Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: -0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation.

CXCL12 chemokine and CXCR4 receptor: association with susceptibility and prognostic markers in triple negative breast cancer.

CXCL12/CXCR4 signaling has been implicated in breast carcinogenesis, and genetic polymorphisms in these molecules have been associated with different types of cancer. The present study analyzed genetic polymorphisms in CXCL12 (rs1801157, G > A) and CXCR4 (rs2228014, C > T) and CXCR4 immunostaining in tumor tissues from patients with triple negative breast cancer (TNBC) aiming to evaluate their possible role in its' susceptibility and prognosis. Genetic polymorphisms were analyzed in 59 TNBC patients and 150 control women; age-adjusted logistic regression showed no association when variants were considered in isolation; however, a statistically significant interaction was noted for heterozygosis for both allelic variants increasing the odds for TNBC (CXCL12-GA by CXCR4-CT: OR 7.23; 95% CI 1.15-45.41; p = 0.035). CXCL12 polymorphism was correlated negatively with proliferation index (Ki67) (Tau-b = - 0.406; p = 0.006). CXCR4 immunostaining was evaluated in 37 TNBC patients (22 with paired tumor-normal adjacent tissue). CXCR4 was detected more intensely in cell cytoplasm than in membrane, and was more expressed in tumor than in normal adjacent tissues, although not statistically significant. CXCR4 expression on the membrane of tumor cells was correlated positively with histopathological grade (Tau-b = 0.271; p = 0.036) and negatively with lymph node metastasis (Tau-b = - 0.478; p = 0.036). The present study indicates that CXCL12 and CXCR4 polymorphisms and CXCR4 immunostaining might have susceptibility and prognostic roles in TNBC pathogenesis.

HER2 Ile655Val polymorphism is negatively associated with breast cancer susceptibility.

BACKGROUND: The HER2 (human epidermal growth factor receptor-2) Ile655Val (rs1136201) genetic polymorphism can alter the receptor structure and its auto-activation, which can modify the signal transduction and, consequently, the cell cycle regulation. For this reason, this polymorphism has been extensively investigated as a candidate marker for breast cancer (BC). In this context, the aim of this study was to evaluate the possible influence of HER2 Ile655Val in BC susceptibility and prognostic factors in a Brazilian population. METHODS: Polymorphism genotype was assessed through RFLP-PCR in 107 BC patients with clinicopathological data available and in 150 women with no evidence of neoplasia and with no familial history of BC as control group. Association between this polymorphism and BC susceptibility and clinical parameters was evaluated through odds ratio (OR) and chi-squared or Fisher's exact test, respectively. RESULTS: A significant negative association between valine allele and BC susceptibility in dominant model was found (OR 0.5; 95% CI 0.27-0.93, P = .036). No significant association was found in relation to BC clinicopathological features (tumor size, lymph nodes commitment, histological grade, HER2 overexpression, hormonal receptors, p53, and Ki-67). CONCLUSION: Although this polymorphism did not demonstrate potential as a prognostic marker, it may be a suitable susceptibility marker for BC.

Transforming growth factor beta 1 (TGFß1) polymorphisms and haplotype structures have dual roles in breast cancer pathogenesis.

PURPOSE: Despite the documented dual role of TGFß1 in breast cancer (BC) pathogenesis, the subtype-specific influences of its polymorphisms remain undocumented. The present study investigated the effects of the TGFB1 promoter region (rs1800468 or G-800A and rs1800469 or C-509T) and signal peptide (rs1800470 or C29T and rs1800471 or G74C) single nucleotide polymorphisms (SNPs) and their haplotype structures on the susceptibility and clinicopathological presentation of BC subtypes. METHODS: TGFB1 genotypes were assessed by PCR-RFLP and haplotype structures were inferred for 323 BC patients and 405 neoplasia-free women, and case-control analyses were performed by logistic regression adjusted by age. Clinicopathological parameters (age at diagnosis, tumor size, histopathological grade, lymph node metastasis, proliferation index and disease stage) were tested for correlation with TGFB1 variants. All statistical analyses were two-tailed with an alpha level of 0.05. RESULTS: Variants related to increased TGFß1 production (C-509T SNP and GTCG haplotype) were associated with increased susceptibility to HER2+ tumors and correlated with worse prognostic parameters in HER2+ and triple-negative (TN) BCs, but correlated negatively to Ki67 in ER/PR+HER2- tumors. Conversely, low TGFß1 production variants (C29T SNP and GCTG haplotype) were protective against HER2+ tumors and correlated negatively with prognostic parameters in HER2+ and TN BCs, while indicating higher proliferation rates in ER/PR+HER2- tumors. Furthermore, the GCCG haplotype was associated with decreased susceptibility to ER/PR+HER2- tumors, but correlated positively with Ki67 in this subgroup. CONCLUSION: The present study indicates that TGFB1 variants have subtype-specific roles in BC and may switch from tumor suppressor to promoter during tumor development, consistent with TGFß1 dual role in BC pathogenesis.

FOXP3 Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes.

FOXP3 genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1.93; 95% CI = 1.01-3.66; p = 0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (τ = 0.47; p = 0.019) and advanced TNM staging in TN (τ = 0.23; p = 0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (τ = -0.47; p = 0.018) and lower histological grade (τ = 0.39; p = 0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (τ = -0.15; p = 0.009) and higher Ki-67 (τ = 0.43; p = 0.036) in HER2+ and advanced staging in TN (τ = 0.29; p = 0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (τ = -0.54; p = 0.005) and staging (τ = -0.29; p = 0.027) in HER2+ and TN respectively. Results showed that FOXP3 influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes.

Wilms' tumor susceptibility: possible involvement of FOXP3 and CXCL12 genes.

BACKGROUND: Wilms' tumor is an embryonal neoplasm of the kidney that accounts for approximately 6 % of all childhood tumors. The chemokine CXCL12 (C-X-C chemokine ligand 12) and its ligand CXCR4 (C-X-C chemokine receptor type 4) are involved in the development of several organs, including the kidney, and are also associated with tumor growth and metastasis. FOXP3 (forkhead transcription factor 3) was initially described as a marker for regulatory T cells; however, its expression in several types of tumor cells has already been described and may have prognostic significance. The aim of the present study was to analyze rs3761548 and rs2232365 FOXP3 polymorphisms, as well as evaluate rs1801157 CXCL12 polymorphism in Wilms' tumor samples. METHODS: Polymorphisms were evaluated in 32 patients and 78 neoplasia-free controls. Genotypes of rs1801157 were determined using PCR-restriction fragment length polymorphism (PCR-RFLP) method, and genotypes of rs2232365 and rs3761548 were determined using allele-specific PCR (AS-PCR). RESULTS: The case-control study indicated a significant association for allele A carriers of rs1801157 polymorphism in relation to Wilms' tumor susceptibility (OR = 5.261; 95 % CI 2.156 to 12.84; p = 0.0002). The opposite was observed in male carriers of G allele for rs2232365 polymorphism (OR 0.1164; 95 % CI 0.0227 to 0.5954; p = 0.0091) or when male and female subjects were analyzed (OR = 0.1304; 95 % CI 0.05013 to 0.3394; p < 0.0001). CONCLUSIONS: All in all, these markers may contribute to this neoplasia susceptibility and progression; however, further studies are needed to real clarify their role in Wilms' tumor pathogenesis.

Protein Expression and Codon 72 Polymorphism of TP53 Gene in Triple Negative Breast Cancer

A subgroup of tumor that has received attention is triple-negative breast cancer (TNBC), which presents phenotype of negative estrogen receptor, negative progesterone receptor and has no overexpression of HER2. TP53 acts as a tumor suppressor limiting the proliferation of damaged cells. A polymorphic site (rs1042522) of TP53 encodes either an arginine or a proline amino acid, but its biological significance remains unclear. This study aimed to investigate this variant and its expression in search for a possible involvement in TNBC susceptibility and clinical outcome. Genetic polymorphism was evaluated in 50 patients and 115 controls by PCR based methodology and immunohistochemistry was done with monoclonal antibody. Case-control study showed no positive or negative association (OR= 0.95; CI95%= 0.48-1.89). Comparison of genotypes and clinical outcome showed no significant results. Despite most of patients presented p53 positive staining by immunohistochemistry, there was no significant association in relation to prognostic parameters. Results demonstrated a lack of association between codon 72 polymorphism, susceptibility and prognosis of TNBC. Immunohistochemistry analysis should be done more carefully, since most of the patients had the somatic mutation of p53, which could be an indicator of prognostic value in TNBC.

FOXP3 transcription factor: a candidate marker for susceptibility and prognosis in triple negative breast cancer.

Triple negative breast cancer (TNBC) is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2). FOXP3 (forkhead transcription factor 3) is a marker of regulatory T cells (Tregs), whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548) and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction). Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02-14.06) in relation to TNBC susceptibility. Most of the patients (83%) showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P = 0.026). In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

Toll-like receptor 3: implications for proinflammatory microenvironment in human breast cancer.

Under many circumstances, the host constituents that are found in the tumor microenvironment support a malignancy network and provide the cancer cells with advantages in proliferation, invasiveness and metastasis establishment at remote organs. It is known that Toll like receptors (TLRs) are expressed not only on immune cells but also on cancer cells and it has suggested a deleterious role for TLR3 in inflammatory disease. Hypothesizing that altered IFNγ signaling may be a key mechanism of immune dysfunction common to cancer as well CXCR4 is overexpressed among breast cancer patients, the mRNA expression of TLR3, CXCR4 and IFNγ in breast cancer tumor tissues was investigated. No statistically significant differences in the expression of CXCR4 mRNA, IFNγ and TLR3 between healthy and tumor tissues was observed, however, it was verified a positive correlation between mRNA relative expression of TLR3 and CXCR4 (p < 0.001), and mRNA relative expression of TLR3 was significantly increased in breast cancer tumor tissue when compared to healthy mammary gland tissue among patients expressing high IFNγ (p = 0.001). Since the tumor microenvironment plays important roles in cancer initiation, growth, progression, invasion and metastasis, it is possible to propose that an overexpression of IFNγ mRNA due to the pro-inflammatory microenvironment can lead to an up-regulation of CXCR4 mRNA and consequently to an increased TLR3 mRNA expression even among nodal negative patients. In the future, a comprehensive study of TLR3, CXCR4 and IFNγ axis in primary breast tumors and corresponding healthy tissues will be crucial to further understanding of the cancer network.

TGF-ß polymorphism and its expression correlated with CXCR4 expression in human breast cancer.

The role of chemokines and the growth factors has been extensively analyzed both in cancer risk and tumor progression. The transforming growth factor beta (TGF-ß) and chemokine (C-X-C motif) receptor 4 (CXCR4) genes are implicated in several diseases, including breast cancer. Genomic DNA was obtained from 21 samples of peripheral blood or from normal tissue, previously fixed in formalin and embedded in paraffin for TGF-ß T869C polymorphism analyses. Total cellular RNA was extracted from the same 21 patients, but from fresh tissue (tumor and adjacent healthy from the same breast) for expression analysis by Real Time PCR. No significant differences were observed in genotype distribution according to clinicopathological characteristics. Transforming growth factor beta (TGF-ß) mRNA expression was assessed according to T869C polymorphism and CC patients presented a higher TGF-ß expression but not significant when compared to other genotypes (p = 0.064). A positive correlation was observed in relative mRNA expressions of CXCR4 and TGF-ß (p = 0.020). It is known that overexpression of TGF-ß by both tumor and stromal tissue can facilitate the development of metastases, mainly by TGF-ß stimulated angiogenesis and increased tumor cell motility. Our findings suggested a role of these genes as progression markers for breast carcinoma.

Oral carcinoma epidemiology in Paraná State, Southern Brazil.

Oral carcinoma is the sixth most frequent type of cancer in the world and the seventh most common in Brazil (the country with the highest incidence in Latin America). Mean five-year survival remains one of the lowest among the main cancers, thus justifying studies that contribute to the development of preventive strategies. The aim of this study was to compare the epidemiological, clinical, and histological characteristics of 91 patients with oral carcinoma. Mean age was 58.62 +/- 10.46 years, and male-to-female ratio was 6.6:1.0 (79 men and 12 women). European descendants predominated with 79 patients (86.8%). Eighty-five individuals (93.4%) smoked and 70 (76.9%) consumed alcohol regularly. Anatomical distribution of tumors was: 27 (29.7%) tongue; 18 (19.8%) floor of mouth; 11 (12.1%) oropharynx; and 11 (12.1%) oral mucosa. Fifty-seven patients (62.6%) presented lymph node involvement and three (3.3%) had distant metastases. Surgery and radiotherapy were used in 43.2% of patients. With the exception of the male/female ratio (which was higher), our data are consistent with previous studies on oral carcinoma patients.

Oral carcinoma epidemiology in Paraná State, Southern Brazil / Epidemiologia do câncer bucal em pacientes do Estado do Paraná, Sul do Brasil

Oral carcinoma is the sixth most frequent type of cancer in the world and the seventh most common in Brazil (the country with the highest incidence in Latin America). Mean five-year survival remains one of the lowest among the main cancers, thus justifying studies that contribute to the development of preventive strategies. The aim of this study was to compare the epidemiological, clinical, and histological characteristics of 91 patients with oral carcinoma. Mean age was 58.62 ± 10.46 years, and male-to-female ratio was 6.6:1.0 (79 men and 12 women). European descendants predominated with 79 patients (86.8 percent). Eighty-five individuals (93.4 percent) smoked and 70 (76.9 percent) consumed alcohol regularly. Anatomical distribution of tumors was: 27 (29.7 percent) tongue; 18 (19.8 percent) floor of mouth; 11 (12.1 percent) oropharynx; and 11 (12.1 percent) oral mucosa. Fifty-seven patients (62.6 percent) presented lymph node involvement and three (3.3 percent) had distant metastases. Surgery and radiotherapy were used in 43.2 percent of patients. With the exception of the male/female ratio (which was higher), our data are consistent with previous studies on oral carcinoma patients.

O carcinoma bucal é o sexto tipo mais comum de câncer no mundo e o sétimo no Brasil, onde ocorre a maior incidência da América Latina. A sobrevida média de aproximadamente cinco anos permanece como uma das menores entre os principais cânceres, justificando estudos que auxiliem no delineamento de estratégias de prevenção. Este estudo objetivou avaliar em uma amostra de 91 pacientes portadores de carcinomas bucais características epidemiológicas; fatores de risco, clínicos e histopatológicos. A média de idade foi de 58,62 ± 10,46 anos e a razão sexual de 6,6:1,0 (79 homens e 12 mulheres). A etnia euro-descendente foi predominante com 79 (86,8 por cento) pacientes. Oitenta e cinco (93,4 por cento) indivíduos eram tabagistas e 70 (76,9 por cento) etilistas. As localizações anatômicas prevalentes foram: 27 tumores (29,7 por cento) de língua; 18 (19,8 por cento) de assoalho; 11(12,1 por cento) de orofaringe e 11 (12,1 por cento) de mucosa. Cinqüenta e sete (62,6 por cento) pacientes apresentaram os linfonodos comprometidos e três apresentaram (3,3 por cento) metástases à distância. A maioria dos pacientes (43,2 por cento) recebeu tratamento cirúrgico e radioterápico. Com exceção da proporção sexual, nossos dados concordam com os freqüentemente descritos para portadores de carcinomas bucais.

Lack of association among polymorphic xenobiotic-metabolizing enzyme genotypes and the occurrence and progression of oral carcinoma in a Brazilian population.

BACKGROUND: A case control association study was carried out to investigate polymorphisms in genes CYP1A1 (3801T > C), GSTM1, and GSTT1 (null genotypes) and oral squamous cell carcinoma (OSCC), including a correlation with some histopathological findings (tumor size, lymph node invasion and degree of tumor differentiation). PATIENTS AND METHODS: The patients (n = 91) and the controls (n = 81) were matched by age, sex, ethnicity and smoking habits. The molecular analysis was carried out using Polymerase Chain Reaction-Restrict Length Polymorphisms PCR-RFLP (CYP1A1) and Multiplex-PCR (GSTM1/GSTT1). RESULTS: No association was found for any of the studied genes: CYP1A1 (odds ratio (OR) = 1.24; 95% Confidence Interval (CI) = 0.67-2.31), GSTM1 (OR = 0.61; CI 95% = 0.33-1.11), and GSTT1 (OR = 1.24; CI 95% = 0.65-2.38). The analysis of combining genotypes also showed lack of association. Comparison with the histopathological findings did not, in general, detect any statistically significant differences. CONCLUSION: CYP1A1, GSTM1 and GSTT1 polymorphisms do not appear to influence the genetic susceptibility to OSCC or the progression to more advanced stages.

Alterações renais em diabetes mellitus do tipo 2 descrição da histologia em estudo de necrópsia / Renal disease in type 2 diabetes mellitus a renal histological description in autopsies

Introdução: As alterações histológicas renais encontráveis no paciente com Diabetes Mellitus do tipo 2 (DM2) ainda não estão bem estabelecidas, comoo foram aquelas do diabetes tipo l. Acreditamos que esse fato se deve, em parte, à indicação de biópsia renal em DM2 que se restringe aos casos commanifestações clínicas atípicas, como proteinúria nefrótica, função renal comprometida sem retinopatia ou rápida progressão para insuficiência renal.Objetivos: Descrever as alterações da histologia renal presentes em pacientes diabéticos tipo 2 submetidos à necrópsia após óbito por qualquer causa.Métodos: Análise histológica renal pela microscopia comum de 61 rins de humanos diabéticos necropsiados num período de dez anos (janeiro de 1994 ajaneiro de 2004), no Hospital Universitário em Londrina-PR. Resultados: Dos 61 casos analisados, a glomeruloesclerose diabética clássica, comproliferação nodular, se fez presente em tão somente 49,2%, encontrando-se doença glomerular superimposta à glomeruloesclerose diabética em 6,6%,alterações crônicas com predomínio vascular em 13,1% e outra doença glomerular isolada em 31,1%. Discussão: À semelhança de nossos resultados,em três outros estudos também nos rins obtidos por necrópsias em DM2 houve predomínio da nefroesclerose diabética, por vezes associada a outraspatologias renais. Em nosso material de estudo, 44,2% dos casos apresentavam lesão não diabética composta por outra glomerulopatia em 31,1% enefroesclerose hipertensiva em 13,1%. Conclusões: A análise histológica de rins de pacientes com DM2, obtida por necrópsia, encontra-se emconsonância com os dados da literatura mundial. A biópsia renal em diabéticos com nefropatia certamente permitirá reconhecer, nesse contexto, patologiaseventualmente curáveis.

Background: The structural lesions associated with the signs and symptoms of renal disease in type 2 diabetes mellitus are not as well defined as thoseof type 1; the literature refers to findings other than the typical glomerulosclerosis, but the true prevalence of lesions remains to be established. In general,there is a restrictive biopsy policy in the diabetic patient, indicated only in the presence of heavy proteinuria or renal dysfunction with the absence of retinalchanges. Methods: in the department of pathology of our University Hospital we examined by light microscopy the renal tissue of 61 diabetic type 2 patientswho died from different causes to assess the presence and type of renal changes. Results: 30/61 (49.2%) of the patients had classical diabeticglomerulosclerosis; concomitant diabetic lesion and glomerulonephritis was present in 6.6%;isolated glomerulonephritis in 31.1% and predominant vasculardamage in 1.,1%. Discussion: In our study as well as in three other published studies regarding renal autopsy findings of type 2 diabetic patients, almosthalf of the cases presented a non- classic diabetic glomerular lesion and was represented by hypertensive nephrosclerosis or a potentially curableglomerulonephritis. Conclusions: Our findings with respect to the autopsied diabetic type 2 renal histology are in accordance with the medical literature.Prospectively unrestricted kidney biopsy of type 2 diabetic patients should be stimulated to establish the causes of the renal dysfunction and find treatablelesions, thus enabling us to prevent deterioration is some cases.

Relato de caso: glomerulonefrite rapidamente progressiva simulando vasculite sistêmica como forma de apresentação de doença de Fabry / Rapidly progressive glomerulonephritis simulatins systemic vasculitis as presentation form of Fabry's disease

Relata-se um caso de um paciente jovem, do sexo masculino, diagnosticado inicialmente como portador de glomerulonefrite rapidamente progressiva secundária à vasculite sistêmica, no qual o diagnóstico de doença de Fabry foi suspeitado devido à presença de angioceratomas cutâneos e confirmado pela determinação de níveis séricos extremamente reduzidos de alfa-galactosidase A. Embora esta seja uma apresentação renal incomum da doença de Fabry, os autores sugerem que a doença de Fabry seja incluída no diagnóstico diferencial de glomerulonefrites rapidamente progressivas.

Melanoma cutâneo primário em Londrina / Primary cutaneous melanoma in Londrina

A incidência e mortalidade por melanoma vêm aumentando em todo o mundo. São poucos os estudos epidemiológicos nacionais sobre o assunto. Os objetivos foram, detectar a freqüência, analisar e classificar os melanomas cutâneos primários diagnosticados em Londrina no período de 1990 a 1999, segundo as principais características clínicas e histológicas, comparando os dados obtidos com os da literatura nacional e internacional. Exames com diagnóstico de melanoma cutâneo primário, procedentes de três laboratórios de anatomia patológica de Londrina, revisados quanto às variáveis sexo, idade, localização do tumor, tipo histológico, nível de invasão(Clark) e espessura tumoral (Breslow). A análise estatística dos resultados utilizou os testes qui-quadrado e t de Student. Foram identificados 303 tumores, com predomínio feminino (54,46 por cento). A idade variou de 18 a 96 anos, com média de 56,48 por cento. Houve diferença significante (p=0,017) da localização em relação ao sexo, com maior número de tumores no tronco nos homens em relação às mulheres, nas quais predominou a localização nos membros inferiores. Do total da amostra, 202 representavam melanomas invasivos integralmente ressecados. Os tipos mais freqüentes foram o melanoma nodular (41,09 por cento) e o melanoma disseminativo superficial (37,13 por cento). A maior proporção dos tumores estudados estavam classificados nos níveis do invasão III e IV (70,30 por cento). A espessura variou de 0,12 a 22,50mm, com média de 3,17mm e mediana de 2,06mm. Setenta e cinco por cento dos tumores avaliados mostraram espessura acima de 0,75mm. O melanoma cutâneo primário em Londrina apresenta padrões de distribuição por sexo, idade e localizações semelhantes aos classicamente reconhecidos em todo o mundo. No entanto, apresenta diferenças em relação à proporção de diagnósticos por tipo histológico, com maior número de melanomas nodulares e níveis de invasão e espessura tumoral mais avançados em relação aos estudos internacionais