Molecular Diagnosis of Surgical Margins and Local Recurrence in Head and Neck Cancer Patients

Abstract

Purpose: Approximately 10 -30% of surgically treated head and neck cancer patients develop local recurrences while the resection margins are histologically tumor free. These recurrences may arise from cancer cells left behind but not detected by the pathologist, or they may develop from precursor lesions adjacent to the tumor that were not completely resected. We have investigated whether TP53-mutated DNA in the surgical margins is suitable to identify patients with head and neck squamous cell carcinoma at risk for local and locoregional recurrence.Experimental Design: In a prospective cohort study of 76 patients with histologically tumor-free margins, the presence of TP53-mutated DNA was determined in the surgical margins using the phage plaque assay and correlated to clinical outcome. Immunostaining of the molecular-positive margins for mutated p53 protein was used to identify whether unresected precursor lesions or residual tumor cells were left behind.Results: The absence of TP53-mutated DNA in surgical margins was significantly associated with remaining free of local and locoregional recurrence (P ‫؍‬ 0.027 and P ‫؍‬ 0.028, respectively). Moreover, the presence of TP53-mutated DNA in the surgical margins was an independent prognosticator for locoregional recurrence (relative risk ‫؍‬ 7.1; P ‫؍‬ 0.021; 95% confidence interval, 0.9 -56). In 20% of the cases, the presence of TP53-mutated DNA in the surgical margins was found to be related to the presence of tumor-related precursor lesions.Conclusions: This study shows the value of TP53-mutated DNA as a molecular marker to predict locally recurrent head and neck squamous cell carcinoma. The observation that all patients who were negative for TP53-mutated DNA in the surgical margins remained free of local recurrence raises hope that molecular analysis of histologically tumor-free surgical margins can be exploited to decide on postoperative radiotherapy. Furthermore, our data provide evidence that local recurrences originate mainly from tumor cells left behind but also originate, in part, from unresected precursor lesions.

p53 Expression Helps Identify High Risk Oral Tongue Premalignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases

“…Earlier studies have shown that p53 overexpression screened by the same antibody used in the current study to evaluate positive tumour margins could be used to predict local recurrence. This study additionally showed that a small cluster of p53-positive carcinoma cells could be observed that was already present in the routine H&E staining but was missed by routine histology (Houten et al, 2004).…”

Clinical application of fluorescence endoscopic imaging using hypericin for the diagnosis of human oral cavity lesions

“…Second, it might be difficult to determine the margins of lesions during procedures. Moreover, genetically altered cells have been found to extend into clinically and histologically 'normal' regions (van Houten et al, 2004;Poh et al, 2006). Third, histopathology requires time for processing.…”

An Australian Retrospective Study to Evaluate the Prognostic Role of p53 and eIF4E Cancer Markers in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC): Study Protocol

“…One study has reported that eIF4E overexpression found in cancer tissue than the normal mucosa by using IHC (Rosenwald et al, 2001). Association between p53 and eIF4E expression and clinical outcomes A previous study suggests that IHC staining with p53 has an advantage over histopathology to identify the patients at high risk for local recurrence (Van Houten et al, 2004). This finding indicate some limitations of histological diagnosis and the potential for molecular markers to guide clinicians in the management of HNSCC (Nathan et al, 2000).…”

“…Significantly, five year survival rate in HNSCC is lower than other cancers, such as those of colorectal, cervix, and breast origin, due to detection of advanced stage disease (Jemal et al, 2008;Clark et al, 2010). With advent of new surgical procedures, improved radiotherapy and concomitant chemotherapy, there is a considerable improvement in local recurrence (Van Houten et al, 2004). However, the survival rates for HNSCC have not significantly improved (Partridge et al, 2007;Argiris et al, 2008).…”