Cofilin-1 (CFL1), a small protein of 18 kDa, has been studied as a biomarker due to its involvement in tumor cell migration and invasion. Our aim was to evaluate CFL1 as an indicator of malignancy and aggressiveness in sputum samples. CFL1 was analyzed by ELISA immunoassay in the sputum of 73 lung cancer patients, 13 cancer-free patients, and 6 healthy volunteers. Statistical analyses included ANOVA, ROC curves, Spearman correlation, and logistic regression. Sputum CFL1 levels were increased in cancer patients compared to cancer-free patients and volunteers (P<0.05). High expression of sputum CFL1 was correlated to T4 stage (P=0.01) and N stage (P=0.03), tobacco history (P=0.01), and squamous cell carcinoma histologic type (P=0.04). The accuracy of sputum CFL1 in discriminating cancer patients from cancer-free patients and healthy volunteers were 0.78 and 0.69, respectively. CFL1 at a cut-off value of 415.25 pg/mL showed sensitivity/specificity of 0.80/0.70 in differentiating between healthy volunteers and cancer patients. Sputum CFL1 was also able to identify cancer-free patients from patients with lung cancer. The AUC was 0.70 and, at a cut-off point ≥662.63 pg/mL, we obtained 60% sensitivity and 54% specificity. Logistic regression analysis controlled for tobacco history, histologic types, and N stage showed that cancer cell-associated CFL1 was an independent predictor of death. Smoker patients with squamous cell carcinoma, lymph node metastasis and sputum CFL1>1.475 pg/mL showed augmented chance of death, suggesting lung cancer aggressiveness. CFL1 presented diagnostic value in detecting lung cancer and was associated to tumor aggressiveness.

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

OBJETIVO: Analisar a história de rastreamento citológico anterior em mulheres que apresentaram alterações citológicas e confirmação histológica para câncer cervical. MÉTODOS: Estudo transversal com 5.485 mulheres (15-65 anos) que se submeteram a rastreamento para o câncer cervical entre fevereiro de 2002 a março de 2003, em São Paulo e Campinas, SP. Aplicou-se questionário comportamental e foi feita a coleta da citologia oncológica convencional ou em base líquida. Para as participantes com alterações citológicas indicou-se colposcopia e, nos casos anormais, procedeu-se à biópsia cervical. Para investigar a associação entre as variáveis qualitativas e o resultado da citologia, utilizou-se o teste de qui-quadrado de Pearson com nível de significância de 5%. RESULTADOS: Dentre os resultados citológicos, 354 (6,4%) foram anormais, detectando-se 41 lesões intra-epitelial escamosa de alto grau e três carcinomas; em 92,6% revelaram-se normais. De 289 colposcopias realizadas, 145 (50,2%) apresentaram alterações. Dentre as biópsias cervicais foram encontrados 14 casos de neoplasia intra-epitelial cervical grau 3 e quatro carcinomas. Referiram ter realizado exame citológico prévio: 100% das mulheres com citologia compatível com carcinoma, 97,6% das que apresentaram lesões intra-epiteliais de alto grau, 100% daquelas com confirmação histológica de carcinoma cervical, e 92,9% das mulheres com neoplasia intra-epitelial cervical grau 3. A realização de citologia anterior em período inferior a três anos foi referida, respectivamente, por 86,5% e 92,8% dessas participantes com alterações citológicas e histológicas. CONCLUSÕES: Entre as mulheres que apresentaram confirmação histológica de neoplasia intra-epitelial cervical grau 3 ou carcinoma e aquelas que não apresentaram alterações histológicas não houve diferença estatisticamente significante do número de exames citológicos realizados, bem como o tempo do último exame citológico anterior.

OBJECTIVE: To examine previous Pap smear history in women screened for cervical cancer with cytological or histological abnormalities. METHODS: Cross-sectional study in a sample of 5,485 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. A behavioral questionnaire was applied and cervical specimens were obtained for testing by Pap smears or liquid-based cytology. Women who had abnormal cytology were referred for colposcopic examination and, if abnormal, for cervical punch biopsy. To explore factors associated to cervical abnormalities Pearson's chi-was conduted square test at a 5% significance level. RESULTS: Cytological abnormalities were found in 354 women (6.4%) and included 41 high-grade squamous intra-epithelial lesions and 3 carcinomas; 92.7% were normal results. Colposcopy was performed in 289 women, and 145 (50.2%) showed abnormal results. Punch biopsies showed 14 cervical intraepithelial neoplasias grade 3 and 4 carcinomas. Previous Pap smears were reported in all women who had cytology suspected of carcinoma, 97.6% of those with high-grade squamous intra-epithelial lesions, all women with histological diagnosis of carcinoma and 92.9% of those who had cervical intraepithelial neoplasias grade 3 histologically. Previous Pap smear in the last tree years was reported by 86.5% and 92.8% of women with abnormal cytology and biopsy, respectively. CONCLUSIONS: There was no statistically significant difference regarding the number of Pap tests and time since their last test between women with histologically diagnosed carcinoma and cervical intraepithelial neoplasia grade 3 compared with those with normal cytology.

OBJETIVO: Analisar a história de rastreamento citológico anterior em mulheres que apresentaram alterações citológicas e confirmação histológica para câncer cervical. MÉTODOS: Estudo transversal com 5.485 mulheres (15-65 anos) que se submeteram a rastreamento para o câncer cervical entre fevereiro de 2002 a março de 2003, em São Paulo e Campinas, SP. Aplicou-se questionário comportamental e foi feita a coleta da citologia oncológica convencional ou em base líquida. Para as participantes com alterações citológicas indicou-se colposcopia e, nos casos anormais, procedeu-se à biópsia cervical. Para investigar a associação entre as variáveis qualitativas e o resultado da citologia, utilizou-se o teste de qui-quadrado de Pearson com nível de significância de 5%. RESULTADOS: Dentre os resultados citológicos, 354 (6,4%) foram anormais, detectando-se 41 lesões intra-epitelial escamosa de alto grau e três carcinomas; em 92,6% revelaram-se normais. De 289 colposcopias realizadas, 145 (50,2%) apresentaram alterações. Dentre as biópsias cervicais foram encontrados 14 casos de neoplasia intra-epitelial cervical grau 3 e quatro carcinomas. Referiram ter realizado exame citológico prévio: 100% das mulheres com citologia compatível com carcinoma, 97,6% das que apresentaram lesões intra-epiteliais de alto grau, 100% daquelas com confirmação histológica de carcinoma cervical, e 92,9% das mulheres com neoplasia intra-epitelial cervical grau 3. A realização de citologia anterior em período inferior a três anos foi referida, respectivamente, por 86,5% e 92,8% dessas participantes com alterações citológicas e histológicas. CONCLUSÕES: Entre as mulheres que apresentaram confirmação histológica de neoplasia intra-epitelial cervical grau 3 ou carcinoma e aquelas que não apresentaram alterações histológicas não houve diferença estatisticamente significante do número de exames citológicos realizados, bem como o tempo do último exame citológico anterior.

OBJECTIVE: To examine previous Pap smear history in women screened for cervical cancer with cytological or histological abnormalities. METHODS: Cross-sectional study in a sample of 5,485 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. A behavioral questionnaire was applied and cervical specimens were obtained for testing by Pap smears or liquid-based cytology. Women who had abnormal cytology were referred for colposcopic examination and, if abnormal, for cervical punch biopsy. To explore factors associated to cervical abnormalities Pearson's chi-was conduted square test at a 5% significance level. RESULTS: Cytological abnormalities were found in 354 women (6.4%) and included 41 high-grade squamous intra-epithelial lesions and 3 carcinomas; 92.7% were normal results. Colposcopy was performed in 289 women, and 145 (50.2%) showed abnormal results. Punch biopsies showed 14 cervical intraepithelial neoplasias grade 3 and 4 carcinomas. Previous Pap smears were reported in all women who had cytology suspected of carcinoma, 97.6% of those with high-grade squamous intra-epithelial lesions, all women with histological diagnosis of carcinoma and 92.9% of those who had cervical intraepithelial neoplasias grade 3 histologically. Previous Pap smear in the last tree years was reported by 86.5% and 92.8% of women with abnormal cytology and biopsy, respectively. CONCLUSIONS: There was no statistically significant difference regarding the number of Pap tests and time since their last test between women with histologically diagnosed carcinoma and cervical intraepithelial neoplasia grade 3 compared with those with normal cytology.

OBJETIVO: Identificação de freqüência de adenocarcinomas de diferentes sítios primários em derrames cavitários. MATERIAL E MÉTODOS: Foram estudados 2.317 casos: 1.146 de derrame pleural (943 mulheres e 203 homens), 1.168 de ascite (727 mulheres e 441 homens) e três de pericárdio (duas mulheres e um homem) e realizada análise retrospectiva dos prontuários dos pacientes e correlação dos achados clínico-laboratoriais. RESULTADOS: Os sítios primários mais freqüentes em derrames pleurais foram: mama (N = 586 - 51,1%), pulmão (N = 185 - 16,1%: 102 homens e 83 mulheres), ovário (N = 124 - 10,8%); em ascites: estômago (N= 473 - 40,5%: 300 homens e 173 mulheres), ovário (N= 306 - 26.2%) e mama (N = 83 - 7,1%). Desses, 555 casos foram citologicamente positivos para malignidade em derrames pleurais, 541 em ascite e dois em pericárdio. Os sítios primários mais freqüentes em derrames pleurais citologicamente positivos foram: mama (N=288 - 51,9%), pulmão (N=92, 16,6%: 45 homens e 47 mulheres) e ovário (N=54, 9,7%); e, em ascites: ovário (N=205 - 37,9%), estômago (N=202, 37,3%: 119 homens e 83 mulheres) e mama (N=31 - 6,8%). Em 47 derrames pleurais (8,5%) e 37 ascites (6,8%), a origem dos adenocarcinomas persistiu indeterminada. CONCLUSÃO: As freqüências estabelecidas poderão, em associação a dados clínicos,orientar a investigação dos sítios primários de adenocarcinomas metastáticos.

BACKGROUND: Metastatic adenocarcinomas in effusions are frequently observed. Cytologic diagnosis of adenocarcinoma is often precise; unfortunately, the classification of the primary site is not possible in a great number of cases. The scope of this study was to report the frequency of adenocarcinomas in effusions according to the primary site. MATERIAL: We studied 2317 sequential cases: 1146 pleural effusions (943 women and 203 men), 1168 ascitic (727 women and 441 men), and 3 pericardial (2 women and 1 men). METHOD: Retrospective analysis of the records of the patients and correlations of the data of clinical follow up and morphological findings. RESULTS: The primary sites more frequently seen in pleural cavity were: breast (N = 586 - 51.1%), lung (N = 185 - 16.1%: 102 men and 83 women), and ovary (N = 124 - 10.8%); in ascites: stomach (N= 473 - 40.5%: 300 men and 173 women), ovary (N= 306 - 26.2%) and breast (N = 83 - 7.1%). Regarding only the samples of malignant effusions we observed 555 in pleural cavity: breast (N=288 - 51.9%), lung (N=92, 16.6%: 45 men and 47 women) and ovary (N=54, 9.7%). In ascites we reported: ovary (N=205 - 37.9%), stomach (N=202 - 37,3%: 119 men and 83 women) and breast (N=31 - 6.8%). In 47 pleural effusions (8.5%) and 37 ascites (6.8%), the original site of the neoplasia remained undetermined. CONCLUSION: The knowledge of the relative frequencies, associated with clinical information, can be helpful in the selection of further investigation for the metastatic adenocarcinomas.

Os autores avaliaram a concordância diagnóstica cito-histológica de lesões de colo uterino e discutiram as eventuais discrepâncias. OBJETIVO. Averiguar o nível de concordância cito-histológica nos casos da Divisão de Patologia do Instituto Adolfo Lutz (IAL) e aprimorar a estratégia de garantia de qualidade na instituição. MATERIAL E MÉTODO. Estudaram 157 casos consecutivos dos arquivos do IAL em que foram enviadas citologia cérvico-vaginal e biópsia. RESULTADO. Houve concordância absoluta em 119 (75,8%) casos; nos demais, a citologia superestimou 11 lesões (7,0%) e subestimou 27 (17,2%). Observou-se que em 5 casos, inicialmente diagnosticados como inflamatório pela citologia, dois foram, à revisão, considerados como NIC 1; os demais foram ratificados como inflamatórios, apesar de suas respectivas biópsias terem diagnóstico de neoplasia intra-epitelial cervical. CONCLUSÃO. Tais resultados demonstram a importância da correlação cito-histológica para o sistema de garantia de qualidade em diagnóstico citológico e apontam para a colheita como um dos fatores determinantes nas discrepâncias diagnósticas.

The cytohistologic diagnosis concordance of the cervix-uterine lesions was evaluated and the discordances are discussed. PURPOSE. To evalute the level of cytohistological diagnosis agreement in the Pathology Division of the Adolfo Lutz Institute and enhance parameters of quality assurance system developed in this institution. METHODS. The authors retrospectively evaluated 157 pairs of cytologyhistology consecutive cases from the files the Adolfo Lutz Institute (Division of Pathology). RESULTS. Agreement was found in 119 cases (75.8%); in the remaining cases cytologic diagnosis were higher than histology in 11 lesions (7.0%) and lower in 27 (17.2%). We also observed that in 5 cases previously diagnosed as inflammatory, 2 of them were reclassified as CIN 1; after revision, the others remained as inflammatory even though they had a histological diagnosis of CIN. CONCLUSION. These results showed the role of cytohistological correlation to the quality assurance system of cytological diagnosis and also stressed the importance of taking the cervical scrapes with accurate care to avoid diagnostic discrepances.