Biomedical subjects
Fernando Augusto Soares
Publications and source records attributed to Fernando Augusto Soares.
Langerhans cell histiocytosis and its relationship with Epstein-Barr virus.
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Carcinoembryonic antigen (CEA) mimicry by an anti-idiotypic scFv isolated from anti-Id 6.C4 hybridoma.
Since carcinoembryonic antigen (CEA) is expressed during embryonic life, it is not immunogenic in humans. The use of anti-idiotypic (Id) antibodies as a surrogate of antigen in the immunization has been considered a promising strategy for breaking tolerance to some tumor associated antigens. We have described an anti-Id monoclonal antibody (MAb), designated 6.C4, which is able to mimic CEA functionally. The anti-Id MAb 6.C4 was shown to elicit antibodies that recognized CEA in vitro and in vivo. In the present study, we sought to verify whether a single chain (scFv) antibody obtained, the scFv 6.C4, would retain the ability to mimic CEA. Two scFv containing the variable heavy and light chain domains of 6.C4 were constructed with a 15-amino acid linker: one with and another without signal peptide. DNA immunization of mice with both forms of scFv individually elicited antibodies able to recognize CEA.
Computed tomography guided needle biopsy: experience from 1,300 procedures.
CONTEXT AND OBJECTIVE: Computed tomography (CT) guided biopsy is widely accepted as effective and safe for diagnosis in many settings. Accuracy depends on target organ and needle type. Cutting needles present advantages over fine needles. This study presents experience from CT guided biopsies performed at an oncology center. DESIGN AND SETTING: Retrospective study at Hospital do Câncer A. C. Camargo, São Paulo. METHODS: 1,300 consecutive CT guided biopsies performed between July 1994 and February 2000 were analyzed. Nodules or masses were suspected as primary malignancy in 845 cases (65%) or metastatic lesion in 455 (35%). 628 lesions were thoracic, 281 abdominal, 208 retroperitoneal, 134 musculoskeletal and 49 head/neck. All biopsies were performed by one radiologist or under his supervision: 765 (59%) with 22-gauge fine-needle/aspiration technique and 535 (41%) with automated 16 or 18-gauge cutting-needle biopsy. RESULTS: Adequate samples were obtained in 70-92% of fine-needle and 93-100% of cutting-needle biopsies. The specific diagnosis rates were 54-67% for fine-needle and 82-100% for cutting-needle biopsies, according to biopsy site. For any site, sample adequacy and specific diagnosis rate were always better for cutting-needle biopsy. Among 530 lung biopsies, there were 84 pneumothorax (16%) and two hemothorax (0.3%) cases, with thoracic drainage in 24 (4.9%). Among abdominal and retroperitoneal biopsies, there were two cases of major bleeding and one of peritonitis. CONCLUSION: Both types of needle showed satisfactory results, but cutting-needle biopsy should be used when specific diagnosis is desired without greater incidence of complications.
E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of 125 patients.
OBJECTIVES: The treatment of choice for invasive penile carcinoma is amputation and lymphadenectomy. The latter is associated with a high morbidity rate. Analysis of new prognostic factors such as E-cadherin, matrix metalloproteinase (MMP)-2, and MMP-9 may help to select candidates for lymphadenectomy. METHODS: We assessed 125 patients with penile epidermoid carcinoma treated with amputation and bilateral lymphadenectomy. The following factors were analyzed: age, race, disease evolution time, venereal background, clinical and pathologic stage, tumor thickness, differentiation grade, venous and lymphatic embolization, koilocytosis, type of invasion, and E-cadherin, MMP-2, and MMP-9 immunoreactivity. The value of risk factors for lymph node metastases and specific survival was assessed. RESULTS: The mean follow-up was 76.5 months. Clinical N stage (P = 0.001), tumor thickness (P = 0.027), lymphatic permeation (P < 0.001), venous embolization (P = 0.002), corpus cavernosum infiltration (P = 0.002), and low E-cadherin expression (P = 0.032) significantly correlated with the presence of metastases. Independent risk factors for metastases were lymphatic permeation (relative risk [RR] = 5.99; 95% confidence interval [CI] 2.1 to 16.9) and clinical N stage (RR = 5.5; 95% CI = 1.9 to 16.7). Lymph node metastases (RR = 57.9; 95% CI = 7.4 to 453.9), urethral infiltration (RR = 3.5; 95% CI = 1.3 to 9.2), and MMP-9 immunoreactivity (RR = 3.2; 95% CI = 1.2 to 8.3) were considered independent risk factors for disease recurrence. CONCLUSIONS: On univariate analysis, low E-cadherin immunoreactivity was associated with a greater risk of lymph node metastases. High MMP-9 immunoreactivity was an independent risk factor for disease recurrence.
Immunohistochemical determination of estrogen receptor-alpha in vaginal and tumor tissues of healthy and TVT-affected bitches and their relation to serum concentrations of estradiol-17beta and progesterone.
One of the most frequent canine neoplasms is the transmissible venereal tumor (TVT), which affects the male and the female genital tract. The objective of this study was to determine (immunohistochemically) estrogen receptor (ER-alpha) expression in vaginal tissue of healthy bitches and in the vaginal and neoplastic tissues of TVT-affected bitches. Fifty-eight bitches were divided into two groups: tumor group (TVT) and control group (healthy). Canine estrous cycle stages were determined by means of exfoliative vaginal cytology, hormone assays, and macroscopic appearance of ovaries. Samples from vaginal and neoplastic tissues were obtained under general anesthesia, fixed in 10% buffered formaldehyde, embedded in paraffin, and sectioned. Anestrus, proestrus and estrus control females had higher ER-alpha expression than diestrus bitches. Within the tumor group, diestrus bitches had significantly higher ER-alpha expression. Although some samples had expression in the endothelium of blood vessels, no ER-alpha expression was observed in neoplastic tissues. In conclusion, vaginal tissue of tumor and control bitches, under different distinct steroid influences, had different ER-alpha expression, whereas ER-alpha expression was not present in neoplastic tissues.
Front pattern of invasion in squamous cell carcinoma of the penis: new prognostic factor for predicting risk of lymph node metastases.
OBJECTIVES: Treatment of penile carcinoma is based on excision of the primary tumor and regional lymphadenectomies. Lymph node metastasis is the most important prognostic factor, yet it cannot be reliably evaluated by imaging studies or clinical examinations; thus, new prognostic factors such as the pattern of invasion must be investigated. METHODS: The data of 112 patients with penile carcinoma who underwent amputation and lymphadenectomy were analyzed. The clinicopathologic variables were studied, in addition to the front pattern of invasion according to the standards established by the modified criteria of Anneroth and Bryne first used as a part of a prognostic score in squamous cell carcinoma of the oral cavity. The pattern of invasion expresses the tumor-host tissue relationship, demonstrating the infiltrative tumor characteristics. This pattern was defined as infiltrating (invasion in blocks of small solid strands of cell tumors that broadly infiltrated the organ's stroma) and pushing infiltration (tumor cells have invaded large cell blocks with well-defined tumor-host interfaces). RESULTS: The variables that were significantly associated with the presence of lymph node metastases on univariate analysis were clinical N stage (P = 0.011), lymphatic permeation (P <0.001), venous embolization (P = 0.025), and the pattern of invasion (P <0.001). In the multivariate model, the lymphatic permeation, clinical N stage, and invasion type were independent risk factors for lymph node metastases. The follow-up varied from 0.1 to 452.8 months (mean 76.9, median 27.3). CONCLUSIONS: Lymphatic permeation, clinical N stage, and standard infiltrating invasion were independent prognostic variables for the risk of lymph node metastasis.
Synchronous ameloblastoma and orthokeratinized odontogenic cyst of the mandible.
The simultaneous occurrence of ameloblastomas with odontogenic cysts or other non-odontogenic lesions have already been described as combined lesions. However, we are unaware of any report in the English literature of simultaneous occurrence of ameloblastoma and orthokeratinized odontogenic cyst (OOC) occurring as completely distinct lesions. This report shows a case of synchronous ameloblastoma and OOC, located on posterior regions of the mandible, but in distinct sides.
Immunohistochemical expression of p63 in pleomorphic adenomas and carcinomas ex-pleomorphic adenomas of salivary glands.
Alteration of the p63 protein expression has been associated with several human cancers including salivary gland tumors. We sought to assess the p63 expression in pleomorphic adenomas (PA) and carcinoma ex-pleomorphic adenomas (Ca ex-PA), since this protein has been related to myoepithelial phenotype and the biological behavior of cancer. Ten samples of PA and ten of Ca ex-PA were submitted to immunohistochemistry using a monoclonal anti-p63 antibody, clone 4A4. p63 was regularly expressed in myoepithelial cells' nuclei of the normal glandular parenchyma and in PA, but it was completely absent in five out of the ten samples of Ca ex-PA. (P < 0.05 by Fisher's exact test). Apparently, only those cases depicting some myoepithelial differentiation were positive. Our data suggest that loss of myoepithelial differentiation is important in the evolution of Ca ex-PA, and corroborate the hypothesis that p63 antigen may be a useful marker of myoepithelial cells in salivary glands neoplasms.
Gene expression profile associated with response to doxorubicin-based therapy in breast cancer.
PURPOSE: This study was designed to identify genes that could predict response to doxorubicin-based primary chemotherapy in breast cancer patients. EXPERIMENTAL DESIGN: Biopsy samples were obtained before primary treatment with doxorubicin and cyclophosphamide. RNA was extracted and amplified and gene expression was analyzed using cDNA microarrays. RESULTS: Response to chemotherapy was evaluated in 51 patients, and based on Response Evaluation Criteria in Solid Tumors guidelines, 42 patients, who presented at least a partial response (> or =30% reduction in tumor dimension), were classified as responsive. Gene profile of samples, divided into training set (n = 38) and independent validation set (n = 13), were at first analyzed against a cDNA microarray platform containing 692 genes. Unsupervised clustering could not separate responders from nonresponders. A classifier was identified comprising EMILIN1, FAM14B, and PBEF, which however could not correctly classify samples included in the validation set. Our next step was to analyze gene profile in a more comprehensive cDNA microarray platform, containing 4,608 open reading frame expressed sequence tags. Seven samples of the initial training set (all responder patients) could not be analyzed. Unsupervised clustering could correctly group all the resistant samples as well as at least 85% of the sensitive samples. Additionally, a classifier, including PRSS11, MTSS1, and CLPTM1, could correctly distinguish 95.4% of the 44 samples analyzed, with only two misclassifications, one sensitive sample and one resistant tumor. The robustness of this classifier is 2.5 greater than the first one. CONCLUSION: A trio of genes might potentially distinguish doxorubicin-responsive from nonresponsive tumors, but further validation by a larger number of samples is still needed.
Histological classification of 1,025 cases of Hodgkin's lymphoma from the State of São Paulo, Brazil.
CONTEXT AND OBJECTIVE: It is currently asserted that, in industrialized countries, nodular sclerosis is the most frequent type of Hodgkin's lymphoma, in contrast to developing countries, where mixed cellularity and lymphocyte depletion are more frequently seen. The objective was to review histological data from cases of Hodgkin's lymphoma from São Paulo and Campinas cities. DESIGN AND SETTING: Cross-sectional histopathological analysis, in four university hospitals and one cancer care center. METHODS: 1,025 cases diagnosed as Hodgkin's lymphoma between 1990 and 2000 were collected from five institutions; 631 of them (61.5%) had been immunophenotyped using antibodies to CD20, CD3, CD15 and CD30. The relative frequencies of histological types (as informed by the contributing authors, who are hematopathologists in their institutions) were determined according to age and gender. RESULTS: The Hodgkin's lymphoma types were distributed as follows: lymphocyte predominance 4.8%, nodular sclerosis 69.2%, mixed cellularity 21.1% and lymphocyte depletion 4.6%. CONCLUSIONS: The controversy regarding the frequencies of Hodgkin's lymphoma types within the Brazilian setting seems to be due to the small number of cases in previous studies. The present data show a picture close to the situation in the industrialized countries.
Dedifferentiated liposarcoma of the oral cavity with angiosarcomatous dedifferentiation.
We report a unique case of a 42-year-old woman with a dedifferentiated liposarcoma of the soft tissue of the oral cavity with angiosarcomatous dedifferentiation. Liposarcomas compromising the head and neck region are very unusual, and most of the cases in oral cavity show a well-differentiated pattern. Dedifferentiation in liposarcomas occurs in about 10% of the cases and, when it occurs, the dedifferentiated areas usually resemble high-grade fibrosarcoma or pleomorphic sarcoma. Divergent differentiation might also occur. To the best of our knowledge, there are only nine cases of dedifferentiated liposarcoma of the oral cavity, none of which show an angiosarcomatous dedifferentiation.
Pan-cytokeratin immunoexpression in Wilms' tumors: a simple approach for understanding tumor epithelial differentiation.
Wilms' tumor is one of the most common solid tumors in children and is an interesting model for understanding the pathogenesis of embryonal tumors. Cytokeratins are intracellular fibrous proteins present in tissue of epithelial origin. The immunoexpression of the pan-cytokeratin AE1AE3 was studied in paraffin-embedded tissue sections from 24 Wilms' tumors (12 with nephrogenic rests) and also tissue samples from 15 corresponding normal kidneys, to evaluate epithelial differentiation in the genesis of Wilms' tumor. We observed that the intensity of the expression of AE1AE3 in the epithelial component of Wilms' tumors directly correlated with the degree of maturity of the epithelial structures correspondent to the collecting ducts.
Penile metastasis of chondrosarcoma of the jaw.
Metastasis to the penis is an unusual event. Bladder and prostate tumors are the main sources of penile metastasis. Other sites include the rectosigmoid, kidney, and, less frequently, the pancreas, liver, nasopharynx, and lung. Other sources include malignant melanoma and Burkitt's lymphoma. The differential diagnosis includes idiopathic priapism, venereal or infectious disease, tuberculosis, Peyronie's disease, and primary penile tumor. Chondrosarcoma of the jaw is responsible for 10% of all chondrosarcomas that originate with craniofacial bones. Its behavior is usually characterized by local aggression; however, distant metastasis is uncommon. We report a case of chondrosarcoma of the jaw with penile metastasis. This is the first case described in published medical reports.
Correspondence re: Carpentieri DF, Nichols K, Chou PM, Mathews M, Pawel B, Huff D. The expression of WT1 in the differentiation of rhabdomyosarcoma from other pediatric small round blue cell tumors. Mod pathol 2002;15(10):1080-6.
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Myogenesis in Wilms tumors.
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Hepatoblastomas and liver development: a study of cytokeratin immunoexpression in twenty-nine hepatoblastomas.
Hepatoblastomas (HBs) recapitulate liver development. It is possible that HBs result from malignant transformation of hepatic precursor cells, and they may reflect a blockage in normal development. Here we study the expression of cytokeratins (CKs) in order to delineate the immunoprofile and relationship with liver development, as well as vimentin and alphafetoprotein (AFP), of HBs. Immunohistochemistry was performed in a tissue microarray (TMA) containing representative areas of 18 HBs (fetal and/or embryonal and/or mesenchymal); we also reviewed 11 cases not included in the TMA. No cases stained for CKs 1, 5/6, 7, 10, 13, 15, 16, 20, and 34betaE12. CK8 stained 73.07% of fetal, 50% of embryonal, and 18% of mesenchymal areas. CK18 stained 100% of epithelial areas. CK19 staining was intense and diffuse in 100% of embryonal samples, but it was weaker in fetal areas (66.66%). AE1 stained epithelial areas in all cases, and it stained 29.41% of mesenchymal areas. AE3 stained 84.61% of embryonal and 60% of fetal components. AE1/AE3 showed stronger staining in embryonal (100%) than in fetal areas (76.92%). Vimentin staining was strong in embryonal (66.66%) and mesenchymal (84.61%) components but weak in fetal areas (8%). Alphafetoprotein was positive in only 20% of fetal and 70% of embryonal areas. Our results support the hypothesis that immunoexpression of HBs follows the stages of normal liver development. Embryonal areas look less differentiated, expressing vimentin and biliary epithelium CKs, whereas fetal areas display a more developed phenotype, similar to that of mature hepatocytes. These data aid in understanding the ontogenesis of HBs and may be used in histopathological diagnosis.