Clinical, cytologic, and histologic features of a mammary micropapillary carcinoma in a dog

Mammary invasive micropapillary carcinoma is a rare variant of mammary carcinoma that was recently recognized in dogs. The cytologic features and biologic behavior of such neoplasms in dogs have not yet been widely discussed in the veterinary literature. We report the clinical, cytologic, and histologic features of a canine micropapillary carcinoma in a 13-year-old female mongrel dog. The mammary region presented with extreme local pain, severe edema and erythema, and multifocal epidermal ulceration, which is typical for an inflammatory mammary carcinoma. Fine-needle aspirates were highly cellular and consisted of individual cells and papillary cell clusters with characteristics of malignant epithelial cells. Histologic examination revealed neoplastic cells arranged in small papillae without fibrovascular cores, sometimes inside clear lymphatic spaces, indicating lymphovascular invasion. Regional lymph node evaluation revealed metastatic cells. Due to deteriorating clinical condition the dog was euthanatized 5 months after mastectomy. At necropsy, metastatic neoplastic mammary cells were found in popliteal and mediastinal lymph nodes, the right femoral biceps muscle, liver, heart, lungs, and urinary bladder. © 2013 American Society for Veterinary Clinical Pathology.

Alterações cromossômicas em células uroteliais esfoliadas de pacientes com história de carcinoma de células transicionais

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ganhos e perdas genômicas em momentos sucessivos do carcinoma urotelial de bexiga humana

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeitos citotóxicos e toxicogenômicos dos antineoplásicos cisplatina e gencitabina em células de carcinoma de bexiga

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genetic Instability Persists in Non-Neoplastic Urothelial Cells from Patients with a History of Urothelial Cell Carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cell cycle kinetics, apoptosis rates, DNA damage and TP53 gene expression in bladder cancer cells treated with allyl isothiocyanate (mustard essential oil)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

MRE11A and SKP2 genes are associated with the increased cytotoxicity induced by the synergistic effects of cisplatin and gemcitabine in bladder cancer cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga

Pós-graduação em Patologia - FMB

Bladder expression of CD cell surface antigens and cell-type-specific transcriptomes

Many cell types have no known functional attributes. In the bladder and prostate, basal epithelial and stromal cells appear similar in cytomorphology and share several cell surface markers. Their total gene expression (transcriptome) should provide a clear measure of the extent to which they are alike functionally. Since urologic stromal cells are known to mediate organ-specific tissue formation, these cells in cancers might exhibit aberrant gene expression affecting their function. For transcriptomes, cluster designation (CD) antigens have been identified for cell sorting. The sorted cell populations can be analyzed by DNA microarrays. Various bladder cell types have unique complements of CD molecules. CD9(+) urothelial, CD104(+) basal and CD13(+) stromal cells of the lamina propria were therefore analyzed, as were CD9(+) cancer and CD13(+) cancer-associated stromal cells. The transcriptome datasets were compared by principal components analysis for relatedness between cell types; those with similarity in gene expression indicated similar function. Although bladder and prostate basal cells shared CD markers such as CD104, CD44 and CD49f, they differed in overall gene expression. Basal cells also lacked stem cell gene expression. The bladder luminal and stromal transcriptomes were distinct from their prostate counterparts. In bladder cancer, not only the urothelial but also the stromal cells showed gene expression alteration. The cancer process in both might thus involve defective stromal signaling. These cell-type transcriptomes provide a means to monitor in vitro models in which various CD-isolated cell types can be combined to study bladder differentiation and bladder tumor development based on cell-cell interaction.

TWIST and p-Akt immunoexpression in normal oral epithelium, oral dysplasia and in oral squamous cell carcinoma

Objectives: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. Study design: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. Results: Kruskal-Wallis and Dunn's post tests revealed a significant difference in TWIST and p-Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson's correlation test. Conclusions: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages.

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

Background: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). Methods: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). Conclusion: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

Expression of calcium binding protein S100 A7 (psoriasin) in laryngeal carcinoma

Many studies have reported increased expression of S100 A7 (psoriasin) in neoplastic lesions. Among them are studies on breast carcinoma, bladder squamous cell carcinoma, skin tumors and oral cavity squamous cell carcinoma. The expression of S100 A7 has not been described for laryngeal cancer. Objective: This study aims to identify the expression of the calcium-binding protein S100 A7 and its correlation with squamous cell carcinomas of the larynx. Material and Methods: Specimens from 63 patients were submitted to immunohistochemistry testing with antibody S100 A7. Results were classified and compared. Results: The group with highly differentiated tumors had the highest treatment failure scores. Moderately differentiated tumors had higher treatment failure scores than poorly differentiated tumors. Higher scores were predominantly seen on stages I and II in moderately differentiated tumors, whereas score distribution was more homogeneous in advanced stage disease (III and IV). Regarding failure in treatment, the group scoring zero (3/4 complications: 75%) differed significantly from the remaining groups (13/59: 22%). Conclusions: S100 A7 marker was expressed in 93.7% of laryngeal cancer cases, with higher positive correlation rates in more differentiated tumors and significantly lower rates of treatment failure. Scores had no impact on survival rates.

Discrimination of Basal Cell Carcinoma and Melanoma from Normal Skin Biopsies in Vitro Through Raman Spectroscopy and Principal Component Analysis

Objective: Raman spectroscopy has been employed to discriminate between malignant (basal cell carcinoma [BCC] and melanoma [MEL]) and normal (N) skin tissues in vitro, aimed at developing a method for cancer diagnosis. Background data: Raman spectroscopy is an analytical tool that could be used to diagnose skin cancer rapidly and noninvasively. Methods: Skin biopsy fragments of similar to 2 mm(2) from excisional surgeries were scanned through a Raman spectrometer (830 nm excitation wavelength, 50 to 200 mW of power, and 20 sec exposure time) coupled to a fiber optic Raman probe. Principal component analysis (PCA) and Euclidean distance were employed to develop a discrimination model to classify samples according to histopathology. In this model, we used a set of 145 spectra from N (30 spectra), BCC (96 spectra), and MEL (19 spectra) skin tissues. Results: We demonstrated that principal components (PCs) 1 to 4 accounted for 95.4% of all spectral variation. These PCs have been spectrally correlated to the biochemicals present in tissues, such as proteins, lipids, and melanin. The scores of PC2 and PC3 revealed statistically significant differences among N, BCC, and MEL (ANOVA, p < 0.05) and were used in the discrimination model. A total of 28 out of 30 spectra were correctly diagnosed as N, 93 out of 96 as BCC, and 13 out of 19 as MEL, with an overall accuracy of 92.4%. Conclusions: This discrimination model based on PCA and Euclidean distance could differentiate N from malignant (BCC and MEL) with high sensitivity and specificity.

Morphological alterations and gene and protein expression profiling of bladder tumor cells after treatment with gemcitabine.

Chemical agents used in cancer therapy are associated with cell cycle arrest, activation or deactivation of mechanisms associated to DNA repair and apoptosis. However, due to the complexity of biological systems, the molecular mechanisms responsible for these activities are not fully understood. Thus, studies about gene and protein expression have shown promising results for understanding the mechanisms related to cellular responses and regression of cancer after chemotherapy. This study aimed to evaluate the gene and protein expression profiling in bladder transitional cell carcinoma (TCC) with different TP53 status after gemcitabine (1.56 μM) treatment. The RT4 (grade 1, TP53 wild type), 5637 (grade 2, TP53 mutated) and T24 (grade 3, TP53 mutated) cell lines were used. PCR arrays and mass spectrometry were used to analyze gene and protein expression, respectively. Morphological alterations were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results of PCR array showed that gemcitabine activity was mainly related to CDKN1A, GADD45A and SERTDA1 overexpression, and BAX overexpression only in the wild type TP53 cells. Mass spectrometry demonstrated that gemcitabine modulated the protein expression, especially those from genes related to apoptosis, transport of vesicles and stress response. Analyses using SEM and TEM showed changes in cell morphology independently on the cell line studied. The observed decreased number of microvillus suggests low contact among the cells and between cell and extracellular matrix; irregular forms might indicate actin cytoskeleton deregulation; and the reduction in the amount of organelles and core size might indicate reduced cellular metabolism. In conclusion, independently on TP53 status or grade of bladder tumor, gemcitabine modulated genes related to the cell cycle and apoptosis, that reflected in morphological changes indicative of future cell death.

Do patients benefit from routine follow-up to detect recurrences after radical cystectomy and ileal orthotopic bladder substitution?

The need for and intensity of follow-up to detect disease recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) remains a matter for debate.