FILOMENA MARINO CARVALHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Geographic differences in the distribution of molecular subtypes of breast cancer in Brazil(2014) CARVALHO, Filomena M.; BACCHI, Livia M.; PINCERATO, Katia M.; RIJN, Matt Van de; BACCHI, Carlos E.Background: To compare the distribution of the intrinsic molecular subtypes of breast cancer based on immunohistochemical profile in the five major geographic regions of Brazil, a country of continental dimension, with a wide racial variation of people. Methods: The study was retrospective observational. We classified 5,687 invasive breast cancers by molecular subtype based on immunohistochemical expression of estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 proliferation index. Cases were classified as luminal A (ER and/or PR positive and HER2 negative, Ki-67 < 14%), luminal B (ER and/or PR positive, HER2 negative, and Ki-67 > 14%), triple-positive (ER and/or PR positive and HER2 positive), HER2-enriched (ER and PR negative, and HER2-positive), and triple-negative (TN) (ER negative, PR negative, and HER2-negative). Comparisons of the ages of patients and molecular subtypes between different geographic regions were performed. Results: South and Southeast regions with a higher percentage of European ancestry and higher socioeconomic status presented with the highest proportion of luminal tumors. The North region presented with more aggressive subtypes (HER2-enriched and triple-negative), while the Central-West region predominated triple-positive carcinomas. The Northeast-a region with a high African influence-presented intermediate frequency of the different molecular subtypes. The differences persisted in subgroups of patients under and over 50 years. Conclusions: The geographic regions differ according to the distribution of molecular subtypes of breast cancer. However, other differences, beside those related to African ancestry, such as socioeconomic, climatic, nutritional, and geographic, have to be considered to explain our results. The knowledge of the differences in breast cancer characteristics among the geographic regions may help to organize healthcare programs in large countries like Brazil with diverse economic and race composition among different geographic regions.
- 46,XY DSD due to 17 Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency(2014) MENDONCA, Berenice B.; COSTA, Elaine M.F.; INACIO, Marlene; OLIVEIRA JUNIOR, Ari A.; MARTIN, Regina M.; NISHI, Mirian Y.; MACHADO, Aline Z.; CARVALHO, Filomena Marino; DENES, Francisco Tibor; DOMENICE, Sorahia17beta-hydroxysteroid dehydrogenase 3 deficiency (17beta-HSD3) consists of a defect in the last phase of steroidogenesis, in which androstenedione is converted into testosterone and estrone into estradiol. Patients present female-like or with ambiguous genitalia at birth and most affected males are raised as females. Virilization in subjects with 17beta-HSD3 deficiency occurs at the time of puberty and almost half change to be males. Maintenance of the testes in patients raised male is safe and recommended, except when the testes cannot be positioned inside the scrotum. The phenotype of 46,XY disorders of sex development (DSD) owing to 17beta-HSD3 deficiency is extremely variable and is clinically indistinguishable from other causes of 46,XY DSD such as partial androgen insensitivity syndrome and 5alfa-reductase 2 deficiency. Laboratory diagnosis is based on elevated serum levels of androstenedione and estrone and low levels of testosterone and estradiol, resulting in elevated androstenedione:testosterone and estrone:estradiol ratios, indicating an impairment of the conversion of 17-keto into 17-hydroxysteroids. The disorder is due to homozygous or compound heterozygous mutations in the HSD17B3 gene that encodes the 17beta-HSD3 isoenzyme. Molecular genetic testing confirms the diagnosis and provides the orientation for genetic counseling. Our proposal in this article is to review the reported and our own cases of 17beta-HSD3 deficiency.
- Loss of PTEN expression and AKT activation in HER2-positive breast carcinomas(2014) LIN, Francini de Mattos Lima; BACCHI, Carlos Eduardo; BARACAT, Edmund Chada; CARVALHO, Filomena MarinoPURPOSE: To examine the expression of AKT and PTEN in a series of HER2-positive primary invasive breast tumors using immunohistochemistry, and to associate these expression profiles with classic pathologic features such as tumor grade, hormone receptor expression, lymphatic vascular invasion, and proliferation. METHODS: A total of 104 HER2-positive breast carcinoma specimens were prepared in tissue microarrays blocks for immunohistochemical detection of PTEN and phosphorylated AKT (pAKT). Original histologic sections were reviewed to assess pathological features, including HER2 status and Ki-67 index values. The associations between categorical and numeric variables were identified using Pearson's chi-square test and the Mann-Whitney, respectively. RESULTS: Co-expression of pAKT and PTEN was presented in 59 (56.7%) cases. Reduced levels of PTEN expression were detected in 20 (19.2%) cases, and these 20 tumors had a lower Ki-67 index value. In contrast, tumors positive for pAKT expression [71 (68.3%)] were associated with a higher Ki-67 index value. CONCLUSION: A role for AKT in the proliferation of HER2-positive breast cancers was confirmed. However, immunohistochemical detection of PTEN expression did not correlate with an inhibition of cellular proliferation or control of AKT phosphorylation, suggesting other pathways in these mechanisms of control.
- The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors(2014) ALMEIDA, Bernardo Gomes de Lacerda; BACCHI, Carlos E.; CARVALHO, Jesus P.; FERREIRA, Cristiane R.; CARVALHO, Filomena M.OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.