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Alfredo Ribeiro-Silva

Publications and source records attributed to Alfredo Ribeiro-Silva.

At least 19 recordsLinked to original sources

Tumor-infiltrating CD4+ T lymphocytes in early breast cancer reflect lymph node involvement.

BACKGROUND: The role of immune system in the pathogenesis and progression of breast cancer is a subject of controversy, and this stimulated us to investigate the association of the immunophenotype of tumor-infiltrating lymphocytes in early breast cancer with the spread of tumor cells to axillary lymph nodes. METHODS: Tumor samples from 23 patients with early breast cancer from the Department of Gynecology and Obstetrics of Ribeirão Preto Medical School (USP) were obtained at the time of biopsy and submitted to an enzyme-digestion procedure for the extraction of tumor-infiltrating lymphocytes. The lymphocytes extracted were analyzed by dual-color flow cytometry with monoclonal antibodies in these combinations: CD3 FITC/CD19 PE, CD3 FITC/CD4 PE, CD3 FITC/CD8 PE, and CD16/56 PerCP, which are specific for immunophenotyping of T and B lymphocytes, helper and cytotoxic T lymphocytes, and natural killer (NK) cells. The mean percentage of these cells was used for comparing groups of patients with or without lymph node metastasis. RESULTS: The mean value for T-lymphocyte infiltration was 24.72 +/- 17.37%; for B-lymphocyte infiltration, 4.22 +/- 6.27%; for NK-cell infiltration, 4.41 +/- 5.22%, and for CD4(+) and CD8(+) T-lymphocyte infiltration, 12.43 +/- 10.12% and 11.30 +/- 15.09%, respectively. Only mean values of T- and CD4(+) T-lymphocyte infiltration were higher in the group of patients with lymph node metastasis, while no differences were noted in the other lymphocyte subpopulations. CONCLUSION: The association of tumor-infiltrating CD4(+) T lymphocytes with lymph node metastasis suggests a role for these cells in the spread of neoplasia to lymph nodes in patients with early breast cancer.

Adult↗

Expression of p63 and p16 in primary and recurrent pterygia.

BACKGROUND: p63 and p16 have been described as stem-cell markers of squamous epithelium. In an attempt to obtain new insights into the pathogenesis of pterygium, this study aims to evaluate the relationship between p63 and p16 expression in primary and recurrent pterygia. METHODS: Samples of primary (n=56) and recurrent (n=14) pterygia and normal bulbar conjunctival tissue (n=11) were submitted to immunohistochemical study to evaluate the expression of p63 and p16 in these tissues. RESULTS: Most of the cells stained for p63 were located in the basal layer of the normal conjunctiva, in the lower two-thirds of the epithelium of primary pterygia, and throughout all epithelial layers of recurrent pterygia. In normal conjunctivae, p16 expression was rarely expressed. Primary and recurrent pterygium groups exhibited increased p16 expression, with cytoplasmic staining in the primary group, and cytoplasmic or nuclear staining in the recurrent group. CONCLUSION: The overexpression of p63 and p16 observed in the present study reinforces likelihood of involvement of these genes in the pathogenesis of pterygium, perhaps related to the intense cellular turnover with substitution of superficial epithelial cells by less differentiated forms. This loss of normal cellular differentiation of the epithelial layers could explain the high rates of recurrence overall in the recurrent pterygia.

Cyclin-Dependent Kinase Inhibitor p16↗

Immunohistochemical expression of p16, p53, and p63 in colorectal adenomas and adenocarcinomas.

PURPOSE: The aim of this study was to investigate the immunohistochemical expression of p16, p53, and p63 proteins according to some pathologic parameters related to colorectal adenomas and adenocarcinomas such as grade of dysplasia and histologic type. METHODS: Immunohistochemistry with the antibodies p16, p53, and p63 was performed in tubular, tubular-villous, and villous adenomas (n = 30) and in well, moderately, and poorly differentiated adenocarcinomas (n = 30). The p63-positive cases were submitted to double immunolabeling with the cytokeratin 5 (CK5). RESULTS: The p16 and p53 labelings were observed in some adenomas and adenocarcinomas but without any association with p63 expression, histologic type, or grade of differentiation of the neoplasm. P63 expression was found mainly in the villous adenomas and in the poorly differentiated adenocarcinomas. The poorly differentiated adenocarcinomas also exhibited coexpression of CK5 and p63. CONCLUSIONS: Despite both p16 and p53 having been detected in colorectal neoplasms, they were not related to the different histologic variables nor to the expression of p63. However, p63 expression was closely associated with villous adenomas and poorly differentiated adenocarcinomas. Thus, p63 may represent a marker of poor differentiation in colorectal neoplasms. The coexpression of p63 and CK5 observed in this study could be related to divergent differentiation during the development of colorectal cancer, although further studies are warranted to refine the understanding of this process.

Adenocarcinoma↗

Apoptosis induced by neoadjuvant chemotherapy in breast cancer.

AIM: To evaluate the relationship between apoptosis induced by chemotherapy and clinical response in breast cancer. METHODS: Apoptosis index (AI), mutant p53 and Bcl-2 protein expression were evaluated in 44 breast tumour samples from patients submitted to neoadjuvant chemotherapy. Objective response (OR) to primary chemotherapy was observed in 37 patients (84%) and no response (NR) in seven. AI was measured by the rate of apoptotic cells identified using morphological criteria. p53 and Bcl-2 protein expression were evaluated using an immunoperoxidase staining technique. RESULTS: The median AI change observed between pre-chemotherapy AI and post-chemotherapy AI was 0.84 in the OR group and 0.01 in the NR group, (rho = 0.4; p = 0.006). There was no change in Bcl-2 protein expression following chemotherapy. In the OR group, p53 protein expression was positive in 41.6% of patients before and in 22.2% after chemotherapy (difference = 16.6%; p = 0.03). No change was detected in the NR group. CONCLUSION: A positive correlation was found between the increase in AI and clinical response to neoadjuvant chemotherapy in locally advanced breast cancer.

Adult↗

Vascular endothelial growth factor expression in the basal subtype of breast carcinoma.

The recognition of subtypes of breast carcinomas based on their molecular features has brought new perspectives in breast cancer research. Some key regulators of angiogenesis and tumor infiltration were evaluated in breast carcinomas of basal phenotype (cytokeratin [CK]5+). Immunohistochemical analysis with 14 primary antibodies was performed in 100 formalin-fixed, paraffin-embedded samples of invasive ductal carcinomas. CK5 correlated with indicators of poor outcome, including precocious age, high histologic grade, lymph node positivity, advanced pathologic stage, negativity for hormonal receptors, and a high proliferative rate (Ki-67 labeling index). CK5 also correlated with vascular endothelial growth factor (VEGF) expression but not with the microvessel density. Considering that VEGF-overexpressing neoplastic mammary cells display increased proliferative activity in vitro regardless of the angiogenic effect of VEGF, the differential expression of VEGF might contribute to the more aggressive behavior of these neoplasms. CK5 correlated with tissue inhibitor of metalloproteinase (TIMP)-1, but not matrix metalloproteinase (MMP)-1, MMP-2, extracellular matrix metalloproteinase inducer, TIMP-2 or plasminogen activator inhibitor, indicating that antiproteolytic stimuli might be preponderant in these neoplasms.

Adult↗

Metastases to the breast from extramammary malignancies: a clinicopathologic study of 12 cases.

Along with a brief review of the literature, we report the clinicopathologic features of 12 cases of extramammary malignancies metastatic to the breast. Histological diagnoses of the primary tumor were as follows: non-Hodgkin diffuse large B-cell lymphoma (3 patients), acute mycloid leukemia (3 patients), serous papillary adenocarcinoma, well-differentiated adenocarcinoma, squamous cell carcinoma, undifferentiated neoplasm, mesothelioma, and melanoma. The most common mammographic finding was a well-circumscribed mass with increased density but without speculation, calcifications or other signs that characterize the majority of primary carcinomas. Ultrasound revealed well-circumscribed masses without retrotumor acoustic shadowing. The interval between diagnosis of primary cancer and the appearance of breast metastasis ranged from 0 to 108 months (mean: 17, median: 1). Survival after the detection of the breast metastases ranged from 0.2 to 144 months (mean: 23, median: 9.5). In conclusion, metastasis can mimic either benign disease or primary malignancy and is often an unexpected diagnosis in a patient presenting with a breast mass. Thus, an accurate diagnosis is important to avoid unnecessary mutilating surgery. These masses generally indicate disseminated metastatic disease, with a very poor survival rate.

Adolescent↗

The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen.

Orlistat is an anti-obesity agent that increases the fecal fat excretion, which promotes colon carcinogenesis. Therefore, the present study was designed to verify the effects of Orlistat on the formation of rat colonic aberrant crypt foci (ACF) and cell proliferation evaluated by the PCNA method. Male Wistar rats received either a standard diet or a high fat diet (HFD), supplemented or not with Orlistat (200mg/kg chow) and two doses of the carcinogen dimethyl-hydrazine (25mg/Kg). After 30 days, Orlistat was associated to a significant increase in the number of colonic ACFs and cell proliferation in DMH-treated animals, independently of the HFD.

1,2-Dimethylhydrazine↗

[Endocervical schistosomiasis].

We report the case of an asymptomatic 38-year-old woman that sought medical assistance due to infertility. The gynecological examination showed an endocervical polyp measuring 1.0 x 0.8 x 0.5 cm. A biopsy was performed. Under microscopy, several granulomas containing eggs of Schistosoma mansoni were seen.

Adult↗

Lymphomatoid papulosis in a patient with Waldenström's macroglobulinemia.

Lymphomatoid papulosis (LyP) is a rare skin disease with a benign course but a malignant histologic appearance based on atypical lymphocytes. Waldenström's macroglobulinemia (WM) is a diffuse infiltration of the bone marrow by cells that synthesize IgM immunoglobulins. A 46-year-old female presented with a two year history of weakness, fatigue, anemia, and recurring multiple erythematous papules and nodules in the skin. The skin biopsy showed pleomorphic lymphoid cells with atypical mitoses permeated by a diffuse dermal infiltrate of normal appearing lymphocytes. The neoplastic cells were positive for CD30, CD3, and CD5 but negative for CD20 and EMA. The bone marrow was hypercellular due to a diffuse infiltration by lymphocytes, plasma cells, and plasmacytoid lymphocytes. LyP is a lymphoproliferative disorder of CD30-positive T cells that may be associated with other lymphoid malignancies, particularly Hodgkin's disease, mycosis fungoides, and anaplastic T cell lymphomas. To our knowledge, this is the first report of a LyP appearing in a patient with WM.

Bone Marrow Cells↗

The autopsy in a tertiary teaching hospital in Brazil.

A high autopsy rate allows accurate epidemiological studies and quality control of medical care. This study aims to analyze all autopsies performed in a university teaching hospital in Brazil during 52 consecutive wk. The following data were retrieved from individual autopsy records: gender, age, time of death (hr, day, and month), and the main cause of death. There were 1419 autopsies (79% adults and 21% pediatrics, 60% male and 40% female). Those performed during working days summed up to 67.5%, the remaining 32.5% were performed during weekends or holidays. Autopsies were more frequent during the nocturnal than diurnal period (52.6% vs 47.4%, respectively). The causes of death distributed among the ICD-10 categories were: cardiovascular diseases 21.3%, infectious diseases 19.2%, neoplasms 12.8%, perinatal conditions 10.8%, respiratory diseases 6.6%, gastrointestinal diseases 6.0%, congenital anomalies 4.7%, CNS diseases 3.8%, genitourinary diseases 1.8%, and others 13.0%. There was coexistence of the diseases typical of both industrialized and developing countries, indicating the epidemiological transition in our country. Our data indicate that staff supervision of undergraduate medical students and residents is adequate. Along with a brief discussion of the historical, cultural, and legal factors that allow a high autopsy rate, this study reinforces the importance of the autopsy in a tertiary teaching hospital.

Adolescent↗

Spiradenocarcinoma of the breast arising in a long-standing spiradenoma.

The embryologic origin of the breast is related to salivary and sweats glands. Thus, breast neoplasms may show differentiation toward these tissues, although this is a rare event in humans. We report the clinicopathologic and immunohistochemical features of a 57-year-old woman presenting with a spiradenoma that originated in breast tissue and became malignant 40 years later. Some histogenetic concepts relevant to this case are discussed, along with a brief review of this neoplasm.

Adenoma, Sweat Gland↗

Clinicopathological and immunohistochemical features of a sebaceous carcinoma arising within a benign dermoid cyst of the ovary.

Pure sebaceous neoplasms arising in dermoid cysts of the ovary are exceedingly rare. A 63-year-old female with abdominal swelling and pain underwent a right salpingo-oophorectomy that showed a unilocular cyst weighing 830 g and measuring 15x12x10 cm, filled with sebaceous material containing a few hair shafts. The cyst wall exhibited plaques protruding into the cavity of the cyst. Microscopy revealed a dermoid cyst with nests and lobules of atypical and infiltrating sebaceous cells surrounded by basaloid cells. The tumor cells stained diffusely for high-molecular-weight cytokeratins and focally for cytokeratin 7, cytokeratin 19, epithelial membrane antigen and carcinoembryonic antigen in the immunohistochemistry study. Low-molecular-weight cytokeratins, cytokeratin 20, vimentin, S100, p63, estrogen receptor, progesterone receptor, p53 and c-erbB-2 were negative in tumoral cells. The proliferative labeling index (Ki67 and proliferating cell nuclear antigen) was low. Basal cell carcinoma with sebaceous differentiation and sebaceoma must be considered in the differential diagnosis. However, the presence of obvious malignant sebaceous differentiation in nearly every tumor nest and lack of peripheral palisading and peri-tumoral myxoid stroma excluded these diagnoses. Some histogenetic concepts relevant to this case are discussed along with a brief review of this neoplasm. To our knowledge, this is the sixth case report of a sebaceous carcinoma arising in a mature cystic teratoma of the ovary.

Adenocarcinoma, Sebaceous↗

Is p63 reliable in detecting microinvasion in ductal carcinoma in situ of the breast?

P63, a p53 homologue, is considered to be a marker of myoepithelial cells in breast tissue. This study was carried out to determine the sensitivity of p63 in detecting myoepithelial cells in DCIS and to compare the results obtained with smooth-muscle actin (1A4) in an attempt to verify the reliability of p63 as a possible marker of microinvasion in breast carcinoma. Fifteen DCIS of the breast were submitted to immunohistochemical analysis with anti-p63 and 1A4 antibodies and to a double immunolabeling study using p63 with 1A4. The double immunolabeling study showed that the same cells positive for p63 were also positive for 1A4. The three cases of DCIS with micro-invasion were negative for p63 and 1A4 in the foci of invasiveness. P63 staining was continuous in five of twelve cases of DCIS without microinvasion, being focal and discontinuous in 6 cases and completely negative in one case. Smooth-muscle actin staining was continuous in nine of twelve cases, including the five cases positive for p63. Smooth-muscle actin was focal and discontinuous in only two cases, which were also discontinuous for p63. The DCIS negative for p63 was also negative for 1A4. In conclusion, our results confirm the data of literature that p63 is a specific marker of myoepithelial cells in breast tissue. However, p63 is not as sensitive as 1A4 in staining myoepithelial cells and lack of p63 expression cannot be used as a reliable marker of invasiveness in ductal carcinoma in situ of the breast.

Actins↗

The relationship between p63 and p53 expression in normal and neoplastic breast tissue.

CONTEXT: p63 is a recently described p53 homologue. Despite structural homology, they have different activities. OBJECTIVES: To obtain new insights into the role of p63 in normal and neoplastic breast tissue and to verify the possible association between p63 and p53 in breast carcinomas. DESIGN: Immunohistochemistry in 85 breast carcinomas using p63, smooth muscle actin (1A4), p53, estrogen receptor, and progesterone receptor. The p63-positive cases were submitted to a double-immunolabeling study using p63 with 1A4, cytokeratin 7, and 34betaE12. Clinical data were retrieved from medical files. RESULTS: p63, like 1A4, stained a single and continuous layer surrounding normal breast ductal and alveolar epithelium. In carcinomas, p53 was expressed in 21.17% of carcinomas, whereas p63 was expressed only in poorly differentiated ductal carcinomas (11.76% of cases). p63-positive cells coexpressed 1A4 and 34betaE12, but not cytokeratin 7. Expression of p63 correlated with pathologic staging, tumor size, histologic grading, nodal metastasis, and estrogen receptor negativity. CONCLUSIONS: p63 is a specific myoepithelial cell marker in normal breast tissue and is expressed in a minority of breast carcinomas, being seen only in grade III ductal carcinomas. In ductal carcinomas, malignant p63-positive cells have an immunophenotype similar to that of myoepithelial cells, suggesting that these cells originate from a primary progenitor cell that underwent divergent differentiation to ductal and myoepithelial cells during clonal expansion. Our study argues against a direct role in mammary tumorigenesis. However, p53 is rarely coexpressed with p63, suggesting that p63 could act indirectly as an oncogene by inhibiting p53. This hypothesis could also explain why p63 correlated with several other indicators of poor prognosis.

Adult↗

Malignant Struma Ovarii: an autopsy report of a clinically unsuspected tumor.

BACKGROUND: Struma Ovarii represents less than 3% of ovarian teratomas. The malignant counterpart is very rare. CASE: A 67-year-old female with ascites and progressive weight loss died of respiratory failure secondary to severe chronic obstructive pulmonary disease. Autopsy revealed ascites, hepatic cirrhosis, emphysema, and bronchiectasis. As an incidental finding was seen a huge tumor (10 x 9.5 x 6 cm) in the left ovary. Multiple nodules were detected in the lungs. The thyroid was normal. Microscopy revealed a follicular variant of papillary carcinoma arising in ectopic thyroid tissue in the ovary with metastasis to lungs and pleura. The thyroid gland tissue was normal. CONCLUSION: To our knowledge, this is the first autopsy report of a clinically unsuspected malignant Struma Ovarii.

Aged↗