Distinguishing Second Primary Tumors From Lung Metastases in Patients With Head and Neck Sauamous Cell Carcinoma

Leong, Paul P.; Rezai, Banafsheh; Koch, Wayne M.; Reed, Andre L.; Eisele, David W.; Lee, Ding Jen; Sidransky, David; Jen, Jin; Westra, William H.

doi:10.1093/jnci/90.13.972

Cited by 163 publications

(102 citation statements)

References 18 publications

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“…Hence, extrapolation of our validation data to all tumor pairs, including those that are TP53 wild-type, should be done with caution, and this is also a reason that our algorithm for interpretation of LOH results allows some discordant LOH. It has been suggested that in multiple chromosomes, breakpoints should be relied upon instead of LOH patterns (16). However, in our previous study, we showed that even breakpoint analyses might lead to misinterpretations, particularly when TP53 is wild-type (12).…”

Section: Discussionmentioning

confidence: 71%

“…We further evaluated whether immunohistochemical analysis of p53 expression in the SCC of both the head and neck and lung could be of help, at least as an initial quick screen. Positive immunostaining for p53 is presumptive evidence for gene mutation, as more than 90% of missense mutations will result in abnormal p53 protein accumulation (16). Immunohistochemistry is a simple and fast technique, and easily implemented at any pathology laboratory.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies showed lower percentages of SPT compared with DM (3 of 9 that could be differentially diagnosed reliably; ref. 16). The high ratio of SPT in our study is likely due to the selection criteria of the patient group and the retrospective nature of the study.…”

Section: Discussionmentioning

confidence: 99%

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Differential Diagnosis of Pulmonary Carcinoma Following Head and Neck Cancer by Genetic Analysis

Geurts

Velthuysen

Broekman

et al. 2009

Clinical Cancer Research

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Purpose: Patients with head and neck cancer often develop a lung tumor that can be diagnosed as distant metastasis (DM) or second primary tumor (SPT). In this study, we useTP53 mutation analysis for validation of an allelic loss marker panel and a decision algorithm for distinguishing between DM and SPT. Experimental Design: Tumor pairs of 39 patients were analyzed for TP53 mutations, for patterns of allelic loss and immunohistochemical analysis of p53 expression. Results of these three analyses were compared, using mutation analysis as gold standard. Results: Loss of heterozygosity (LOH) analysis indicated DM in 15 and SPT in 23 cases (one inconclusive). TP53 mutation analysis was informative in 15 cases. Based on the p53 mutation status alone, nine tumors were diagnosed as SPT and six as DM. In all 15 cases the LOH analysis was in concordance with the TP53 mutation analysis. Immunostaining for p53 showed promise as a first scan to diagnose lung tumors as SPT but cannot be used to diagnose DM. Conclusion: The TP53 mutation data validate the suitability of the LOH marker panel and decision algorithm for differential diagnosis of DM and SPT in the lung. LOH analysis can theoretically be exploited in almost all cases and is less laborious thanTP53 mutation analysis.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

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Differential Diagnosis of Pulmonary Carcinoma Following Head and Neck Cancer by Genetic Analysis

Geurts

Velthuysen

Broekman

et al. 2009

Clinical Cancer Research

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“…In this study, we used microsatellite markers on 11 different chromosome arms, whereas others analyzed multiple markers on two to six chromosome arms (6,10,27,28). In general, clonality was decided on the basis of concordant LOH of at least two loci, whereas in some articles the additional criterion of identical p53 mutations was used, if present (6,10,27,28).…”

Section: Discussionmentioning

confidence: 99%

“…In general, clonality was decided on the basis of concordant LOH of at least two loci, whereas in some articles the additional criterion of identical p53 mutations was used, if present (6,10,27,28). This approach, however, overlooks the phenomenon that LOH on different loci is not an independent process as we and others (17) have shown.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Squamous Cell Carcinoma following Head and Neck Squamous Cell Carcinoma: Metastasis or Second Primary?

Geurts

Nederlof²,

Brekel

et al. 2005

Clinical Cancer Research

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Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a squamous cell carcinoma of the lung, clinical data, histology, and analysis of loss of heterozygosity (LOH) were used to differentiate metastases from second primary tumors. Results: Clinical evaluation suggested 38 patients with metastases and 6 with second primaries. We developed a novel interpretation strategy based on biological insight and on our observation that multiple LOH on different chromosome arms are not independent. LOH analysis indicated metastatic disease in 19 cases and second primary squamous cell carcinoma in 24 cases. In one case, LOH analysis was inconclusive. For 25 patients, LOH supported the clinical scoring, and in 18 cases, it did not.These18 discordant cases were all considered to be second primary tumors by LOH analysis. Conclusions: A considerable number of squamous cell lung lesions (50% in this study), clinically interpreted as metastases, are suggested to be second primaries by LOH analysis. For these patients, a surgical approach with curative intent may be justified.Patients treated for head and neck squamous cell carcinoma frequently develop second primary tumors in the lung (1 -3). Because the histologic appearance of the head and neck tumor and the lung lesion is similar (squamous cell carcinoma in both cases), the differential diagnosis between second primary or metastasis is mainly dependent on clinical criteria such as localization of the lung lesion, tumor stage, and disease-free interval. Warren and Gates (4) were the first to develop criteria for second primary tumors and additional studies have been published since (summarized in Table 1). The criteria employed, such as histology, tumor stage, and interval, however, do not give a definitive answer in the differential diagnosis mentioned above.Treatment options for patients with second primary lung tumors are different from those for metastasized head and neck squamous cell carcinoma. A resectable second primary would justify surgical approach with curative intent (5 -9), whereas metastatic disease would be treated with systemic therapy or limited surgical resection. Therefore, we looked for the identification of more objective markers in this differential diagnosis.In theory, clonal relationship between two tumors proves their common origin in case of metastases. Conversely, the absence of a clonal relationship would suggest a second primary carcinoma. Many assays have been developed to evaluate clonal relationship between tumors. Analysis of patterns of loss of heterozygosity (LOH) has been used to distinguish second primaries from metastases in the aerodigestive tract (10 -12). LOH analysis is easy to perform on paraffinembedded tissue and, thus, potentially very useful in everyday clinical practice, as well as for the ...

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Quantitative proteomics identifies biomarkers to distinguish pulmonary from head and neck squamous cell carcinomas by immunohistochemistry

Richter¹,

Fichtner²,

J³

et al. 2021

The Journal of Pathology CR

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The differentiation between a pulmonary metastasis and a newly developed squamous cell carcinoma of the lung in patients with prior head and neck squamous cell carcinoma (HNSCC) is difficult due to a lack of biomarkers but is crucially important for the prognosis and therapy of the affected patient. By using high-resolution mass spectrometry in combination with stable isotope labelling by amino acids in cell culture, we identified 379 proteins that are differentially expressed in squamous cell carcinomas of the lung and the head and neck. Of those, CAV1, CAV2, LGALS1, LGALS7, CK19, and UGDH were tested by immunohistochemistry on 194 tissue samples (98 lung and 96 HNSCCs). The combination of CAV1 and LGALS7 was able to distinguish the origin of the squamous cell carcinoma with high accuracy (area under the curve 0.876). This biomarker panel was tested on a cohort of 12 clinically classified lung tumours of unknown origin after HNSCC. Nine of those tumours were immunohistochemically classifiable.

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Distinguishing Second Primary Tumors From Lung Metastases in Patients With Head and Neck Sauamous Cell Carcinoma

Cited by 163 publications

References 18 publications

Differential Diagnosis of Pulmonary Carcinoma Following Head and Neck Cancer by Genetic Analysis

Differential Diagnosis of Pulmonary Carcinoma Following Head and Neck Cancer by Genetic Analysis

Pulmonary Squamous Cell Carcinoma following Head and Neck Squamous Cell Carcinoma: Metastasis or Second Primary?

Quantitative proteomics identifies biomarkers to distinguish pulmonary from head and neck squamous cell carcinomas by immunohistochemistry

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