Possible role of ALDH1 and CD44 in lip carcinogenesis.

BACKGROUND: Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Possible role of ALDH1 and CD44 in lip carcinogenesis

Abstract Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

Differential diagnoses of solitary and multiple pigmented lesions of the oral mucosa: Evaluation of 905 specimens submitted to histopathological examination.

BACKGROUND: The aim was to analyze the frequency, clinical and demographic features of solitary and multiple/diffuse oral pigmented lesions submitted to histopathological examination, and to summarize the features that guide the clinical differential diagnosis. METHODS: Clinical and demographic data were retrieved from biopsy records and descriptive statistics were performed. RESULTS: Nine hundred and five (0.51%) oral pigmented lesions were retrieved among 177 356 specimens, being 95.9% solitary and 4.1% multiple/diffuse lesions. Regardless the overlapping clinical presentation, age, site, association with amalgam restoration, and a nodular appearance may help in the clinical differential diagnosis of solitary oral pigmentations. Patient's habits, site, and systemic signs and symptoms are helpful in the clinical differential diagnosis of multiple/diffuse lesions. CONCLUSIONS: Oral pigmented lesions are a rare diagnosis in oral pathology and solitary lesions are more commonly submitted to biopsy. Some key features help in the differential diagnosis, though biopsy can be warranted in doubtful cases.

T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: Report of the First Case in the Mandible.

T-cell/histiocyte-rich large B-cell lymphoma (THRBCL) is an uncommon subtype of non-Hodgkin's lymphoma. It is a predominant nodal neoplasm; however, extranodal sites, such as the spleen, liver and bone marrow, can be involved at diagnosis. However, only one case of primary THRLBCL in the jaws have been reported. We herein describe a 29-year-old female patient who presented with a swelling of the right mandible that had grown rapidly over the previous 2 months. Periapical and panoramic radiographs showed a multilocular osteolytic lesion located in the mandibular periapical region of the canine and premolar teeth and molar region. Preoperative examination and incisional biopsy were performed. Immunohistochemistry was applied to confirm the diagnosis of THRBCL in the jaw. The treatment consisted of CHOP therapy and radiotherapy. After complete tumor remission following initial treatment, additional sites of the disease appeared in the lung, abdomen and long bones. The patient died within 2 months. THRLBCL is an uncommon and aggressive malignant neoplasm that can involve the jaws, mimicking a periapical disease.

Subcellular localization and expression of E-cadherin and SNAIL are relevant since early stages of oral carcinogenesis.

The biological process of epithelial-to-mesenchymal transition (EMT) has been studied in oral squamous cell carcinoma (OSCC) metastasis, but it is rarely evaluated at several stages of oral carcinogenesis. This study aimed to analyze the presence of SNAIL and E-cadherin proteins, markers of EMT, in the development and progression of OSCC, evaluating excised specimens of potentially malignant lesions (oral leukoplakia with and without dysplasia-OL and OLD, respectively), tumor tissues (OSCC), metastatic lymph nodes (LN), and normal oral mucosa (NOM) by immunohistochemistry, considering subcellular localization. Additionally, SNAIL and E-cadherin transcripts were evaluated in vitro by qPCR, using SCC-9 cell line in comparison to human keratinocytes (HPEC). There was a significant increase in nuclear expression of SNAIL from NOM to OLD followed by a noticeable decrease in nuclear expression accompanied by increased cytoplasmic expression in OSCC (p<0.05). The E-cadherin cytoplasmic expression was remarkable and statistically significant higher in OSCC and LN, both compared to NOM (p< 0.0001), OL (p<0.01) and OLD (p< 0.0001 and p<0.001, respectively). In vitro, E-cadherin and SNAIL transcripts were lower in SCC-9 compared to HPEC cells, although only the decrease of E-cadherin was statistically significant (p<0.05). Regarding the association of E-cadherin and SNAIL expression with the clinical findings, the analysis revealed an association between the cytoplasmic expression of SNAIL and the invasion pattern (p=0.05) in OSCC. The increased nuclear SNAIL expression may be characteristic of OLD, and the presence of E-cadherin in cell cytoplasm a marker of transformation to malignancy of potentially malignant oral leukoplakias into OSCC.

Immunohistochemical analysis of neutrophils, interleukin-17, matrix metalloproteinase-9, and neoformed vessels in oral squamous cell carcinoma.

BACKGROUND: Tumor-associated neutrophils (TAN), matrix metalloproteinase-9 (MMP-9), interleukin-17 (IL-17), and angiogenesis have been proposed as prognostic biomarkers of malignant tumors. The purpose of this study was to investigate these inflammatory markers as prognostic factors for oral squamous cell carcinoma (OSCC). METHODS: Specimens of OSCC (n = 30), healthy oral mucosa (negative control, n = 10), oral leukoplakia (n = 10), and apical granuloma with abscess (positive inflammatory controls, n = 10) were immunostained for CD66b (neutrophils), MMP-9, IL-17, and CD105 (neoformed microvessels). Semiquantitative (IL-17) and quantitative (CD66b, IL-17, MMP-9, and CD105) analyses were performed. Clinical information (TNM stage, metastasis, recurrence, and survival) and tumor histological grade were also obtained. RESULTS: Positivity for TAN, MMP-9, IL-17, and CD105 was higher in OSCC than in the negative control (P < 0.05) and oral leukoplakia, but similar to the positive inflammatory control. Coincident high counts of inflammatory markers (CD66b, MMP-9, IL-17, and CD105) were associated with lymph node metastasis of OSCC. Associations between high numbers of neoformed microvessels and advanced clinical stage and a higher degree of malignancy were also demonstrated. CONCLUSIONS: Combined positivity for TAN, MMP-9, IL-17, and CD105 appears to be associated with the metastasis-prone phenotype of OSCC.

Tratamento de cisto radicular de grande extensão: relato de caso clínico / Treatment of radicular cyst of extension: case report

Objetivo: Relatar o caso clínico de um cisto radicular extenso em maxila. Relato do caso: Paciente do sexo masculino, feoderma, 28 anos de idade, compareceu ao serviço de estomatologia queixando-se de "uma bolha no dente". O paciente relatou evolução da lesão há 15 dias e ter sido submetido a um tratamento endodôntico prévio no dente 21. No exame físico intraoral observou-se um discreto aumento de volume em palato anterior na região do dente 21. Os dentes ântero superiores responderam negativamente ao teste de vitalidade pulpar (TVP). A radiografia panorâmica e tomografia computadorizada odontológica revelaram uma imagem hipodensa expansiva unilocular, estendendo- -se da região do dente 16 até do dente 25, com limites parcialmente definidos e rechaçamento do soalho do seio maxilar direito e da cavidade nasal. Tratamento: Foi realizada biópsia incisional sendo o resultado do exame anatomopatológico sugestivo de um cisto radicular. A abordagem terapêutica inicial foi o tratamento endodôntico dos dentes que apresentaram necrose pulpar preconizando a utilização do hidróxido de cálcio como medicação intracanal. Posteriormente ao tratamento endodôntico foi feita a marsupialização da lesão objetivando a descompressão cística. Após 3 meses de descompressão cirúrgica novos exames imaginológicos revelaram uma pequena regressão da lesão, no entanto, não satisfatória. Optou-se por realizar a curetagem da lesão sob anestesia geral. Confirmou-se novamente o diagnóstico de cisto radicular. Conclusão: Atualmente, 18 meses após a cirurgia, novos exames radiográficos demonstraram o processo de neoformação óssea no local da lesão.

Objective: To present the case of a large radicular cyst in the maxilla. Case report: Male patient, feoderma, 28 years old, attended the stomatology service complaining of "a bubble in the tooth." The patient reported the evolution of the injury for 15 days and has undergone previous endodontic treatment on the tooth 21. In intraoral physical examination it was observed a mild increase in the volume on anterior palate in the tooth 21 region. The anterior superior teeth responded negatively the pulp sensitivity test (PST). The panoramic radiography and dental CT scan revealed a hypodense image expansive unilocular extending from the region of the tooth 16 to tooth 25 with partially defined limits and move away of the right maxillary sinus floor and the nasal cavity. Treatment: Incisional biopsy was performed and the result of the pathological examination suggested a radicular cyst. The initial therapeutic approach had been the endodontic treatment of teeth presented pulp necrosis prioritizing the use of calcium hydroxide as intracanal dressing. Histopathological analysis showed a cystic lesion of inflammatory origin. After the endodontic treatment was made marsupialization of the lesion, aiming the cystic decompression. After 3 months of surgical decompression new imaging examination revealed a small regression of the lesion, however, is not satisfactory. We chose to realize curettage of the lesion under general anesthesia, reconfirming the diagnosis of radicular cyst. Conclusion: Currently, 10 months after surgery, new radiographs demonstrated the process of bone formation at the site of injury.

A multicenter study of malignant oral and maxillofacial lesions in children and adolescents.

OBJECTIVES: To investigate the frequency of malignant oral and maxillofacial lesions among children and adolescents from representative geographic regions of Brazil. MATERIALS AND METHODS: A retrospective study was conducted on biopsies obtained from 1990 to 2016 at six Brazilian oral and maxillofacial pathology referral centers. A total of 85,105 biopsy specimens from children and adolescents were analyzed. Gender, age, anatomical location, symptomatology and histopathological diagnosis were evaluated. Data were analyzed using descriptive statistical methods. RESULTS: Fifty-eight (0.06%) malignant oral and maxillofacial lesions were diagnosed in children (19%) and adolescents (81%). The lesions were more frequent among females (60.3%) and adolescents. The most prevalent lesions were mucoepidermoid carcinomas (22.4%), osteosarcomas (13.8%), squamous cell carcinomas (12.1%), and Burkitt's lymphomas (12.1%). The most commonly affected sites were the palate (19%), mandible (13.8%), and maxilla (13.8%). Almost half the patients were asymptomatic. CONCLUSION: Pediatric oral and maxillofacial malignant lesions were infrequent and showed wide diversity, with a prevalence of mucoepidermoid carcinomas. Analysis of malignant lesions in children and adolescents helps pediatric dentists and oncologists to obtain a better understanding of such lesions and to reduce the time for diagnosis, with a consequent improvement of prognosis.

Overexpression of immunomodulatory mediators in oral precancerous lesions.

Human leukocyte antigen (HLA) G and E, programmed cell death 1 ligand 1 (PD-L1), IL-10 and TGF-ß are proteins involved in failure of the antitumor immune response. We investigated the expression of these immunomodulatory mediators in oral precancerous lesions (oral leukoplakia-OL; n=80) and whether these molecules were related to the risk of malignant transformation. Samples of normal mucosa (n=20) and oral squamous cells carcinoma (OSCC, n=20) were included as controls. Tissue and saliva samples were analyzed by immunohistochemistry and ELISA respectively. Fifteen OL samples showed severe dysplasia (18.7%) and 40 samples (50%) presented combined high Ki-67/p53. Irrespective of the degree of epithelial dysplasia and the proliferation/apoptosis index of OL, the expression of HLA-G, -E, PD-L1, IL-10, TGF-ß2 and -ß3 was higher to control (P<0.05) and similar to OSCC (P>0.05). The number of granzyme B+ cells in OL was similar to control (P=0.28) and lower compared to OSCC (P<0.01). Salivary concentrations of sHLA-G, IL-10 and TGF-ß did not allow for a distinction between OL and healthy individuals. Overexpression of immunosuppressive mediators in the OL reflects the immune evasion potential of this lesion, which is apparently independent of at cytological and proliferation/apoptosis status.

Inflammatory response of human dental pulp to at-home and in-office tooth bleaching

ABSTRACT Tooth bleaching is a technique of choice to obtain a harmonious smile, but bleaching agents may damage the dental pulp. Objective: This study evaluated the inflammatory responses of human dental pulp after the use of two bleaching techniques. Material and Methods: Pulp samples were collected from human third molars extracted for orthodontic reasons and divided into three groups: control - no tooth bleaching (CG) (n=7); at-home bleaching with 15% carbamide peroxide (AH) (n = 10), and in-office bleaching with 38% hydrogen peroxide (IO) (n=12). Pulps were removed and stained with hematoxylin-eosin for microscopic analysis of inflammation intensity, collagen degradation, and pulp tissue organization. Immunohistochemistry was used to detect mast cells (tryptase+), blood vessels (CD31+), and macrophages (CD68+). Chi-square, Kruskal-Wallis, and Mann Whitney tests were used for statistical analysis. The level of significance was set at p<.05. Results: The inflammation intensity and the number of macrophages were significantly greater in IO than in AH and CG (p<0.05). The results of CD31+ (blood vessels per mm2) were similar in CG (61.39±20.03), AH (52.29±27.62), and IO (57.43±8.69) groups (p>0.05). No mast cells were found in the pulp samples analyzed. Conclusion: In-office bleaching with 38% hydrogen peroxide resulted in more intense inflammation, higher macrophages migration, and greater pulp damage then at-home bleaching with 15% carbamide peroxide, however, these bleaching techniques did not induce migration of mast cells and increased the number of blood vessels.

Overexpression of immunosuppressive cytokines is associated with poorer clinical stage of oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to evaluate the expression of IL-10 and TGF-ß2 in oral squamous cell carcinoma (OSCC) and its relationship with prognostic clinical and microscopic parameters. DESIGN: Immunohistochemistry was used to assess the expression of IL-10 and TGF-ß2 in OSCC samples from 43 patients who had undergone surgical excision and neck dissection. Metastatic lymph nodes were included in the study (n=23). Samples of healthy oral mucosa (n=20) were used as controls. The sections were evaluated using a semi-quantitative method in conjunction with staining intensity. RESULTS: Our findings showed that the expression of IL-10 and TGF-ß2 by neoplastic and stromal cells was high in most of the OSCC samples (>70% of samples), especially when compared to the controls (≅10% of samples) (P<0.05). OSCC neoplastic cells in cervical lymph nodes were also positive for IL-10 and TGF-ß2. An association between high expression of IL-10 by neoplastic cells and advanced clinical stage (T3-T4) was verified (P=0.02). Although not statistically significant, the expression of TGF-ß2 was also augmented in advanced stage tumours. CONCLUSIONS: These data suggest that the ability of OSCC neoplastic cells to secrete immunosuppressive cytokines could contribute to clinical progression by maintaining a microenvironment conducive to evasion and tumour proliferation.

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

BACKGROUND: There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. METHODS: Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). RESULTS: The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). CONCLUSION: There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm.

Immune response in cervical lymph nodes from patients with primary oral squamous cell carcinoma.

BACKGROUND: Deficient immune response in the cervical lymph nodes of patients with head and neck squamous cell carcinoma may contribute to dissemination of metastatic neoplastic cells. This study evaluates the immune response in cervical lymph nodes from patients with primary oral cavity squamous cell carcinoma (OCSCC). METHODS: The density of immature (CD1a(+)) and mature (CD83(+)) dendritic cells (DCs), cytotoxic T lymphocytes CD8(+) /perforin(+) (CTLs), and Foxp3(+) regulatory T (Tregs) cells in the lymph nodes of patients with OCSCC without cervical lymph node metastases (LN1) (negative) (n = 10) were identified through immunohistochemistry. From patients with cervical lymph node metastases, samples were obtained of lymph nodes both with (LM2) (positive) (n = 10) and without (LN2) (negative) (n = 10) metastases. RESULTS: The results demonstrated that the number of CD1a(+) and Foxp3(+) cells was significantly higher in the LM2 group than in either the LN1 or the LN2 group. In addition, the number of CD8(+) /perforin(+) and CD83(+) cells was significantly lower in the LM2 group than in the other groups. CONCLUSION: The results of this study demonstrate a higher density of immature DCs and Tregs cells and a lower density of mature DCs and activated CTLs in metastatic than in non-metastatic lymph nodes. These findings might indicate an immunosuppressive microenvironment, which could be involved in the spread of neoplastic cells to cervical lymph nodes.

Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma.

OBJECTIVE: To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. MATERIALS AND METHODS: The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-ß) cytokines. The level required for statistical significance was defined as p<0.05. RESULTS: The data showed a predominance of M2 phenotype (high percentage of IL-10(+)TGF-ß(+)) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-ß was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFß and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). CONCLUSION: A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-ß production, and consequently greater lymph node involvement and reduced patient survival time.

High-grade primary leiomyosarcoma in the mandible: diagnosis and treatment.

BACKGROUND: Leiomyosarcoma is a malignant tumor that originates in smooth muscle cells and is rarely found in the oral cavity. We present a case of high-grade primary leiomyosarcoma in the mandible and discuss the diagnosis process. METHODS: The patient was a 64-year-old white man who had a slight increase in volume in the left-side mandible with a radiolucent osteolytic image with the destruction of the mandibular cortex. Incisional biopsy and preoperative examination were performed, including cone beam CT and examination by immunohistochemistry that defined the histologic diagnosis of leiomyosarcoma. The patient underwent reconstruction with an osteocutaneous flap with microvascular anastomosis. RESULTS: Two years after the surgery, there was no sign of recurrence of the lesion. CONCLUSION: The use of cone beam CT to define the limits of the lesion and the immunohistochemical findings were essential to establish the treatment plan.

Midkine expression in oral squamous cell carcinoma and leukoplakia.

BACKGROUND: Midkine (MK), a 13-kDa heparin-binding growth factor, is overexpressed in various human cancers. However, its role in the development and progression of oral cavity squamous cell carcinoma (OCSCC) is still unclear. Thus, the aim of this study was to evaluate the expression of MK in samples of OCSCC, leukoplakia, and healthy oral mucosa (control). METHODS: Surgically excised specimens from patients with primary OCSCC (n = 28) were immunostained for MK, Ki-67, PCNA, p53, bcl-2, Bax, and CD31. Besides this, MK expression was also investigated in leukoplakia and normal oral mucosa. The relationship of MK(+) cells with clinical parameters (tumor location, tumor size, lymph node metastasis, and survival) and microscopic parameters (WHO histological grading, intensity of inflammation, proliferation index, apoptosis, and angiogenesis) was also evaluated. RESULTS: The results showed that MK expression was increased in OCSCC in relation to leukoplakia and normal mucosa. Furthermore, MK expression was increased in late-stage tumors (T3/T4) compared with early-stage lesions (T1/T2). MK-positive lesions also showed increased expression of the anti-apoptotic protein bcl-2. CONCLUSION: OCSCC, particularly late-stage tumors, exhibits increased MK expression, which may be involved in tumor progression via upregulation of anti-apoptotic genes, as shown by the augmented bcl-2 positivity in MK-positive tumors.

Distinct expression of perforin and granzyme B in lip and oral cavity squamous cell carcinoma.

BACKGROUND: Perforin and granzyme B (GB) are the main constituents of cytotoxic T-lymphocyte granules, and they have important roles in preventing the initiation and progression of cancer. METHODS: The aim of this study was to compare the expression of CD8(+) /perforin(+) double-staining and GB(+) cells, by immunohistochemistry, in primary oral cavity squamous cell carcinoma (OCSCC), lip squamous cell carcinoma (LSCC), non-dysplastic leukoplakia (LK), dysplastic LK, actinic cheilitis (AC), oral lichen planus (LP) and normal oral mucosa. RESULTS: Our results showed a higher expression of CD8(+) /perforin(+) and GB(+) cells in LSCC when compared with the samples of OCSCC, non-dysplastic and dysplastic LK, AC, oral LP and normal oral mucosa. In addition, increased CD8(+) /perforin(+) and GB(+) cell numbers were observed in all pre-malignant lesions (non-dysplastic LK, dysplastic LK, AC) when compared with the control. CONCLUSIONS: Perforin and GB proteins may contribute to antitumoural immunity, leading to the direct killing of tumour cells; however, it seems to occur more effectively in LSCC than OCSCC.

Distinctive clinical and microscopic features of squamous cell carcinoma of oral cavity and lip.

OBJECTIVE: This study was undertaken to gain insight into the distinctive features of squamous cell carcinoma of the lip (LSCC) and oral cavity (OCSCC). STUDY DESIGN: A total of 37 cases of LSCC and 54 of OCSCC were compared regarding clinical and microscopic findings. RESULTS: Predominance of head and neck TNM stages (HNTNM) T1-T2 in LSCC and T3-T4 in OCSCC was observed. A significant percentage (33.3%) of patients with OCSCC at HNTNM T1-T2 presented cervical lymph node metastasis and 18.75% died, whereas lymph node metastasis was absent and no patient died with LSCC at HNTNM T1-T2. LSCC demonstrated a higher number of cases with intense peritumoral inflammatory infiltrate compared with OCSCC. The analysis of the proliferative index demonstrated a significantly higher percentage of PCNA+ and Ki-67+ cells in OCSCC compared with LSCC. CONCLUSION: Our results suggest that OCSCC and LSCC demonstrate distinct clinical and microscopic characteristics that reflect different biologic behavior and prognosis.

The clinicopathological significance of the expression of Granzyme B in oral squamous cell carcinoma.

Granzyme B (GB) is a serine protease synthesized by activated cytotoxic T-lymphocytes and natural killer cells that induces neoplastic cells apoptosis. The expression of GB in the tumor microenvironment has been considered a favorable prognostic factor in several types of human cancers. Thus, the aim of this study was to evaluate the density of GB(+) cells in samples of oral cavity squamous cell carcinoma (OCSCC), as well as their relationship with clinical and microscopic parameters. GB expression was analyzed in 55 cases of OCSCC and metastatic and non-metastatic lymph nodes by means of immunohistochemistry. The high density of GB(+) cells demonstrated an association with the high percentage of Bax(+) and annexin V(+) neoplastic cells. In addition, the number of peritumoral GB(+) cells was significantly higher in the OCSCC group without lymph node metastasis, when compared with the metastatic OCSCC group. Moreover, patients with OCSCC with a high density of peritumoral GB(+) cells showed a longer survival time when compared with patients with a lower density of these cells. In lymph node tissues, the density of GB(+) cells was significantly higher in non-metastatic lymph nodes than in metastatic lymph nodes. Our findings suggest that the increased of expression of GB in the tumor microenvironment of OCSCC and in lymph nodes may have beneficial effect against neoplastic cells, contributing to apoptosis of these cells and increased survival of patients.