Squamous Cell Carcinoma Of Lower Lip Research Articles

Comparison of the histologic risk assessment model between lower lip and oral squamous cell carcinoma.

The histologic risk assessment (HRA) grading system was proposed as a practical measure to predict clinical outcome and its effectiveness has been shown in several studies. It has been suggested that the HRA model might exhibit differences among various oral subsites. The aim of the present study was to compare this system between squamous cell carcinomas (SCCs) of the lower lip (LL) and oral cavity. All primary SCCs located in the LL and oral cavity were retrieved and graded using the HRA model. Data regarding risk score (RS), perineural invasion (PNI), lymphocytic infiltration (LI) and worst pattern of invasion (WPOI) were compared between LL and oral SCCs using χ2 analysis (P<0.05). There were a total of 33 LLSCCs, of which 15, 8 and 10 were categorized as low-risk (RS=0), intermediate-risk (RS=1-2) and high-risk (RS≥3) tumors, respectively. Corresponding values in the 48 oral SCCs were 7, 15 and 26 cases. Significant differences in RS (P=0.00), LI (P=0.01) and WPOI (P=0.01) were observed between LL and oral tumors. The HRA model could be included among the various factors suggested to be different between lip and oral SCCs. Low-risk tumors were more prevalent in the lip which corroborates the less aggressive nature of these cancers. Considering the significantly higher LI in LL SCCs, inflammation may be regarded as an important factor in regulating the invasive behavior of these tumors.

Pattern of invasion in squamous cell carcinomas of the lower lip and oral cavity

BackgroundA number of factors may be responsible for the differences in the biologic behaviors of oral and lower lip squamous cell carcinomas (SCCs). Immunohistochemical invasion profiles have been used to detect invasion patterns like epithelial-mesenchymal-transition (EMT) and collective-cell-invasion (CCI), which have not been investigated in lower lip neoplasms. The aim of the present study was to compare the invasive phenotypes of SCCs of the lower lip and oral cavity. MethodA total of 44 OSCCs and 37 lower lip SCCs were immunostained with E-Cadherin, N-Cadherin, and podoplanin. Based on their expression patterns, tumors were allocated to EMT, CCI or non-EMT/non-CCI categories. ResultsNone of the oral SCCs showed EMT; while 5 lower lip SCCs demonstrated this phenotype. CCI was observed in 12 oral SCCs and 4 lower lip SCCs. The third group included 32 and 28 cases of oral and lower lip tumors, respectively. A significant difference in invasive phenotype was found between the two locations (P=0.009). ConclusionOral cavity and lip tumors differ in various aspects and according to our results; the pattern of invasion may be added to these features. Between the two major invasion patterns, EMT was more prevalent in lip tumors while CCI was observed more commonly in oral neoplasms. The significance of the different expression patterns of the non-EMT/non-CCI category requires further investigation.

One Stage Aesthetic and Functional Reconstruction of Major Lower Lip Defects.

Multiple techniques have been used for reconstruction of large defects of the lower lip. However, some complications, such as microstomia, distortion of oral commissure, lip functional problems, and sensory loss might occur with these techniques. The aim of this work is to evaluate a new method of reconstruction of large lower lip defects after excision of squamous cell carcinoma. Eighteen patients with lower lip squamous cell carcinomas were managed with this new technique of reconstruction using dermal fat flap, mucobuccal flap, and muscle transfer after excision of the tumor with 1-cm safety margin on both sides. The functional and aesthetic assessments were performed at least 6 months after surgery, and the results were compared statistically with a control group. Of the 18 patients, sensibility was normal in 16 (89%) and complete competence was determined in all cases (100%). In 17 patients (94%), complete and symmetric pouting and mouth-opening movements were ensured. Interlabial measurements would be better in all patients. Nasolabial asymmetry was detected in 1 patient (6%) and apparent mentolabial scar tissue was detected in 2 patients (11%). The new vermilion was of equal width to the upper lip vermilion in 15 patients (83%). Based on our results, this technique could be considered a good choice for repair of major lip defects. In addition, using this technique will give good aesthetic and functional results.

Multinucleated giant cell reaction in lower lip squamous cell carcinoma: a clinical, morphological, and immunohistochemical study.

Multinucleated giant cell (MGC) reactions have been identified in several malignancies, but their frequency and significance in lower lip squamous cell carcinoma (SCC) are not established. This study evaluated the MGC reactions and their association with clinicopathological parameters in lower lip SCCs. The polarization profile of these cells (M1 or M2 macrophages) was also assessed. The presence and distribution of MGC reactions in high-power fields (400×) were evaluated in hematoxylin/eosin-stained histological sections of 91 lower lip SCCs. The histopathological grade of malignancy was evaluated using two grading systems (World Health Organization [WHO] and Malignancy Grading of the Deep Invasive Margins). The histiocytic nature (CD68) and polarization profile (M1-HLA-DR+ or M2-CD163+) of MGCs were evaluated by immunohistochemistry. Multinucleated giant cell reaction was identified in 36 (39.6%) cases, and its frequency was 3.3 times higher in well/moderately differentiated tumors than in poorly differentiated tumors (WHO grading system) (P = 0.006). For Malignancy Grading of the Deep Invasive Margins, the frequency was 2.03 times higher in highly/moderately keratinized tumors than in tumors with minimal/no keratinization (P = 0.012). No significant associations were observed between the presence/distribution of MGCs and clinical parameters (tumor size, lymph node metastasis, distant metastasis, and clinical stage) (P > 0.05). All MGCs were positive for CD68 and there was a predominance of HLA-DR+ over CD163+ MGCs (P = 0.031). Multinucleated giant cell reactions may not be involved in tumor progression in lower lip SCCs. In this microenvironment, MGCs tend to exhibit a predominantly M1 phenotype and may represent a foreign body reaction to SCC keratin pearls.

Lower lip squamous cell carcinoma in patients with photosensitive disorders: Analysis of cases treated at the Brazilian National Cancer Institute (INCA) from 1999 to 2012.

BackgroundLower lip squamous cell carcinoma (LLSCC) is a common malignancy of the head and neck, being mainly a consequence of a chronic exposure to ultraviolet (UV) light solar radiation. Here, we evaluated the clinicopathological profile of patients with photosensitive disorders (xeroderma pigmentosum, lupus erythematosus and albinism) that developed LLSCC.Material and MethodsData from patients who had a diagnosed LLSCC with a prior xeroderma pigmentosum, lupus erythematosus or albinism diagnosis that were treated at INCA from 1999 to 2012 were collected from patients’ medical records (n=16). The control group was composed of 68 patients with LLSCC without a medical history of photosensitivity. The clinicopathological data of this study population were collected and the association between these variables was analyzed by Fisher’s exact test. Survival curves were constructed using the Kaplan–Meier method and compared by log-rank test. All statistical analyses were performed using SPSS statistics package.ResultsThe mean age of patients in the photosensitive and non-photosensitive groups was 42 years and 67 years, respectively (p<0.0001). A previous history of malignant diseases was more common in the photosensitive group (p=0.001). In both groups, most tumors showed a pathological stage I/II disease. Overall and cancer-specific survival were not statistically different. However, disease-free interval showed a significant difference (p=0.01) between the photosensitive and non-photosensitive patients.ConclusionsPhotosensitive patients presented LLSCC at earlier age but it usually was not the primary tumor in these patients. Furthermore, a more aggressive pathological behavior was not seen when compared with tumors from non-photosensitive patients. The disease-free interval was lower in photosensitive patients, as expected. Key words:Lip cancer, Xeroderma Pigmentosum, Albinism, Lupus erythematosus.

Immunohistochemical Analysis of Natural Killer Cells and CD8+ T Lymphocytes in Lower Lip Squamous Cell Carcinoma

Immunohistochemical Analysis of Natural Killer Cells and CD8+ T Lymphocytes in Lower Lip Squamous Cell Carcinoma

Immunoexpression of VEGFR-3, but not the immunoexpression of VEGF-C or lymphatic density, is correlated with metastasis in lower lip squamous cell carcinoma

The purpose of this study was to evaluate the immunoexpression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3) and their correlation with intratumoural lymphatic density (ILD) and peritumoural lymphatic density (PLD) in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). Twenty-five LLSCC with regional nodal metastasis and 25 LLSCC without metastasis were selected. The percentages of VEGF-C and VEGFR-3 staining in each tumour core and at the deep invasive front were assessed. PLD and ILD were determined using anti-podoplanin antibody. Immunohistochemical findings were correlated with nodal metastasis, clinical staging, local recurrence, clinical outcome, and histological grade. Cytoplasmic immunoexpression of VEGFR-3 in the tumour core was associated with metastasis (P=0.009), patient death (P=0.008), and histological grade (P<0.005). PLD, ILD, and VEGF-C expression showed no significant associations with clinicopathological parameters (P>0.05). PLD and ILD were not significantly correlated with the immunoexpression of VEGF-C or VEGFR-3 (P>0.05). There was a significant positive correlation between PLD and ILD (P=0.004), and between cytoplasmic immunoreactivity of VEGF-C and VEGFR-3 (P=0.011). These results suggest an important role for VEGFR-3 in the progression of LLSCC, and highlight the possible influence of its expression on the prognosis of these tumours. ILD and PLD may not be associated with lymph node metastasis in LLSCC.

The role of suprahyoid neck dissection in the treatment of squamous cell carcinoma of the lower lip: 20 years' experience at a Tertiary Center.

To evaluate the efficacy of L1-2ND in the management of the lower lip squamous cell carcinoma and to achieve the highest cure rates with adequate neck dissection. A retrospective review was completed on patients treated between 1994 and 2014. The case histories of 184 patients who were treated with surgical excision of the primary tumor along with neck dissection, and 24 patients who were treated only with surgical excision without neck dissection at another center, were studied. All patients were followed up for evidence of recurrent disease. In 208 patients (193 men, 15 women) with a mean age of 51 years, 12 were N1, 3 were N2, and 169 were N0; 24 patients had undergone operation at another center without neck dissection. Lymph node metastases were present in 34 patients (18.4%) with dissected necks and occult metastases were detected in 19 patients with clinically N0 necks (11.2%). The median follow-up of each patient was 28 months. Only 1 patient developed neck recurrence, and there was no local recurrence. The overall survival rate (OAS) of patients with clinical N0 disease who underwent neck dissection was 94.7%; the OAS of the patients who were not treated with neck dissection was 29.1%. Level 1-2 neck dissection (L1-2ND) is the treatment of choice for controlling neck disease in patients with lower lip carcinoma, and serves as a staging procedure to detect patients who require adjuvant therapy.

Early stage squamous cell carcinoma of the lower lip: predictive factors for recurrence

This study aimed to evaluate the effect of tumour thickness on other clinicopathological parameters in early stage lower lip squamous cell carcinoma. Forty-six consecutive patients with lower lip squamous cell carcinoma were included in the study. Demographic, clinical and pathological data were retrospectively collected. The mean follow-up period for all patients was 32.0 ± 18.9 months. Forty-four tumours were staged as T1 and two were T2. Twelve patients underwent neck dissection. Two patients presented with neck metastasis in the follow-up period. Four patients (8.7 per cent) had local recurrence. Correlation analysis revealed a significant relationship between microscopic tumour thickness and local tumour recurrence (r = 0.328, p = 0.045). Surgical margin control is important to prevent local recurrence, especially in thicker tumours. In addition, neck metastasis is rare in early stage lower lip squamous cell carcinoma. A 'wait and see' policy might be preferred in early stage T1 lower lip squamous cell carcinoma cases.

Correlation between cell cycle proteins and hMSH2 in actinic cheilitis and lip cancer.

This study aims to evaluate and verify the relationship between the immunoexpression of hMSH2, p53 and p21 in actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC) cases. Forty AC and 40 SCC cases were submitted to immunoperoxidase method and quantitatively analyzed. Expression was compared by Mann-Whitney test, Student t test or one-way ANOVA. To correlate the variables, Pearson's correlation coefficient was calculated. The expression of p53 and p21 showed no significant differences between histopathological grades of AC or lower lip SCC (p>0.05). Immunoexpression of p53 was higher in SCC than in AC (p<0.001), while p21 expression was more observed in AC when compared to SCC group (p=0.006). The AC group revealed an inverse correlation between p53 and hMSH2 expression (r=-0.30, p=0.006). Alterations in p53 and p21 expression suggest that these proteins are involved in lower lip carcinogenesis. Moreover, p53 and hMSH2 seem to be interrelated in early events of this process.

Immunohistochemical analysis of FoxP3+ regulatory T cells in lower lip squamous cell carcinomas.

The aim of this study was to determine the number of FoxP3+ regulatory T (Treg) cells in the microenvironment of lower lip squamous cell carcinomas (LLSCCs) and to correlate the findings with clinicopathological parameters (tumor size/extent, regional lymph node metastasis, clinical stage, and histopathological grade of malignancy). Fifty cases of LLSCC were selected. Lymphocytes exhibiting nuclear immunostaining for FoxP3 were quantified in 10 microscopic fields at the deep invasive front of LLSCCs. The results were analyzed statistically using the nonparametric Mann-Whitney test and Fisher's exact test. FoxP3+ lymphocytes were observed in all cases studied. The number of these cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (p > 0.05). Low-grade tumors contained a larger number of FoxP3+ lymphocytes than high-grade tumors (p = 0.019). Tumors with an intense inflammatory infiltrate exhibited a larger number of Treg cells (p = 0.035). On the other hand, the number of FoxP3+ lymphocytes was smaller in tumors arranged in small cell clusters (p = 0.003). No significant differences in the number of FoxP3+ lymphocytes were observed according to the degree of keratinization (p = 0.525) or nuclear pleomorphism (p = 0.343). The results suggest the participation of Treg cells in immune and inflammatory responses in the microenvironment of LLSCCs. These cells may play a more important role in early stages rather than in advanced stages of lip carcinogenesis.

下口唇の有棘細胞癌に対してDeltopectoral flapを用いて再建した1例

下口唇の有棘細胞癌に対してDeltopectoral flapを用いて再建した1例

CD1a+ and CD83+ Langerhans cells are reduced in lower lip squamous cell carcinoma.

Actinic cheilitis (AC) is a potentially malignant lesion diagnosed in the lip of patients chronically exposed to the sun that may give rise to a fully invasive lower lip squamous cell carcinoma (LLSCC). It is known that ultraviolet radiation causes dendritic cells (DCs) depletion in the epidermis, but the role of this cellular population in lip cancer progression remains uncertain. Therefore, this study investigated the distribution of DCs in normal, dysplastic and neoplastic tissues of the lower lip. Thirteen cases of lower lip mucocele, 42 of ACs and 21 of LLSCC were retrieved and original diagnoses confirmed by two oral pathologists, who further classified ACs as low- and high-risk lesions. Immunoreactions against CD1a and CD83 identified immature and mature DCs, respectively. Immature CD1a+ Langerhans cells (LCs) were significantly decreased in LLSCC when compared to morphologically normal (P < 0.009) and dysplastic epitheliums (P < 0.003), whereas mature CD83+ LCs were significantly decreased in LLSCC when compared to normal epithelium (P = 0.038). There was no significant difference between low- and high-risk ACs regarding CD1a+ and CD83+ LCs (P > 0.05), but ACs demonstrated a lower concentration of CD1a+ LCs than normal epithelium (P < 0.009). There was no significant difference in the distribution of CD1a+ and CD83+ interstitial dendritic cells (IDCs) in the connective tissue among the studied groups (P > 0.05). These results suggest that depletion of epithelial LCs, but not IDCs in the connective tissue, would represent an important step for lip cancer development.

Lymphangiogenesis and angiogenesis in oral cavity and lower lip squamous cell carcinoma

IntroductionTumors of the lip and oral cavity differ in various aspects; therefore a clarification of the distinctions among these sites may help to better understand the biologic behavior of neoplasms occurring in these locations. ObjectiveConsidering that angiogenesis and lymphangiogenesis are two major elements that can influence various aspects of tumor biology, we aimed to compare these factors between squamous cell carcinoma of the lower lip and oral cavity. MethodsA total of 84 primary squamous cell carcinomas including 45 oral and 39 lower lip tumors were selected and immunohistochemically stained with monoclonal antibody against D2-40 and CD105. Mean microvessel density was assessed in tumoral tissue, while lymphatic vessel density was calculated in both neoplastic tissue and invasion front. Data were statistically analyzed using t-test and p-values of <0.05 were considered significant. ResultsWe found a mean microvessel density±standard deviation of 31.94±18.9 in oral cavity and 27.54±20.8 in lower lip squamous cell carcinomas, with no significant difference (p=0.32). Mean lymphatic vessel density±standard deviation was 13.05±8.2 and 16.57±10.79 in of oral cavity and lower lip neoplastic tissue, respectively. The corresponding values were 9.94±5.59 and 12.50±7.8 in the invasive front. Significant differences were not observed in either of the lymphatic vessel density variables between the two sites. ConclusionAccording to our results, it seems that the search for additional factors other than those related to the vasculature should continue, to help clarify the differences in biologic behavior between lower lip and oral cavity squamous cell carcinomas.

A94: Immunohistochemical expression of Ki-67, CD34 and Podoplanin in hyperkeratosis and squamous cell carcinoma of the lower lip

Background Squamous cell carcinoma is the most common malignancy in the lower lip. Although lower lip squamous cell carcinoma is slow growing, up to 29% of tumors develop metastases to the cervical lymph nodes. Thus, identification of biological markers that could provide prognostic information about the invasive or metastatic potential of these lesions is important. It is known that angiogenesis, lymphangiogenesis and proliferation play an important role in tumor progression. Therefore, the goal of this study was to analyze the immunohistochemical expression of Ki-67, CD34 and Podoplanin in hyperkeratosis and in squamous cell carcinoma of the lower lip. It was intended to assess the possibility of using such markers as indicators of morphological aggressiveness of squamous cell carcinoma of the lower lip (LLSCC). Materials and methods Seventy-one cases of the lower lip lesions, obtained from the files of Novosibirsk Regional Oncology Center were selected for this study. The specimens were divided into three groups: a lower lip hyperkeratosis group consisting of 22 cases; LLSCC with keratinization consisting of 34 cases and LLSCC without keratinization consisting of 15 cases. To analyze angiogenesis, lymphangiogenesis and proliferation, we performed immunostains of the lower lip biopsy material for the CD34, vascular marker, Podoplanin, lymphatic-specific markers and Ki-67, marker of proliferation. Tissue samples were fixed in 10% neutral formalin, processed by standard histological techniques and embedded in paraffin. All steps of the immunohistochemical reaction were performed by using BENCHMARK/XT slide stainer (Ventana). The lymphatic and blood vessels volume density and Ki-67 cells numerical density were morphometrically analyzed in all groups and compared using the non-parametric Mann–Whitney test and the Wilcoxon signed rank test. A level of significance of 5% ( p Results All cases of a lower lip hyperkeratosis and LLSCC were positive for Ki-67, CD34 and Podoplanin. With respect to the pattern of staining, specimens exhibited a predominantly peripheral staining for CD34 and Podoplanin in inflammatory infiltrates and tumor sites. In contrast, staining for Ki-67 was predominantly central in inflammatory infiltrates and tumor sites in hyperkeratosis and LLSCC. When compared to lower lip hyperkeratosis, LLSCC (both with keratinization and without keratinization) showed a higher number of immunopositive Ki-67 cells (by 64% and 77%, respectively, p Conclusion This study has shown the greater development of blood and lymphatic vessels in LLSCC without keratinization in comparison with hyperkeratosis and LLSCC with keratinization, thus contributing to the development of metastasis.

Abstract 1065: RASSF- 1A methylation in squamous cell carcinoma of the lower lip using pyrosequencing technique

Abstract Background: Chronic exposure to UVB radiation can cause hypermethylation and silencing of the tumor suppressor gene RASSF-1A. The protein encoded by this gene has multiple important functions in cell cycle control. Objective: to investigate the clinical significance of the methylation profile of RASSF-1A and of its protein expression in lower lip squamous cell carcinoma (SCC). Methods: The demographic and clinical-pathological data of 87 patients with a confirmed diagnosis were collected from the medical records. DNA was extracted from paraffin-embedded tissue samples and treated with sodium bisulfite. 2ug of treated and intact DNA was submitted to PCR amplification using a specific primer targeting the RASSF-1A promoter segments 1 and 2. RASSF1A methylation was investigated by pyrosequencing; the complementary strand was synthesized automatically and the signal emitted during the reaction was detected with a camera and transformed into peaks on a pyrogram. Results: Lower lip SCC was more frequent in men than women, with a proportion of 2.4:1. The mean patient age was 63.3 years. Lymph node involvement was absent (N0) in 73 (83.1%) of cases and present (N+) in 14 (16.1%). In group N0, most patients (n = 49, 67.1%) were in an early clinical stage (CS I and II). Analysis of the methylation of RASSF1A_01 was possible in 29 of the SCC cases. Hypermethylation was observed in 15 (51.7%) cases, one (3.4%) of them being associated with metastasis to regional lymph nodes. Analysis of RASSF1A_02 was possible in 20 cases and hypermethylation was observed in only 9 (45.0%). No significant correlation was found between the clinical-pathological parameters (age, gender, clinical stage) and aberrant methylation of the promoter region studied (p&amp;gt;0.05). Conclusions: Hypermethylation of the two RASSF-1A segments studied was observed in approximately 50% of SCC cases, but was not correlated to clinicopathologic parameters. Citation Format: Estela Kaminagakura, Cláudia Coutinho-Camillo, Luciana Strieder, Danyel Perez, Fernando Soares, Kátia Oliveira, Luiz Paulo Kowalski. RASSF- 1A methylation in squamous cell carcinoma of the lower lip using pyrosequencing technique. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1065. doi:10.1158/1538-7445.AM2015-1065

Characterization of Tumor-Associated Macrophages Subpopulation M1 and Their Relationship With Clinicopathological Parameters in Lower Lip Squamous Cell Carcinomas

To analyze the presence of tumor-associated macrophages (TAMs), subpopulation M1, in lower lip squamous cell carcinoma (LLSCC) by immunohistochemistry and to evaluate the possible association of this cell subtype with clinicopathological features of the tumor.

Immunoexpression of hMSH2, p53, and p21 in Actinic Cheilitis and Lower Lip Squamous Cell Carcinoma

To evaluate and associate the immunoexpression of hMSH2, p53, and p21 in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC).

Immunoexpression of Tumor-Associated Macrophages Subpopulation M2 in Lower Lip Squamous Cell Carcinomas

Immunoexpression of Tumor-Associated Macrophages Subpopulation M2 in Lower Lip Squamous Cell Carcinomas

Morphological Study of the Osteoclast-Like Giant Cell Reaction in Lower Lip Squamous Cell Carcinoma

Morphological Study of the Osteoclast-Like Giant Cell Reaction in Lower Lip Squamous Cell Carcinoma