20-30% of cases that are negative by light microscopy and immunohistochemistry [12,[14][15][16][17]. A small fraction of these cases have been validated by further serial sectioning to detect micrometastases or ITC previously not identified by initial H&E.…”

Section: Molecular Approachmentioning

confidence: 99%

Current State of Neck Dissection in the United States

Seethala

2009

Head and Neck Pathol

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The status of the cervical lymph nodes is the most important prognosticator in head and neck squamous cell carcinoma. The neck dissection is both a therapeutic and staging procedure and has evolved to include various types with standardized level designations (I-VI) for lymph node groups: the radical neck dissection, modified radical neck dissection, the selective neck dissection, and the extended neck dissection. The gross and histologic examination of a neck dissection should provide the critical information (size of metastasis, number of lymph nodes involved) for staging purposes. Additionally, extracapsular spread of lymph node metastasis must be reported because of its significance as an adverse prognosticator. Current dilemmas in nodal disease are the detection of micrometastases, isolated tumor cells, and molecular positivity. The significance of these categories of disease is still unclear, though they may explain a subset of the estimated 10% of the regional recurrences in the neck despite pathologic node negativity by traditional methods of evaluation. Sentinel lymph node biopsy has been recently applied to head and neck squamous cell carcinoma to enhance the management of the clinicoradiographically node negative patients. While still investigational, sentinel lymph node biopsy shows promise in selecting patients who require a neck dissection. Rapid highly automated real-time RT-PCR based platforms will allow for incorporation of molecular findings into the intraoperative evaluation of a sentinel lymph node.

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“…Hamakawa et al [6] reported that 37 of 198 histologically metastasis-negative nodes (18.7%) of patients with squamous cell carcinoma of the head and neck had micrometastases disclosed by genetic diagnosis based on squamous cell carcinoma antigen mRNA. Eleven micrometastatic foci in 9 lymph nodes (4.6%) were discovered by semiserial sections with hematoxylin and eosin staining and keratin immunostaining.…”

mentioning

confidence: 99%

“…Table 3 summarizes the reported studies in which occult micrometastases from patients with primary head and neck cancers were detected with a variety of different morphologic and nonmorphologic methods [1-3, 5, 7, 10-20]. Hamakawa et al [6] Detected by molecular techniques Brennan et al [5] Brennan and Sidransky [19] Partridge [20] Hamakawa et al [6] 1 Different papers regard similar series.…”

mentioning

confidence: 99%

What Is the Incidence of Occult Metastasis in Patients with Stage N₀ Cancers of the Head and Neck?

Ferlito

Devaney

et al. 2001

ORL

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There is a large body of evidence in the European and US literature which argues forcefully that the presence of metastatic deposits within cervical lymph nodes is the single most significant independent adverse prognostic factor in patients with squamous-cell carcinomas of the head and neck. When all head and neck cancers are considered, ipsilateral lymph node metastases appear to decrease patient survival by as much as 50%; moreover, the presence of contralateral or bilateral cervical metastases reduces prognosis by an additional 50%. Patients with cervical metastases seem to be more likely to develop both distant metastases and local recurrences at the primary site.

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Genetic diagnosis of micrometastases in cervical lymph nodes of head and neck cancer.

Cited by 23 publications

References 11 publications

Molecular Staging of Cervical Lymph Nodes in Squamous Cell Carcinoma of the Head and Neck

Molecular Staging of Cervical Lymph Nodes in Squamous Cell Carcinoma of the Head and Neck

Current State of Neck Dissection in the United States

What Is the Incidence of Occult Metastasis in Patients with Stage N₀ Cancers of the Head and Neck?

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Genetic diagnosis of micrometastases in cervical lymph nodes of head and neck cancer.

Cited by 23 publications

References 11 publications

Molecular Staging of Cervical Lymph Nodes in Squamous Cell Carcinoma of the Head and Neck

Molecular Staging of Cervical Lymph Nodes in Squamous Cell Carcinoma of the Head and Neck

Current State of Neck Dissection in the United States

What Is the Incidence of Occult Metastasis in Patients with Stage N&#8320; Cancers of the Head and Neck?

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What Is the Incidence of Occult Metastasis in Patients with Stage N₀ Cancers of the Head and Neck?