RESUMEN
BACKGROUND: Sun exposure may lead to actinic keratoses (AKs), field cancerization, and skin cancer. Effective treatment of AKs and field cancerization is important. Oral and topical retinoids can be used for this purpose. To compare clinical, histological, and immunohistochemical effects of oral and topical retinoid for AKs and field cancerization on face and upper limbs of immunocompetent patients, as well as the impact on quality of life, safety, and tolerability. METHODS: This study compared 10 mg/day oral isotretinoin (ISO) to 0.05% tretinoin cream (TRE) every other night, associated with sunscreen (SPF 60). Patients of both genders, aged 50-75 years, underwent cryotherapy with liquid nitrogen for AKs at baseline and after 120 days when they were randomized into two groups, TRE (n = 31) and ISO (n = 30), for 6 months. Outcome measures were: number of AKs, histological (thickness of stratum corneum and epithelium) and immunohistochemical parameters (p53, Bcl-2 and Bax), dermatology life quality index (DLQI), and adverse events. RESULTS: Both treatments reduced the number of AKs (around 28%), the thickness of stratum corneum, and expression of p53 and Bax. By contrast, the epithelium thickness and Bcl-2 expression increased. There was no difference in the outcomes between TRE and ISO. Both treatments improved quality of life and were well tolerated with minimal side effects. CONCLUSIONS: Retinoids are effective and safe for field cancerization. Classical treatments for field cancerization (imiquimod and ingenol mebutate) are used for a short period; retinoids may be a good choice to intercalate with them and can be used continuously.
Asunto(s)
Antineoplásicos/uso terapéutico , Dermatosis Facial/tratamiento farmacológico , Isotretinoína/uso terapéutico , Queratosis Actínica/tratamiento farmacológico , Tretinoina/uso terapéutico , Administración Cutánea , Administración Oral , Anciano , Antineoplásicos/administración & dosificación , Dermatosis Facial/metabolismo , Dermatosis Facial/patología , Femenino , Humanos , Inmunohistoquímica , Isotretinoína/administración & dosificación , Queratosis Actínica/metabolismo , Queratosis Actínica/patología , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Calidad de Vida , Crema para la Piel/uso terapéutico , Neoplasias Cutáneas/metabolismo , Tretinoina/administración & dosificación , Proteína p53 Supresora de Tumor/metabolismo , Extremidad Superior , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Actinic keratoses are benign intraepithelial skin neoplasms that develop in photoexposed areas and can progress to invasive carcinoma. They are seen frequently in dermatological practice, occurring in 5.1% of consultations. Ingenol mebutate (IM) was recently approved in Brazil as a topical therapy for field cancerization in actinic keratosis. OBJECTIVE: To evaluate the clearance rate and adverse events in the treatment of actinic keratoses with ingenol mebutate. METHODS: A longitudinal, prospective, non-randomized, interventional, open, single-center study was conducted. Patients with actinic keratoses applied ingenol mebutate on a 25cm2 area of the face and/or scalp for three consecutive days (0.015%) or on the forearm for two days (0.05%). RESULTS: 27 patients completed the protocol, of whom 13 on the face and/or scalp and 14 on the forearm. Complete clearance occurred in 53.8% in the first group and 42.8% in the second. Partial response was observed in 15.4% and 35.7%, respectively. The most common side effects were erythema, edema, desquamation, pruritus, and local erosion. STUDY LIMITATIONS: The study had a small sample and was not randomized, double-blind, placebo-controlled, or vehicle-controlled. CONCLUSION: Ingenol mebutate is well-tolerated for the treatment of actinic keratosis, with good patient adherence thanks to the short treatment period.
Asunto(s)
Diterpenos/uso terapéutico , Queratosis Actínica/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Diterpenos/efectos adversos , Diterpenos/farmacocinética , Método Doble Ciego , Femenino , Humanos , Queratosis Actínica/metabolismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Abstract: Background: Actinic keratoses are benign intraepithelial skin neoplasms that develop in photoexposed areas and can progress to invasive carcinoma. They are seen frequently in dermatological practice, occurring in 5.1% of consultations. Ingenol mebutate (IM) was recently approved in Brazil as a topical therapy for field cancerization in actinic keratosis. Objective: To evaluate the clearance rate and adverse events in the treatment of actinic keratoses with ingenol mebutate. Methods: A longitudinal, prospective, non-randomized, interventional, open, single-center study was conducted. Patients with actinic keratoses applied ingenol mebutate on a 25cm2 area of the face and/or scalp for three consecutive days (0.015%) or on the forearm for two days (0.05%). Results: 27 patients completed the protocol, of whom 13 on the face and/or scalp and 14 on the forearm. Complete clearance occurred in 53.8% in the first group and 42.8% in the second. Partial response was observed in 15.4% and 35.7%, respectively. The most common side effects were erythema, edema, desquamation, pruritus, and local erosion. Study limitations: The study had a small sample and was not randomized, double-blind, placebo-controlled, or vehicle-controlled. Conclusion: Ingenol mebutate is well-tolerated for the treatment of actinic keratosis, with good patient adherence thanks to the short treatment period.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Diterpenos/uso terapéutico , Queratosis Actínica/tratamiento farmacológico , Método Doble Ciego , Estudios Prospectivos , Estudios Longitudinales , Resultado del Tratamiento , Diterpenos/efectos adversos , Diterpenos/farmacocinética , Queratosis Actínica/metabolismoRESUMEN
BACKGROUND: Topical tretinoin cream is the gold standard treatment for skin ageing, particularly photoaging. The purpose of tretinoin peel was to obtain similar results, but in a shorter time, however, there have been few controlled trials on its effectiveness. OBJECTIVE: To compare efficacy and safety of tretinoin 0.05% cream and 5% as a peeling agent on photoaging and field cancerization of the forearms. METHODS: Clinical trial with therapeutic intervention, prospective, randomized (computer-generated randomization list), parallel, comparative (intrasubject) and evaluator-blinded (except for histology and immunohistochemistry), including 24 women (48 forearms) aged over 60 years who have not undergone hormone replacement and categorized as Fitzpatrick skin phototype II or III. The forearms of the participants were randomized for treatment with 0.05% tretinoin cream three nights a week, or 5% tretinoin peel every 2 weeks. The opinion of the participant, severity of photoaging, corneometry, profilometry, high-frequency ultrasound, histology (haematoxylin-eosin and Verhoeff stainings) and immunohistochemistry (p53, bcl-2, Ki67 and collagen I) were assessed. RESULTS: One participant dropped out. The mean photoaging score reduced 20% and the mean actinic keratosis (AK) count reduced 60% with no difference between treatments. Three efficacy parameters showed opposite effects between the tretinoin treatments (P < 0.05%): (i) thickness of the corneal layer decreased with 0.05% tretinoin and increased by 5%; (ii) dermis echogenicity increased by 0.05% and decreased by 5% and (iii) Ki67 expression increased by 0.05% and decreased by 5%. There was good tolerability for both regimens. CONCLUSION: Tretinoin as a cream 0.05% or peeling (5%) is safe and effective for the treatment of moderate photoaging and forearm field cancerization. The cream was superior in improving ultrasonographic parameters of ageing. Peeling was shown a superior performance in the stabilization of field cancerization.
Asunto(s)
Antineoplásicos/administración & dosificación , Quimioexfoliación , Queratosis Actínica/tratamiento farmacológico , Envejecimiento de la Piel/efectos de los fármacos , Crema para la Piel/administración & dosificación , Tretinoina/administración & dosificación , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Dermis/diagnóstico por imagen , Epidermis/diagnóstico por imagen , Femenino , Antebrazo , Humanos , Queratosis Actínica/metabolismo , Queratosis Actínica/patología , Antígeno Ki-67/metabolismo , Estudios Prospectivos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Método Simple Ciego , Envejecimiento de la Piel/patología , Crema para la Piel/efectos adversos , Fenómenos Fisiológicos de la Piel/efectos de los fármacos , Tretinoina/efectos adversos , Proteína p53 Supresora de Tumor/metabolismo , UltrasonografíaRESUMEN
BACKGROUND: Skin cancer represents the most common worldwide malignancy. Angiogenesis is an important factor in tumor growth and metastasis. Given these facts, the purpose of the current study was to compare the levels of angiogenic proteins in the context of the most common malignant and premalignant skin lesions. METHODS: Immunohistochemistry of CD31, HIF1A, VEGFR1 and VEGFR2 was performed in basal cell carcinoma (BCC), actinic keratosis (AK) and squamous cell carcinoma of the skin (SCCS). RESULTS: SCCS presented with increased levels of HIF1A, VEGFR1 and VEGFR2 in comparison to AK. In addition, SCCS also demonstrated increased levels of HIF1A to BCCLR or BCCHR. BCC presented with more vessels than AK. However, no correlation was observed among CD31, HIF1A, VEGFR1 and VEGFR2. CONCLUSIONS: SCCS presented with higher levels of HIF1A, VEGFR1 and VEGFR2, while BCC demonstrated an increased number of vessels in relation to AK. These data suggest that antiangiogenic therapy might be useful for skin cancer treatment.
Asunto(s)
Proteínas Angiogénicas/análisis , Carcinoma Basocelular/química , Carcinoma de Células Escamosas/química , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Queratosis Actínica/metabolismo , Neoplasias Cutáneas/química , Carcinoma Basocelular/irrigación sanguínea , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/patología , Humanos , Inmunohistoquímica , Queratosis Actínica/patología , Neovascularización Patológica , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Estudios Retrospectivos , Neoplasias Cutáneas/irrigación sanguínea , Neoplasias Cutáneas/patología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/análisis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisisRESUMEN
Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P < .05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC.
Asunto(s)
Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Queratosis Actínica/metabolismo , Metaloproteinasa 14 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Neoplasias Cutáneas/metabolismo , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Queratosis Actínica/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: The antimetabolite 5-fluorouracil (5-FU) is used for topical treatment of actinic keratosis. Overall improvement in the skin is also observed. Additionally, 5-FU was reported to be used for superficial peels. OBJECTIVES: To evaluate the efficacy and safety of 5% 5-FU cream compared with peels for photodamaged forearms. METHODS: This interventional, randomized, comparative, evaluator-blind study included 32 patients with severe photoaging of forearms. The regimens comprised either application of 5% 5-FU cream everyday for 4 weeks on 1 forearm and 4 weekly peels on the other. Efficacy assessment included: clinical photodamage scores, opinion of patients and investigators, and blind photographic evaluation by independent observers. Skin biopsies were performed for histologic and immunohistochemical analysis. Safety evaluation comprised observation of adverse events. RESULTS: Clinical and histologic findings confirmed the benefits of topical 5% 5-FU, in cream or peels, which improved skin appearance and decreased the dermal elastotic material. Immunohistochemistry showed reduced levels of epidermal p53 and increase in the level of procollagen I. Results were maintained after 6 months. Predictable adverse events occurred, with no differences between treatments. Patients reported better tolerability to peels. CONCLUSION: Five percent 5-FU cream or peels was safe and effective for the treatment of photodamaged forearms. Decreased epidermal p53 levels and new dermal collagen were confirmed.
Asunto(s)
Quimioexfoliación , Colágeno Tipo I/efectos de los fármacos , Fluorouracilo/administración & dosificación , Queratolíticos/administración & dosificación , Queratosis Actínica/tratamiento farmacológico , Crema para la Piel/administración & dosificación , Administración Cutánea , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Biopsia , Quimioexfoliación/métodos , Método Doble Ciego , Femenino , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Antebrazo/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Queratolíticos/uso terapéutico , Queratosis Actínica/metabolismo , Queratosis Actínica/patología , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Índice de Severidad de la Enfermedad , Envejecimiento de la Piel/efectos de los fármacos , Crema para la Piel/uso terapéutico , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: Since the use of laminin-5 as a marker of invasiveness has been proposed by several authors, our objective was to compare the expression of this protein in pseudocarcinomatous hyperplasia and squamous cell carcinoma (SCC). METHODS: Sixty-four paraffin-embedded skin biopsy samples with diagnosis of epidermal hyperplasia (non-pseudocarcinomatous), pseudocarcinomatous hyperplasia, actinic keratosis/carcinoma in situ, microinvasive and frankly invasive SCC were obtained for immunohistochemical study. RESULTS: Adjacent normal epithelium and epidermal hyperplasia (non-pseudocarcinomatous) showed no staining. In pseudocarcinomatous hyperplasia, laminin-5 was positive, at least focally, in 14 of 16 (87.5%) samples and was concentrated in peripheral cells of elongated rete pegs and in migrating cells in dermis. In samples of microinvasive carcinoma (n = 7), the expression was observed in all cases and was concentrated in the leading edge of the tumor. All cases (n = 21) of frankly invasive SCC showed cells expressing laminin-5, at least focally. Well-differentiated areas of the tumor presented a pattern of expression in peripheral cells of tumor nests while a diffuse pattern of expression was observed in less differentiated areas. CONCLUSION: We showed that cytoplasmic laminin-5 expression should not be used as a criterion of malignancy and is not useful in distinguishing pseudocarcinomatous hyperplasia from microinvasive and well-differentiated SCC.
Asunto(s)
Carcinoma de Células Escamosas/patología , Laminina/metabolismo , Neoplasias Cutáneas/patología , Piel/patología , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/metabolismo , Humanos , Hiperplasia/metabolismo , Hiperplasia/patología , Queratosis Actínica/metabolismo , Queratosis Actínica/patología , Invasividad Neoplásica , Piel/metabolismo , Neoplasias Cutáneas/metabolismoRESUMEN
FUNDAMENTOS: O câncer de pele é o mais frequente tipo de câncer humano e mostra aumento de sua incidência. Em muitos casos, antes do surgimento do carcinoma, instala-se uma lesão precursora, ceratose actínica, podendo evoluir para carcinoma espinocelular. Estudos buscam determinar os parâmetros com significado prognóstico na predição daqueles tumores que terão comportamento mais agressivo. OBJETIVO: Avaliar a expressão dos marcadores de proliferação celular (PCNA, Ki-67) e apoptose (p53, Bcl-2), em portadores de carcinoma espinocelular e ceratose actínica. MÉTODO: Foram estudadas amostras de 30 pacientes: sendo dez portadores do carcinoma espinocelular; dez de ceratose actínica e dez indivíduos livres de lesões submetidos à blefaroplastia. RESULTADOS: A proteína p53 foi expressa em todos os casos estudados, embora apresentassem padrões quantitativos diferentes. O Bcl-2 foi expresso em baixa intensidade. Em seis casos de ceratose actínica, nas peles de blefaroplastia, e negativo nos casos de carcinoma espinocelular. O PCNA exibiu expressão intensa, em todas as amostras. O Ki-67 apresentou expressão variável, nos casos de carcinoma e de ceratose, e negativo na pele de pálpebra. CONCLUSÃO: A expressão do Ki-67 e a não-expressão de Bcl-2, no grupo CEC, indica intensificação da atividade proliferativa. Ao passo que, a maior expressão de p53 e Bcl-2, no grupo CA, sugere imortalização celular.
BACKGROUND: Skin cancer is the most frequent type of human cancer and has shown an increase in its incidence. In many cases, before the onset of the carcinoma, there might be a precursor lesion - actinic keratosis, which can develop into squamous cell carcinoma. Studies have been carried out in order to etermine the parameters that have prognostic significance in predicting those tumors which have more aggressive behavior. OBJECTIVE: To evaluate the expression of markers of cell proliferation (PCNA, Ki-67) and apoptosis (p53,Bcl-2) in patients with squamous cell carcinoma and actinic keratosis. METHOD: We studied samples from 30 patients, ten patients of squamous cell carcinoma, ten with actinic keratosis and ten lesion-free samples from blepharoplasty. RESULTS: p53 protein was expressed in all cases with different quantitative patterns. Bcl-2 was expressed at low intensity in six cases of actinic keratosis in the skin from blepharoplasty and negative in cases of squamous cell carcinoma. PCNA showed intense expression in all samples. Ki-67 showed variable expression in cases of keratosis and carcinoma and negative in the skin from the eyelid. CONCLUSION: The high expression of Ki-67 associated with low expression of Bcl-2 indicates proliferation in the carcinoma group. Thus, expression of p53 and Bcl-2 in patients with actinic keratosis indicates cell immortalization.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoptosis , Proliferación Celular , Carcinoma de Células Escamosas/patología , Queratosis Actínica/patología , Neoplasias Cutáneas/patología , Biomarcadores/análisis , Transformación Celular Neoplásica , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/metabolismo , Queratosis Actínica/metabolismo , /análisis , /biosíntesis , Antígeno Nuclear de Célula en Proliferación/análisis , Antígeno Nuclear de Célula en Proliferación/biosíntesis , /análisis , /biosíntesis , Neoplasias Cutáneas/química , Neoplasias Cutáneas/metabolismo , /análisis , /biosíntesisRESUMEN
BACKGROUND: Actinic cheilitis (AC) is an oral pre-cancerous lesion that sometimes develops into lip squamous cell carcinoma (SCC). Syndecan-1, a transmembrane heparan sulfate proteoglycan, modulates cell-proliferation, adhesion, migration and angiogenesis. Malignant epithelial cells often down-regulate their own syndecan-1 production, and are capable of inducing aberrant syndecan-1 expression in stromal cells. The aim of this study was to evaluate the variations in syndecan-1 expression during lip carcinogenesis, in normal lip (NL), AC and well-differentiated lip SCC. METHODS: Biopsies of NL vermillion (n = 19), AC (n = 23) and lip SCC (n = 24) were stained immunohistochemically for syndecan-1. RESULTS: Syndecan-1 expression was significantly reduced in AC and lip SCC as compared to NL (P < 0.05), with a significant reduction in lip SCC as compared to AC (P < 0.0001). In lip SCC lesions, syndecan-1 expression at the epithelium overlying the tumor was increased when compared to the tumor itself (P < 0.03), but was significantly reduced as compared to AC and NL (P < 0.001). CONCLUSION: The results showed that epithelial syndecan-1 expression is reduced as lip carcinogenesis progresses (NL>AC>lip SCC), suggesting that syndecan-1 could be a useful marker of malignant transformation in the lip.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Queilitis/metabolismo , Queratosis Actínica/metabolismo , Neoplasias de los Labios/metabolismo , Sindecano-1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Queilitis/complicaciones , Queilitis/patología , Femenino , Humanos , Queratosis Actínica/complicaciones , Queratosis Actínica/patología , Labio/metabolismo , Labio/patología , Neoplasias de los Labios/patología , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
BACKGROUND: Skin cancer is the most frequent type of human cancer and has shown an increase in its incidence. In many cases, before the onset of the carcinoma, there might be a precursor lesion--actinic keratosis, which can develop into squamous cell carcinoma. Studies have been carried out in order to determine the parameters that have prognostic significance in predicting those tumors which have more aggressive behavior. OBJECTIVE: To evaluate the expression of markers of cell proliferation (PCNA, Ki-67) and apoptosis (p53,Bcl-2) in patients with squamous cell carcinoma and actinic keratosis. METHOD: We studied samples from 30 patients, ten patients of squamous cell carcinoma, ten with actinic keratosis and ten lesion-free samples from blepharoplasty. RESULTS: p53 protein was expressed in all cases with different quantitative patterns. Bcl-2 was expressed at low intensity in six cases of actinic keratosis in the skin from blepharoplasty and negative in cases of squamous cell carcinoma. PCNA showed intense expression in all samples. Ki-67 showed variable expression in cases of keratosis and carcinoma and negative in the skin from the eyelid. CONCLUSION: The high expression of Ki-67 associated with low expression of Bcl-2 indicates proliferation in the carcinoma group. Thus, expression of p53 and Bcl-2 in patients with actinic keratosis indicates cell immortalization.
Asunto(s)
Apoptosis , Carcinoma de Células Escamosas/patología , Proliferación Celular , Queratosis Actínica/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/metabolismo , Transformación Celular Neoplásica , Femenino , Humanos , Queratosis Actínica/metabolismo , Antígeno Ki-67/análisis , Antígeno Ki-67/biosíntesis , Masculino , Persona de Mediana Edad , Antígeno Nuclear de Célula en Proliferación/análisis , Antígeno Nuclear de Célula en Proliferación/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Neoplasias Cutáneas/química , Neoplasias Cutáneas/metabolismo , Proteína p53 Supresora de Tumor/análisis , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including oral cancers. Recent studies have shown that mast cell-derived protease tryptase can induce COX-2 expression by the cleavage of proteinase-activated receptor-2 (PAR-2). Actinic cheilitis (AC) is a premalignant form of lip cancer characterized by an increased density of tryptase-positive mast cells. To investigate the possible contribution of tryptase to COX-2 overexpression during early lip carcinogenesis, normal lip (n=24) and AC (n=45) biopsies were processed for COX-2, PAR-2 and tryptase detection, using RT-PCR and immunohistochemistry. Expression scores were obtained for each marker and tested for statistical significance using Mann-Whitney and Spearmann's correlation tests as well as multivariate logistic regression analysis. Increased epithelial co-expression of COX-2 and PAR-2, as well as, elevated subepithelial density of tryptase-positive mast cells were found in AC as compared to normal lip (P<0.001). COX-2 overexpression was found to be a significant predictor of AC (P<0.034, forward stepwise, Wald), and to be correlated with both tryptase-positive mast cells and PAR-2 expression (P<0.01). The results suggest that epithelial COX-2 overexpression is a key event in AC, which is associated with increased tryptase-positive mast cells and PAR-2. Therefore, tryptase may contribute to COX-2 up-regulation by epithelial PAR-2 activation during early lip carcinogenesis.