Polymorphisms of Lewis and Secretor genes are related to breast cancer and metastasis in axillary lymph nodes.

ABH and Lewis antigen expression has been associated with cancer development and prognosis, tumor differentiation, and metastasis. Considering that invasive ductal breast carcinoma (IDC) presents multiple molecular alterations, the aim of the present study was to determine whether the polymorphism of ABO, Lewis, and Secretor genes, as well as ABO phenotyping, could be associated with tumor differentiation and lymph nodes metastasis. Seventy-six women with IDC and 78 healthy female blood donors were submitted to ABO phenotyping/genotyping and Lewis and Secretor genotyping. Phenotyping was performed by hemagglutination and genotyping by the polymerase chain reaction with sequence-specific primers. ABO, Lewis, and Secretor genes were classified by individual single nucleotide polymorphism at sites 59, 1067, 202, and 314 of the Lewis gene, 428 of the Secretor gene, and 261 (O1 allele), 526 (O2 and B allele), and 703 (B allele). No association was found between breast cancer and ABO antigen expression (P = 0.9323) or genotype (P = 0.9356). Lewis-negative genotype was associated with IDC (P = 0.0126) but not with anatomoclinical parameters. Nonsecretor genotype was associated with axillary lymph node metastasis (P = 0.0149). In conclusion, Lewis and Secretor genotyping could be useful to predict respectively breast cancer susceptibility and axillary lymph nodes metastasis.

Computer-assisted analysis of cell proliferation markers in oral lesions.

Abnormalities in any component of the cell cycle regulatory machine may result in oral cancer, and markers of cell proliferation have been used to determine the prognosis of tumor progression. The aim of this study was to determine whether silver-stained nucleolar organizer region (AgNOR) and Ki-67 measurements could improve the assessment of growth rates in oral lesions. Eighty-three oral biopsies were studied, 20 of which were classified as fibrous inflammatory hyperplasia (FIH), 40 as leukoplakia (LKP) and 23 as oral squamous cell carcinoma (OSCC). Within the LKP group, 22 out of 29 biopsies were diagnosed as non-dysplastic leukoplakia (LK) and 18 as dysplastic leukoplakia (DLK), presenting discrete, moderate and severe dysplasia. Ki-67 immunolabeling of the lesions increased steadily in the following order: FIH, DLK, LK and OSCC, indicating that Ki-67 is a good marker for predicting the proliferative fraction among benign, premalignant and malignant oral lesions. The median values of AgNOR parameters indicate that the morphometric index gives better results regarding the proliferative rate than the numerical one. A series of linear regressions between AgNOR parameters and Ki-67 showed positive associations. We conclude that a combination of Ki-67 and morphometric AgNOR analyses could be used as an aid in the determination of the proliferative status of oral epithelial cells in oral cancer.

p16(INK4A) immunohistochemical overexpression in premalignant and malignant oral lesions infected with human papillomavirus.

Human papillomavirus (HPV) is believed to promote the oncogenic process, and the correlation between viral oncoproteins and dysfunction of p16(INK4A) tumor suppressor protein in oral lesions is controversial. To test the hypothesis that anogenital HPV types participate in disruption of the regulation of p16(INK4A) suppressor protein in oral lesions, we analyzed 46 oral biopsy specimens for the presence of HPV 6/11 and 16/18 by in situ hybridization (ISH) and for p16(INK4A) expression by immunohistochemistry (IHC). Eighteen (39%) of the 46 oral lesions were HPV-positive and 28 (61%) were HPV-negative. HPV 6/11 DNA was found in 5 (11%) and HPV 16/18 in 13 (28%) of 46 biopsies. Nine of the 18 HPV-positive oral lesions (50%), assessed by catalyzed signal amplification coupled to ISH (CSA-ISH), gave high-intensity p16(INK4A) immunostaining. Focal and diffuse patterns were observed in 11/13 (77%) lesions with HPV 16/18, focal immunopositivity in 3/5 (80%) with HPV 6/11, and negative or sporadic p16-labeling in 18/28 (64%) without the presence of HPV DNA. These results showed a strong association between overexpression of p16 protein and malignant oral lesions, mainly those infected by HPV 16/18. We can conclude that high-risk HPV types are associated with p16 overexpression, and p16 may serve as a biomarker in oral cancer related to high-risk HPV infection.

Computer-assisted analysis of p53 and PCNA expression in oral lesions infected with human papillomavirus.

OBJECTIVE: To carry out a retrospective study to determine whether human papillomavirus (HPV) infection and immunohistochemical expression of p53 and proliferating cell nuclear antigen (PCNA) are related to the risk of oral cancer. STUDY DESIGN: Fifty-seven oral biopsies, consisting of 30 oral squamous papillomas (OSPs) and 27 oral squamous cell carcinomas (OSCCs) were tested for the presence of HPV 6/11 and 16/18 by in situ hybridization using catalyzed signal amplification and in situ hybridization. p53 And PCNA expression was analyzed by immunohistochemistry and evaluated quantitatively by image analysis. RESULTS: Nineteen of the 57 oral lesions (33.3%) were positive for HPV. HPV 6/11 was found in 6 of 30 (20%) OSPs and 1 of 27 (3.7%) OSCCs. HPV 16/18 was found in 10 of 27 (37%) OSCCs and 2 of 30 (6.7%) OSPs. Sixteen of the 19 HPV-positive cases (84.2%) were p53 negative; 5 (9%) were HPV 6/11 and 11 (19%) HPV 16/18, with an inverse correlation between the presence of HPV DNA and p53 expression (P = .017, P < .05). PCNA expression appeared in 18 (94.7%) of HPV positive cases, showing that HPV 16/18 was associated with intensity of PCNA expression and with OSCCs (P = .037, P < .05). CONCLUSION: Quantitative evaluation of p53 by image analysis showed an inverse correlation between p53 expression and HPV presence, suggesting protein degradation. Image analysis also demonstrated that PCNA expression was more intense in HPV DNA 16/18 OSCCs. These findings suggest involvement of high-risk HPV types in oral carcinogenesis.

Papilomavírus humano (HPV) em lesões benignas e malignas de mucosa oral pelos métodos de imuno-histoquímica e hibridização in situ / Human papillomavirus (HPV)in benign and malignant oral lesions by immunohistochemistry and in situ hybridization methods

Quinze biópsias orais com diagnóstico histopatológico de papiloma (n=7), e carcinoma espinocelular invasivo (n=8) foram investigadas para a presença do papilomavírus humano (HPV) por imuno-histoquímica (IHQ) e hibridização in situ (HIS). As proteínas do capsídeo viral foram avaliadas por imuno-histoquímica com anticorpo policlonal e o DNA do vírus analisado por hibridização in situ com sondas biotiniladas de amplo espectro, 6/11 e 16/18. O HPV foi detectado por IHQ em 13 por cento (n=2) e, por HIS, em 60 por cento (n=9) das lesões orais. As duas biópsias positivas na IHQ também foram positivas para a presença do DNA de HPV 6/11. Além disso, o HPV 16/18 foi encontrado em 20 por cento dos carcinomas orais e em 7 por cento dos papilomas, enquanto o HPV 6/11 foi detectado em 7 por cento dos carcinomas e 26 por cento dos papilomas. Pode-se concluir deste estudo que a reação imuno-histoquímica é pouco sensível para o diagnóstico de HPV e que a presença do HPV 16/18 em lesões benignas e malignas sugere a participação deste vírus na carcinogênese oral.

Bioaerossóis em ambientes do prédio tradicional da Faculdade de Ciências Farmacêuticas - UNESP / Microbial bioaerosols in environments of the Traditional Building at the School of Pharmaceutical Sciences

Este trabalho objetivou conhecer a concentraçäo microbiana e a influência de alguns fatores ambientais na dispersäo de bioaerossóis em cômodos específicos, de uso restrito e público, do Prédio Tradicional da Faculdade de Ciências Farmacêuticas, onde situa o Departamento de Análises Clínicas, Farmácia Escola e Unidade Auxiliar. As amostragens foram realizadas utilizando-se o MAS-100, durante 2 períodos do ano, em 15 cômodos, sendo 5 laboratórios didáticos, 5 laboratórios de rotina e 5 salas de atendimento ao público. Os ambientes foram analisados em relaçäo ao tipo de climatizaçäo (natural ou artificial) e ao número de ocupantes. O tipo de climatizaçäo demonstrou näo influenciar no número de unidades formadoras de colônia por metro cúbico de ar dos diferentes ambientes. Diferenças significativas foram observadas em ambientes onde circulavam menos de 9 e 9 ou mais pessoas, independentemente do tipo de atividade desenvolvida. O fato de os próprios ocupantes serem as fontes mais prováveis de bioaerossóis em ambientes interiores estimula a instalaçäo de equipamentos eficientes que promovam a filtraçäo e renovaçäo do ar, diluindo partículas originadas dentro deles, principalmente naqueles onde há maior fluxo de indivíduos.