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

Abstract

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.

Resection of secondary pulmonary malignancies in head and neck cancer patients

“…Although such techniques are time-consuming, they are becoming more and more suitable for routine application. [6][7][8] Reported five-year survival rates after resection of metachronous lung lesions range from 19 to 43 per cent; however, as in the current series, these percentages are still based on small patient cohorts (n ≤ 55). 4,5,[9][10][11] Winter et al found a significantly better survival, comparing operated and non-operated patients by matched pair analysis, in 67 patients with pulmonary metastases of head and neck cancer.…”

“…[6][7][8]32,33 However, these techniques are complex and sometimes time-consuming, and not universally available for pre-operative analysis of tumour tissue. Although one might have expected better survival rates after treatment for second primary lung cancer, compared with treatment for lung metastases, we were not able to demonstrate such a difference in a group of patients with molecularly defined lung SCC lesions.…”

“…As demonstrated in our previous publications on the molecular analysis of secondary pulmonary malignancies, histological differentiation between lung metastasis and second primary lung cancer is often difficult. 7,8 Survival was analysed from the date of resection of the secondary lung lesion(s) to the date of last followup or death, using the Kaplan-Meier method. In case of multiple resections, survival was calculated from the date of the first resection of a lung lesion.…”

HPV Analysis in Distinguishing Second Primary Tumors From Lung Metastases in Patients With Head and Neck Squamous Cell Carcinoma

“…This distinction greatly influences patient prognosis and could guide treatment strategies, but the nature of the lung nodule is often difficult to discern using standard clinical and histologic parameters. Some have advocated comparative analysis of various genetic parameters such as gene mutations or microsatellite alterations;(14,15,23,36) but implementation has been constrained by cost, technical considerations, and the inherent instability of a tumor’s genetic profile over time. HPV analysis is an attractive alternative given that HPV is an established causative agent for a subset of HNSqCCs, the incidence of these HPV-related HNSqCCs is rising to the point that they now dominate the head and neck oncology landscape, and HPV tumor analysis is relatively straightforward using widely available in-situ and immunohistochemical techniques.…”

“…Comparison of multiple tumors for patterns of microsatellite alterations, specific gene mutations and other molecular genetic parameters has been advocated as a better way to clarify the fundamental distinction between a second lung carcinoma and a lung metastasis. (14,15,23,36) Widespread integration of these novel strategies into routine clinical practice, however, has not been forthcoming. Transfer into the clinical arena has been limited by cost, technical feasibility, and the inherent instability of the genetic profile of a tumor over time.…”