Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx

<p>Abstract</p> <p>Background</p> <p>Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections.</p> <p>Objectives</p> <p>To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease.</p> <p>Methods</p> <p>E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance.</p> <p>Results</p> <p>pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (<it>p </it>= 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (<it>p </it>= 0.005) in univariate and multivariate analysis.</p> <p>Conclusion</p> <p>These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx.</p> <p><b>Level of evidence: 2b</b></p

High sex determining region Y-box 2 expression is a negative predictor of occult lymph node metastasis in early squamous cell carcinomas of the oral cavity

BACKGROUND: The transcription factor sex determining region Y (SRY)-box 2 (SOX2) (3q26.3-q27) has been recently identified as a recurrently activated major oncogene in squamous cell carcinoma of various sites. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is currently unclear. AIM: To correlate SOX2 protein expression with the occurrence of occult lymph node metastasis and relapse free survival in early oral SCC. METHODS: SOX2 expression in 120 T1/T2 oral SCC patients was evaluated using a tissue microarray technique. Intensity of SOX2 expression was quantified by assessing the Intensity/Reactivity Scores (IRSs). These scores were correlated with the lymph node status of biopsied sentinel lymph nodes and recurrence. Log rank univariate and Cox regression multivariate analysis was used to determine statistical significance. RESULTS: Twenty-six of 120 primary tumours (21.7%) showed high SOX2 expression. High expression levels of SOX2 significantly correlated with negative lymph node status in univariate (p=0.001) and multivariate analysis (p=0.003). Sensitivity was found to be 95.6% with a negative predictive value of 92.3%. Specificity was 32% with a positive predictive value of 45.7%. CONCLUSION: SOX2 up-regulation is frequent in early SCC of the oral cavity and associated with decreased risk of lymphatic metastasis. SOX2 immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity

Long-term experience in sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma

OBJECTIVE: Long-term results of sentinel node biopsy (SNB) in early (T1/T2) oral and oropharyngeal squamous cell carcinoma (OSCC) in a single-institution experience. METHODS: Prospective consecutive cohort analysis of 79 patients (67% male, median age 60 years, age range 34-87 years) included between 2000 and 2006. Lymphatic mapping consisted of preoperative lymphoscintigraphy, single photon emission computed tomography (SPECT/CT), and intraoperative use of a handheld gamma probe. Endpoints of the study were neck control rate, overall (OS), disease-specific (DSS), and disease-free survival (DFS). RESULTS: Twenty-nine of 79 patients (37%) had positive sentinel nodes (SN). Six of 29 (21%) patients showed isolated tumor cells, 14/29 (48%) micrometastases, and 9/29 (31%) macrometastases. OS, DFS, and DSS at 5 years for the entire cohort were 80, 85, and 87%, for SN-negative patients were 88, 96, and 96%, and for SN-positive patients were 74, 73, and 77%, respectively. Only the difference in DSS achieved statistical significance. The neck control rate after 5 years was 96% in SN-negative and 74% in SN-positive patients. This difference was statistically significant. CONCLUSIONS: SNB is a safe and accurate staging modality to select patients with clinically stage I/II OSCC with occult lymph node disease for elective neck dissection (END). The promising reported short-term results have been sustained by long-term follow-up. Patients with negative SN and no END achieve an excellent neck control rate which compares favorably with reports on primary END. The neck control rate in SN-negative patients is superior to that in SN-positive patients, which is reflected in superior DSS

Evaluation of clinical and histomorphological parameters as potential predictors of occult metastases in sentinel lymph nodes of early squamous cell carcinoma of the oral cavity

BACKGROUND: Sentinel node biopsy (SNB) for cN0 early squamous cell carcinoma (SCC) of the oral cavity has been validated by numerous studies. Around 30% of SNB will detect occult disease. Several clinical and morphological features of the primary tumor have been claimed to be predictive for occult metastasis in elective neck dissections. The aim of this study was to assess these factors in the context of SNB. METHODS: Seventy-eight patients undergoing SNB for T(1/2) oral SCC from the years 2000 to 2007 were prospectively included. Primary tumors were reviewed for the following morphological and clinical parameters: grade of differentiation, tumor depth, tumor thickness, perineural invasion, lymphatic invasion, vascular invasion, muscle invasion, lymphoplasmacytic infiltration, and mode of invasion, age, gender, primary tumor site, tumor side, and cT category. RESULTS: Statistical analysis revealed significance to predict occult metastasis in the SNB for grade of differentiation (P = 0.002), lymphatic invasion (P < 0.001), and mode of invasion (P < 0.001). None of the other factors reached significance. The mean tumor depth was 6.45 mm (range 0.72-15.15 mm) and the mean tumor thickness was 7.2 mm (range 0.72-15.15 mm). None of the cutoff values reached significance for predicting occult disease. CONCLUSIONS: Tumor depth and tumor thickness failed to achieve statistical significance for prediction of occult metastases in the context of SNB. Patients with cN0 early squamous cell carcinoma of the oral cavity should be offered SNB regardless of their tumor depth and thickness. Poorly differentiated carcinomas, carcinomas with lymphangiosis, and carcinomas with a dissolute mode of invasion show a high probability of positive SNB