Cell Carcinoma Of Oral Tongue Research Articles

Epigenomic integrative analysis pinpoint master regulator transcription factors associated with tumorigenesis in squamous cell carcinoma of oral tongue.

Head and Neck Cancer (HNC) is a heterogeneous group of cancers, which includes cancers arising in the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. Epidemiological studies have revealed that several factors such as tobacco and alcohol use, exposure to environmental pollutants, viral infection, and genetic factors are risk factors for developing HNC. The squamous cell carcinoma of oral tongue (SCCOT), which is significantly more aggressive than the other forms of oral squamous cell carcinoma, presents a propensity for rapid local invasion and spread, and a high recurrence rate. Dysregulation in the epigenetic machinery of cancer cells might help uncover the mechanisms of SCOOT tumorigenesis. Here, we used DNA methylation changes to identify cancer-specific enhancers that were enriched for specific transcription factor binding sites (TFBS), and potential master regulator transcription factors (MRTF) associated with SCCOT. We identified the activation of MRTFs associated with increased invasiveness, metastasis, epithelial-to-mesenchymal transition, poor prognosis, and stemness. On the other hand, we found the downregulation of MRTFs associated with tumor suppression. The identified MRTFs should be further investigated to clarify their role in oral cancer tumorigenesis and for their potential use as biological markers.

Reconstruction of Partial Glossectomy Defects in Patients with Squamous Cell Carcinoma of Oral Tongue: A Prospective Clinical Study on the Assessment and Comparison of Intraoperative and Postoperative Outcomes of Islanded Nasolabial Flap Tunneled Under the Mandible and Radial Forearm Free Flap

Background: Reconstruction of the glossectomy defect following surgery plays a pivotal role in a patient’s quality of life. Reconstruction of surgical defects following glossectomy has evolved greatly from locoregional flaps such as nasolabial, submental, infrahyoid, and pectoralis major myocutaneous flaps to microvascular free flaps (radial forearm free flap [RAFF], anterolateral thigh flap). Due to certain drawbacks, microvascular-free flaps are avoided; instead, local/regional flaps are preferred. Islanded Nasolabial Flap Tunneled Under the Mandible (INFTUM) is a modification of the conventional nasolabial flap based on the facial artery. The flap is raised by dissecting to a certain length to adequately reach a significant distance for reconstruction of the glossectomy defects of mild-to-moderate size. This flap provides adequate bulk and pliable tissue to the remaining tongue, which aids in better functional outcomes. Aim: The aim is to assess and compare the intraoperative and postoperative outcomes of INFTUM and RAFF for the reconstruction of partial glossectomy defects in patients with squamous cell carcinoma of the oral tongue. Materials and Methods: This prospective study was conducted on 20 patients equally divided into two groups, Group A – Islanded Nasolabial Flap Tunnelled Under the Mandible and Group B – RAFF conducted in SGM Cancer Hospital, Sawangi. Intraoperative and postoperative outcomes were evaluated, and statistical analysis was performed using independent sample t-test and Chi-square test where values less than P = 0.05 were found significant. Results: INFTUM flap displayed better intraoperative and postoperative outcomes, especially functional outcomes, in shorter duration as it is locally available with minimum cosmetic deformity to the donor site. In this study, the flap is done in a single stage by tunneling under the mandible. It has a good reach to any aspect of the oral cavity, including the contralateral side, if ipsilateral level Ib nodes are compromised. Conclusion: INFTUM is a simple, effective, and safe flap that can be used for the reconstruction of T2-T3 lesions or partial glossectomy defects. It provides better intraoperative and postoperative outcomes and comparable functional outcomes to RAFF, especially when patients have anesthesia risk for prolonged surgical procedures in a limited-resource setting. Furthermore, it has comparatively less postoperative complications as it has less learning curve.

Depth of invasion (DOI) as a predictor of cervical nodal metastasis and local recurrence in early stage squamous cell carcinoma of oral tongue (ESSCOT).

BackgroundThe new AJCC staging system (8th edition) incorporates depth of invasion to stage oral cancers. It is a recognized predictor for neck nodal metastasis and local recurrence, the associated risk is not well defined. The aim of this study was to explore the risk of occult neck nodal metastasis and local recurrence in relation to depth in early stage squamous cell carcinoma of oral tongue.MethodsWe have evaluated records of 179 patients with early tongue cancer treated in our unit from 2006–2015 with a mean age of 57.92 ± 11.93 years. Treatment modalities used were surgery (26%), surgery followed by radiotherapy (64%) and chemo-radiation (10%). Neck dissection was ipsilateral in 94% and bilateral in 6% of the patients. Patients were grouped according to the AJCC cut off points in 8th edition for depth; group A: 1–5 mm (35%), group B: 6–10 mm (47%) and group C: > 10 mm (18%).ResultsRisk of local recurrence and nodal metastasis for Group A was 15% (10/63) and 23% (15/63), group B 20% (17/84) and 34% (29/84), and group C 40% (13/32) and 53% (17/32).ConclusionsDepth more than 10 mm is associated with significantly increased risk of recurrence and nodal metastasis. Elective neck dissection should be a consideration for tumors having depth less than 5mm.

The Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of Oral Tongue

Oral tongue Squamous Cell carcinoma (SCC) commonly involves males between the sixth to eighth decades of life. Major risk factors are tobacco usage and alcohol consumption. The increasing number of patients developing oral tongue cancer without these well-known risk factors suggests that a viral infection, such as Human Papillomavirus (HPV), may be responsible for this increase, by acting as an oncogenic agent. This study investigated the prevalence of HPV infection and its clinicopathologic significance in oral tongue SCCs. Tissue blocks from a total of 50 cases (patients with oral tongue SCC) and 50 controls (palatine tonsillar tissues with benign diagnosis) were selected. DNA was extracted from tumoral and non-tumoral tissue blocks. Detection of common HPV DNA by nested Polymerase Chain Reaction (PCR), and high-risk genotypes, HPV 16 and HPV 18, by conventional PCR, was achieved and the results correlated with clinicopathological parameters. Of the 50 patients (18 males and 32 females with a mean age of 57.36±12.18 years, and age range of 27 to 86 years), 7 (14%) had HPV positive results. None of the control group subjects had HPV DNA positive results (P-value of 0.012). The HPV genotype 16/18 was not detected in positive cases. No statistically significant association was found between HPV status and gender, age, tumor grade, tumor stage or lymph node involvement. Although there was a significantly higher prevalence of HPV in oral tongue SCC, its association with carcinogenesis in this area requires further studies.

Clinical outcome of surgical treatment of T1-2 N0 squamous cell carcinoma of oral tongue with observation for the neck: Analysis of 176 cases.

Objective:To analyze various demographic, clinical, and histopathologic factors in T1-2 N0 squamous cell carcinoma (SCC) of the oral tongue to define a high-risk group for regional recurrence that will benefit from elective neck dissection.Materials and Methods:Retrospective outcome analysis of a patient cohort without palpable or ultrasound (USG) detectable nodal metastases undergoing per oral wide glossectomy for T1-2 N0 SCC of oral tongue. Patients were followed up using palpation and serial USG neck and fine-needle aspiration cytology.Results:Of the 176 patients, 69 (39%) showed recurrence during follow-up. Fifty-eight cases developed regional neck node metastases, i.e., overall regional node recurrence rate of 33%. Fifty-three (91%) with regional neck node metastases were salvaged successfully with further treatment. In 110 cases with tumor thickness more than 5 mm, 39% cases developed regional neck node metastases. This association was significant with P = 0.0402. Among 44 cases with perineural invasion, 54% developed regional neck node metastases. Similarly in 39 cases with lymphovascular invasion, 61% developed regional neck node metastases. Association of both of these parameters with the development of regional neck node metastases was significant.Conclusion:We recommend prophylactic selective neck dissection in early stage SCC of oral tongue, especially with depth of invasion more than 5 mm, perineural and lymphovascular invasion.

Snail and Slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma.

microRNAs(miRNAs) can regulate epithelial-mesenchymal transition (EMT) through transcription factors, however, little is known whether EMT transcription factors can modulate miRNAs and further induce EMT and cancer metastasis. Here we show that overexpression of Snail and Slug leads to a mesenchymal phenotype and morphology and enhances cell invasion along with stem cell properties in squamous cell carcinoma of oral tongue (OTSCC) cells. Repression of miR-101 expression by Snail and Slug is essential for Snail/Slug-induced malignant phenotypes. The suppression of miR-101 subsequently activates EZH2, the sole histone methyltransferase, inducing EMT, migration and invasion of OTSCC cells. Importantly, co-overexpression of Slug and Snail correlates with poor survival and elevated EZH2 expression in two independent patient cohorts of OTSCC specimens. These findings defined a Snail and Slug/miR-101/EZH2 pathway as a novel regulatory axis of EMT-mediated-microRNA signaling.

CD147 and Ki-67 overexpression confers poor prognosis in squamous cell carcinoma of oral tongue: A tissue microarray study

Squamous cell carcinoma of the oral tongue (SCCOT) exhibits high risk for recurrence and regional metastasis even after surgical resection. We assessed the clinicopathologic and prognostic significance of a group of functionally related biomarkers. We used a tissue microarray consisting of SCCOT from 32 patients for this study. These patients were treated at the University of Texas MD Anderson Cancer Center from 1995 to 2008. Biomarker expression levels were examined by immunohistochemistry and graded semiquantitatively to determine their prognostic significance. CD147 and Tp63 expressions were significantly associated with a higher T stage and Ki-67 labeling index, as well as a shorter overall survival (OS) rate. Expression of Tp63 associated positively with poorly differentiated histology. There was significant association of Tp63 with the expression levels of CD147 and Glut-1. Glut-1 overexpression was marginally associated with a higher T stage. There was no prognostic significance of CD44 v6 expression in SCCOT. SCCOT with CD147 overexpression in combination with high Ki-67 labeling index had poor OS. CD147 and Ki-67 overexpression is associated with aggressive disease with poor prognosis in SCCOT.

TP53 Pro72 allele is enriched in oral tongue cancer and frequently mutated in esophageal cancer in India.

PurposeThe tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India.MethodsWe assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters.ResultsPro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg.ConclusionsOur study revealed the association of Pro72 allele with SCCOT suggesting the effect of this polymorphism on SCCOT risk. Preferential mutation of Pro72 allele exclusively in ESCC indicates the need for further studies to understand the tissue specific effect of p53 polymorphism.

P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue.

BackgroundSquamous cell carcinoma of tongue (SCCT) is expected to harbor unique clinico-pathological and molecular genetic features since a significant proportion of patients are young and exhibit no association with tobacco or alcohol.MethodsWe determined P53, epidermal growth factor receptor, microsatellite instability, human papilloma virus infection and loss of heterozygosity status at several tumor suppressor loci in one hundred and twenty one oral SCCT (SSCOT) samples and analyzed their association with clinico-pathological features and patient survival.ResultsOur results revealed a significantly higher incidence of p53 nuclear stabilization in early (as against late) onset SCCOT. FHIT loss was significantly associated with p53 nuclear stabilization and the association was stronger in patients with no history of tobacco use. Samples harboring mutation in p53 DNA binding domain or exhibiting p53 nuclear stabilization, were significantly associated with poor survival.ConclusionOur study has therefore identified distinct features in SCCOT tumorigenesis with respect to age and tobacco exposure and revealed possible prognostic utility of p53.

Cervical node metastasis in T1 squamous cell carcinoma of oral tongue- pattern and the predictive factors.

The squamous cell carcinoma (SCC) of the oral tongue is a common cancer in India. Elective lymphadenectomy is generally performed in all patients with T2-T4 tumors. In this study we have tried to analyze the pattern and risk factors associated with lymph node metastasis in T1 tongue cancers. A retrospective review of the records of 57 patients undergoing surgery for treatment of T1 sqamous cell carcinoma of oral tongue was carried out. The clinicopatological features of the tumor, pattern of nodal metastasis and the risk factors associated with lymph node metastasis were studied. Totally 57 patients with T1 tumor underwent excision of the primary and modified neck dissection (MND). Lymph node metastasis was found in 36.8% of the patients. Level I to Level II was the commonest site of metastasis. Skip metastasis at level III and IV was found in 8.5% of the patients and isolated skip metastasis at level IV in 1.5% of the patients. The risk factors associated with the lymph node metastasis on univariete analysis were; higher grade, tumor size >1cm and tumor thickness >3mm. On multivariate analysis only the tumor thickness was found to be a risk factor for the lymph node metastasis (hazard ratio of 21.59). T1 sqamous cell carcinoma of tongue is associated with a high incidence of lymph node metastasis. Elective neck dissection should be considered in all patients with tumors more than 3mm in thickness.

Predictors of prognosis for squamous cell carcinoma of oral tongue

Certain tumor-related factors like thickness increases the risk of nodal metastasis and may affect survival in patients with oral tongue cancers. The objective of this study is to identify those tumor-related prognostic predictors that can potentially influence decision for adjuvant radiotherapy. A retrospective review of all patients with oral tongue cancers treated primarily by surgery at Tata Memorial Hospital between January 2007 and June 2010. The demographic and commonly reported histopathological features were analyzed for their influence on disease free and overall survival. Five hundred eighty-six patients were eligible for the study, of which 416 were males and 117 were females. Follow-up details were available for 498 (85%) patients with a median follow-up of 18 months and mean follow-up of 22 months. There were 302 patients who were alive and disease free at the last follow-up. This group had a mean follow-up of 27 months and median follow-up of 27.5 months. Disease recurrences during follow-up were observed in 184 (31%) patients. Sixty-one patients died subsequently. Perineural invasion significantly affected disease free survival (DFS). A tumor thickness of more than 11 mm significantly affected the overall survival (OS). Other than nodal metastasis, tumor-related factors like thickness and perineural invasion are adverse prognostic factors and can influence survival. These patients, especially in case of early stage cancers, may potentially benefit from postoperative adjuvant radiotherapy. 2b.

Cervical lymph node metastasis from early-stage squamous cell carcinoma of the oral tongue

Conclusions: The findings of this study demonstrated that the wait-and-watch strategy for neck metastasis from squamous cell carcinoma (SCC) of oral tongue is a reliable option and that salvage by surgical treatment is effective. However, younger patients should be closely monitored for recurrence. Adjuvant therapy may be recommended for patients with pathologically advanced disease. Objectives: Metastatic involvement of cervical lymph nodes is the most important prognostic indicator in patients with oral tongue SCC. With the objective of determining the most appropriate treatment strategy for regional recurrence, we conducted a retrospective review of clinicopathologic factors. Methods: The clinicopathologic features of 103 patients with oral tongue SCC, in whom the local lesions were treated successfully by low-dose interstitial brachytherapy (LD-IBT), but who subsequently developed cervical lymph node metastases and were treated by salvage surgery, were reviewed. Results: In the patients who underwent surgical treatment at our hospital, 5-year disease-free survival and regional control rates were 69.3% and 85.3%, respectively. The clinicopathologic factors significantly associated with unfavorable disease-free survival were the presence of extracapsular spread (hazard ratio (HR) = 3.005, p = 0.045), multiple and large lymph nodes (HR = 2.850, p = 0.010 and HR = 3.112, p = 0.007, respectively), younger age (HR = 2.429, p = 0.048), and shorter interval from the LD-IBT to detection of neck metastasis (HR = 1.749, p = 0.013).

Deregulation of Snai2 is associated with metastasis and poor prognosis in tongue squamous cell carcinoma

The members of the Snail superfamily of zinc-finger transcription factors, including Snai1 and Snai2, are involved in essential biological processes, such as epithelial-mesenchymal transition (EMT). Although Snai1 has been investigated in a number of cancers, our knowledge on Snai2 and its role(s) in squamous cell carcinoma of oral tongue (SCCOT) is limited. In this study, we confirmed the previous observation that over-expression of Snai2 is a frequent event in SCCOT. We further demonstrated that Snai2 over-expression is associated with lymph node metastasis in two independent SCCOT patient cohorts (total n = 129). Statistical analysis revealed that Snai2 over-expression was correlated with reduced overall survival. Furthermore, over-expression of Snai2 was correlated with reduced E-cadherin expression and enhanced Vimentin expression, suggesting a functional role of Snai2 in EMT. These observations were confirmed in vitro, in which knockdown of Snai2 induced a switch from a mesenchymal-like morphology to an epithelial-like morphology in SCCOT cell lines, and suppressed the cell invasion and migration. In contrast, ectopic transfection of Snai2 led to enhanced cell invasion and migration. Furthermore, Snai2 knockdown attenuated TGFβ1-induced EMT in SCCOT cell lines. Taken together, these data suggest that Snai2 plays major roles in EMT and the progression of SCCOT and may serve as a therapeutic target for patients at risk of metastasis.

The characteristics and treatment results of squamous cell carcinomas of oral tongue

Results: The mean age of the patients with oral tongue SCC patients was 55 (19-85 years old). According to the T, N and pathologic stage , the patients were distributed from a higher to a lower incidence of cases, as follows: T2 (46.4%), T1 (37.9%), T4 (8.5%), and T3 (7 .1%); N0 (65%), N1 (20.7%), N2 (13.6%), and N3 (0.7%); and stage Ⅰ (31.4%), stage Ⅱ (25.7%), stage Ⅳ (22.2%), and stage Ⅲ (20.7%). Local and regional recurrence and distant metastasis was present in 13.6%, 5% and 4.2% of patients, respectively. The five-year survival rate was 72.2%, and the prognostic factors for oral tongue SCC included neck metastasis, pathologic stage of the disease, cell differentiation, treatment modality, neck d issection as part of the treatment plan, and neck node recurrence. Discussion: It is suggested that ipsilateral neck dissection or bilateral neck dissection should be selected as a treatment of tongue SCC p atients with advanced stage.

Lymphatic Mapping to Tailor Selective Lymphadenectomy in Squamous Cell Carcinoma of Oral Cavity

Objective: The purpose of this study was to determine the distribution of cervical lymph node metastases in the Squamous cell carcinoma of oral tongue and or floor of mouth; hence to improve the pretreatment evaluation of these patients. Study design: Descriptive study. Setting: Department of Oral and Maxillofacial Surgery, King Edward Medical University/ Mayo Hospital Lahore. From 1st July 2008 to 31st December 2009. Methods: This study was carried out on 50 consecutive patients who were having Squamous cell carcinoma of oral tongue and or floor of the mouth with T1 – T4 lesions. Results: Neck lymph node levels I and II were the most common sites of cervical lymph node metastases that was, 30%. Levels IV and V were involved very rarely. The overall metastases to cervical lymph node levels I – III combined was seen in 90% cases of oral tongue or floor of the mouth. Conclusion: The most common region for cervical lymph node metastases in Squamous Cell Carcinoma of oral tongue and floor of mouth is levels I – III in the ipsilateral neck, so based on pattern of metastases, supraomohyoid neck dissection for cN0 and functional neck dissection for cN+ necks are suggested. Key Words: Oral Squamous cell carcinoma (OSCC), cervical lymph node metastasis, cN0 (clinically lymph node negative), cN+ (clinically lymph node positive) (N1 – N3), pN+ (pathologically lymph node metastases found), elective neck dissection, occult metastasis, radical neck dissection (RND).

Genomic Differences between Smoking and Drinking Patients and Non-smoking and Non-drinking Patients with Oral Tongue Cancer

There has been a reported increase in the incidence of tongue cancer, especially in a much younger population that have not been exposed to the traditional risk factors -- cigarette smoking and alcohol use. The aim of this study is to identify the genomic differences between oral tongue cancers depending upon whether the patient had a history of smoking and/or drinking or not. Fresh frozen tissue from 12 patients with squamous cell carcinoma of oral tongue who underwent an operation between January 2004 and December 2006 were examined. DNA and high quality RNA was isolated from oral tongue tumors (cut to be greater than 80% tumor) and matched normal tissue from each of 6 patients with a drinking and smoking history and 6 younger patients without a drinking and smoking history was examined. Gene Expression Profiling (Affymetrix U133 Plus 2 arrays) and Array Comparative Genomic Hybridization (aCGH) using the Agilent platform were performed to analyze genome-wide alterations between these two distinct cohorts. Gene expression profiling analysis was performed. Using a paired t-test, there were a total of 5,767 transcripts with p <= 0.05 in the non-drinking and non-smoking patients, and 4,329 transcripts with p <= 0.05 in the drinking and smoking patients. We found that 7 genes were up-regulated and 6 genes were down-regulated in the drinking and smoking patients only; and that 6 genes were up-regulated and 10 genes were down-regulated in the non-drinking and smoking patients only. The aCGH data showed that 1p32.2-1p36.12; 3q26.31-3q27.2; 3q28; 4p15.33-4p13; 5p15.32-5p15.2; 7p12.1; 9q22.2-9q21.13; 9q34.2; 11q14.1-11q12.2; 16p13.2-16p12.1; 18p11.31; Xq12-Xq21.1 were regions of major difference between drinking/smoking and non-drinking/smoking patient samples. Genome-wide alterations are highly heterogeneous and vary significantly between the two patient groups. Thus, it is likely that different key genes and pathways are involved in oral tongue cancers related to tobacco and alcohol use and oral tongue cancers not related to tobacco and alcohol use. However, the results obtained need to be further validated in a larger number of oral tongue cancer samples.

Expression of EphA2 and VEGF in squamous cell carcinoma of the tongue: Correlation with the angiogenesis and clinical outcome

Eph-ephrin binding has been linked to tumor biology and VEGF has been reported to participate in the tumor angiogenesis regulated by Eph-ephrin. The present study was designed to evaluate the expression of EphA2 and VEGF in relation to angiogenesis and clinical outcome in squamous cell carcinoma of oral tongue. Immunohistochemical staining was used to determine the protein expression levels of EphA2 and VEGF in 59 surgically resected tongue carcinomas and 10 tumor-free mucosas. In all cases, microvessel density (MVD) was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. Both EphA2 and VEGF staining activities in squamous cell carcinoma of oral tongue were more significant than those in normal mucosa (P<0.01). MVD had significant correlations with EphA2 and VEGF expression (P<0.01). The EphA2, VEGF, and MVD were significantly correlated with tumor size, clinical stage, lymph invasion, recurrence, and distant metastasis (P<0.05). Multivariate analysis showed EphA2, VEGF expression, MVD, and clinical stage had an independent prognostic effect on overall survival. We conclude that the overexpression of EphA2 and VEGF are related to malignancy in squamous cell carcinoma of oral tongue. Clinical outcomes raised the possibility that the overexpression of those proteins might contribute to tumor angiogenesis and have prognostic value in tongue cancer.

O130 Squamous cell carcinoma of oral tongue in young adults: a different etiologic entity

O130 Squamous cell carcinoma of oral tongue in young adults: a different etiologic entity

P142 Expression of Ki-67 and endoglin (CD 105) proteins in stages I and II squamous cell carcinoma of oral tongue and floor of the mouth: association with demographic, clinical and histopathological factors prognostic analysis

P142 Expression of Ki-67 and endoglin (CD 105) proteins in stages I and II squamous cell carcinoma of oral tongue and floor of the mouth: association with demographic, clinical and histopathological factors prognostic analysis

Predictive value of histopathologic parameters in early squamous cell carcinoma of oral tongue

The clinical course of early squamous cell carcinoma of oral tongue (OTSCC) is unpredictable and various histopathologic parameters of the primary tumour have been suggested as prognostic factors to be used in clinical decision-making. We reviewed clinicopathologic data of 73 patients diagnosed with Stage I-II OTSCC. Predictive value of pathological T-stage, depth of infiltration, grade, and mode of invasion with respect to local recurrences, occult cervical metastases, and disease specific survival (DSS) was analysed. Depth of infiltration and pT-stage significantly predicted occult nodal disease, while only pT-stage predicted local recurrence. Specific cut-off value for depth of infiltration separating high-risk and low-risk patients was not found. Significant correlations between the histopathologic parameters and DSS were not found. We conclude that depth of infiltration predicted occult nodal disease but its value in clinical decision-making is limited because of poor specificity when using a cut-off value that offers reasonable sensitivity for finding the patients with occult nodal disease. The risk for occult metastases and local recurrence was high in patients with pT2 tumours.