Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity

The incidence of oral squamous cell carcinoma remains high. Oral and oro-pharyngeal carcinomas are the sixth most common cancer in the world. Several clinicopathological parameters have been implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma. In this retrospective analysis, clinicopathological parameters of 115 T1/T2 OSCC were studied and compared to recurrence and death from tumour-related causes.The study protocol was approved by the Joint UCL/UCLH committees of the ethics for human research. The patients' data was entered onto proformas, which were validated and checked by interval sampling. The fields included a range of clinical, operative and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death and last clinic review. Causes of death were collated in 4 categories (1) death from locoregional spread, (2) death from distant metastasis, (3) death from bronchopulmonary pneumonia, and (4) death from any non-tumour event that lead to cardiorespiratory failure.The patients' population comprised 65 males and 50 females. Their mean age at the 1st diagnosis of OSCC was 61.7 years. Two-thirds of the patients were Caucasians. Primary sites were mainly identified in the tongue, floor of mouth (FOM), buccal mucosa and alveolus. Most of the identified OSCCs were low-risk (T1N0 and T2N0). All patients underwent primary resection ± neck dissection and reconstruction when necessary. Twenty-two patients needed adjuvant radiotherapy. Pathological analysis revealed that half of the patients had moderately differentiated OSCC. pTNM slightly differed from the cTNM and showed that 70.4% of the patients had low-risk OSCC. Tumour clearance was ultimately achieved in 107 patients. Follow-up resulted in a 3-year survival of 74.8% and a 5-year survival of 72.2%.Recurrence was identified in 23 males and 20 females. The mean age of 1st diagnosis of the recurrence group was 59.53 years. Most common oral sites included the lateral border of tongue and floor of mouth. Recurrence was associated with clinical N-stage disease. The surgical margins in this group was evaluated and found that 17 had non-cohesive invasion, 30 had dysplasia at margin, 21 had vascular invasion, 9 had nerve invasion and 3 had bony invasion. Severe dysplasia was present in 37 patients. Tumour clearance was achieved in only 8 patients. The mean depth of tumour invasion in the recurrence group was 7.6 mm.An interesting finding was that 5/11 patients who died of distant metastasis had their primary disease in the tongue. Nodal disease comparison showed that 8/10 patients who died of locoregional metastasis and 8/11 patients who died from distant metastasis had clinical nodal involvement. Comparing this to pathological nodal disease (pTNM) showed that 10/10 patients and 10/11 patients who died from locoregional and distant metastasis, respectively, had nodal disease. All patients who died from locoregional and distant metastasis were shown to ...

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“…An inverse relationship was also reported by other studies, between lymphocytic infiltrate and nodal disease and overall prognosis [60,61]. …”

Section: Discussionsupporting

confidence: 82%

Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

et al. 2010

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“…Interestingly, this lack of association has been reported by other studies [26,27]. We do not feel that HOXA1 was sufficiently studied in its role in tumor prognosis in OSCC or other malignancies, however, several studies have reported that lymph node metastasis is the most reliable marker of OSCC patient prognosis [28-30], and our findings showed that the presence of lymph node metastasis significantly correlated with high HOXA1 expression and both were significant prognostic factors for overall survival by multivariate analysis. Since HOXA1 is expressed in a number of cancers, our findings encourage its verification and monitoring in other malignancies.…”

Section: Discussioncontrasting

confidence: 57%

HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

et al. 2012

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BackgroundHOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer.MethodsIn order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression.ResultsWe showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026).ConclusionOur findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1 expression might be helpful as a prognostic marker for patients with OSCC.

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“…The survival rates for patients without lymph node metastasis and those with lymph node metastasis were 94 and 51 per cent, respectively. 24 It is therefore of immense clinical importance to predict the invasive and metastatic potential of oral SCCs.…”

Section: Discussionmentioning

confidence: 99%

Ets‐1: a plausible marker of invasive potential and lymph node metastasis in human oral squamous cell carcinomas

et al. 1999

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The proto‐oncogene Ets‐1 is a transcription factor known to regulate the expression of a number of genes involved in extracellular matrix remodelling. It has been postulated to play a role in angiogenesis, cell migration, and regulation of tumour invasion. In betel and tobacco‐related oral tumourigenesis, oral squamous cell carcinomas (SCCs) having a poor prognosis often exhibit extensive local disease with spread into regional lymph nodes. At present, no tumour marker is available to predict the metastatic potential of oral carcinomas. To elucidate the involvement of Ets‐1 in human oral tumourigenesis, 60 cases of oral SCC, 30 potentially malignant lesions, and 30 samples of normal oral mucosa were examined by immunohistochemistry and the findings corroborated with immunoblotting. The relationship of Ets‐1 expression with the degree of differentiation, lymph node metastasis, and tumour stage was determined in oral SCCs. Ets‐1 was not detected in the normal oral epithelium. Among the 60 cases of oral SCC, 35 cases (58 per cent) showed positive staining for the Ets‐1 protein in tumour cells. In potentially malignant lesions, 14 of 30 cases (47 per cent) showed Ets‐1 immunopositivity. Ets‐1 expression correlated significantly with tumour stage ( p=0·01) and lymph node metastasis ( p=0·005). The presence of Ets‐1 mRNA in oral SCCs was confirmed by reverse transcription‐polymerase chain reaction (RT‐PCR). These findings suggest that overexpression of Ets‐1 in potentially malignant lesions may be related to angiogenesis and its expression in oral SCCs may be one of the factors involved in tumour progression and lymph node metastasis. Copyright © 1999 John Wiley & Sons, Ltd.

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Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity

Cited by 121 publications

References 24 publications

Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

Ets‐1: a plausible marker of invasive potential and lymph node metastasis in human oral squamous cell carcinomas

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