Endocan may predict the presence of coronary slow flow and coronary artery disease.

OBJECTIVE: Coronary artery disease (CAD) is frequent, but coronary slow flow (CSF) is a less common cardiovascular disease with a significant risk of mortality and morbidity. Endocan is a proinflammatory glycopeptide that has been investigated in cardiovascular diseases as well as some inflammatory diseases in recent years. We planned to compare the levels of endocan in both CAD and CSF in a similar population and examine the relationship of endocan with additional clinical variables. MATERIALS AND METHODS: In the trial, we included 169 consecutive subjects having a coronary angiography indication. According to the results of coronary angiography, 58 people were included in the CAD group, 52 were in the CSF group, and 59 people were in the control group. The control group includes those who did not have any lesions in their epicardial coronary arteries. Thrombolysis in myocardial infarction (TIMI)-frame counts (TFC) were calculated for all patients. RESULTS: Notably, 2.6% of the population in our study had CSF. Both the CAD (555±223 pg/mL) and CSF (559±234 pg/mL) groups had higher endocan levels than the control group (331±252 pg/mL) (p<0.001). There were similar endocan levels between the CAD and CSF groups. Endocan levels were shown to be favorably associated with mean TFC (r=0.267; p0.001). Serum endocan levels (particularly those above 450 pg/mL) and the presence of hyperlipidemia were the most important predictors of both CAD and CSF. CONCLUSION: Endocan levels are higher in CAD and CSF patients than in those with normal coronary arteries.

Carcinoma of the rete testis: A rare testicular tumor.

Carcinoma of the rete testis is a rare malignant tumor which frequently occurs in middle-aged to older patients and has an aggressive biological behavior. We present the case of a 57-year-old man who presented with an ill-defined mass in the right testicle. The patient underwent a radical orchidectomy. Microscopic evaluation showed a neoplasm displaying a complex papillary-cystic architecture, infiltrating the testicular parenchyma. An in situ proliferation of neoplastic cells, with nuclear stratification and scanty cytoplasm was seen at the periphery, within the channels of the rete testis. The tumor infiltrated the tunica albuginea focally without disrupting it completely. Immunohistochemistry was positive for AE1/AE3, CK7, CK34ßE12, D2-40, and PAX8. Imaging studies presented no evidence of metastatic disease. These findings are those of a primary rete testis carcinoma. The transition between benign and neoplastic rete testis epithelium served as a helpful diagnostic clue. Metastatic carcinomas from other sites were considered in the differential diagnosis.

Epithelioid hemangioendothelioma of the parotid gland: A case report in an unusual location with a review of the literature.

Epithelioid hemangioendothelioma (EHE) is a malignant vascular tumor that usually affects the liver, lung, bone and deep soft tissues of the extremities or trunk. To our knowledge, only 3 cases in the parotid gland have been reported to date. We report a case of a 62-year-old woman who presented with a 1-year history of a slow-growing, painless mass over the left mandibular angle. Imaging studies showed a 2cm mass over the left parotid gland with peripheral calcifications. The patient underwent a superficial parotidectomy. Sections displayed neoplastic epithelioid cells with cytoplasmic vacuoles containing erythrocytes, surrounded by a myxohyaline stroma. Immunohistochemistry was positive for CD31, CD34, ERG, and factor VIII, but negative for cytokeratin AE1/AE3, CK7, EMA, SMA, and S100. The findings were those of an EHE involving the parotid gland. This case demonstrates an EHE in a rare location and emphasizes the need to consider this tumor when diagnosing uncommon soft tissue tumors of salivary glands.

Quantitative label-free mass spectrometry using contralateral and adjacent breast tissues reveal differentially expressed proteins and their predicted impacts on pathways and cellular functions in breast cancer.

Proteins play an essential role in the biological processes associated with cancer. Their altered expression levels can deregulate critical cellular pathways and interactive networks. In this study, the mass spectrometry-based label-free quantification followed by functional annotation was performed to investigate the most significant deregulated proteins among tissues of primary breast tumor (PT) and axillary metastatic lymph node (LN) and corresponding non-tumor tissues contralateral (NCT) and adjacent (ANT) from patients diagnosed with invasive ductal carcinoma. A total of 462 proteins was observed as differentially expressed (DEPs) among the groups analyzed. A high level of similarity was observed in the proteome profile of both non-tumor breast tissues and DEPs (n = 12) were mainly predicted in the RNA metabolism. The DEPs among the malignant and non-tumor breast tissues [n = 396 (PTxNCT) and n = 410 (LNxNCT)] were related to pathways of the LXR/RXR, NO, eNOS, eIF2 and sirtuins, tumor-related functions, fatty acid metabolism and oxidative stress. Remarkable similarity was observed between both malignant tissues, which the DEPs were related to metastatic capabilities. Altogether, our findings revealed differential proteomic profiles that affected cancer associated and interconnected signaling processes. Validation studies are recommended to demonstrate the potential of individual proteins and/or pathways as biological markers in breast cancer. SIGNIFICANCE: The proteomic analysis of this study revealed high similarity in the proteomic profile of the contralateral and adjacent non-tumor breast tissues. Significant differences were identified among the proteome of the malignant and non-tumor tissue groups of the same patients, providing relevant insights into the hallmarks, signaling pathways, biological functions, and interactive protein networks that act during tumorigenesis and breast cancer progression. These proteins are suggested as targets of relevant interest to be explored as potential biological markers related to tumor development and metastatic progression in the breast cancer disease.

Expression of PDK1 in malignant pheochromocytoma as a new promising potential therapeutic target.

PURPOSE: Phosphoinositide-dependent kinase 1 (PDK1) is highly expressed in many solid tumors. And several studies have demonstrated that PDK1 has been an emerging and promising target for anti-cancer therapies. However, the role of PDK1 has not been studied so far in malignant pheochromocytoma (PCC). METHODS: In this study, immunohistochemical staining was performed to investigate the protein level of PDK1 in 63 PCC tissue samples, of which 49 were benign and 14 were malignant. In addition, we evaluated the effect of inhibition of PDK1 with siRNA on cell growth, apoptosis and invasive capacity in PC12 cells and identified the underlying mechanisms. RESULTS: We found that PDK1 was overexpressed in malignant PCC tissues, and knockdown of PDK1 with siRNA significantly inhibited cell proliferation, increased apoptosis induction, and attenuated cell migration and invasive capacity in PC12 cells. We also showed that knockdown of PDK1 significantly reduced the phosphorylation of Akt at threonine 308 (p-Akt T308) but did not alter the serine phosphorylation of Akt on the S473 site (p-Akt S473). Furthermore, we found that the p-Akt expression was noticeably decreased after knockdown of PDK1, but the t-Akt expression did not show a significant decrease. CONCLUSION: We have demonstrated for the first time that PDK1 is overexpressed in human malignant PCC and plays an important role in the malignant biological behaviors of PC12 cell. Specifically, we have revealed that knockdown of PDK1 could attenuate activation of the Akt signaling. These data suggest that PDK1 could be a new promising potential therapeutic target in human cancer treatment for malignant PCC.

THE CANONICAL WNT PATHWAY IN GASTRIC CARCINOMA.

BACKGROUND: It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. AIM: To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. METHOD: The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3ß, axin, CK1, ubiquitin, cyclin D1 and c-myc. RESULTS: There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. CONCLUSION: The canonical WNT pathway is involved in gastric carcinoma.

The canonical wnt pathway in gastric carcinoma / Via canônica do wnt no carcinoma gástrico

ABSTRACT Background : It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. Aim : To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. Method : The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3β, axin, CK1, ubiquitin, cyclin D1 and c-myc. Results : There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. Conclusion: The canonical WNT pathway is involved in gastric carcinoma.

RESUMO Racional : Acredita-se que a via Wnt é uma das mais importantes da sinalização envolvidas na carcinogênese gástrica. Objetivos : Analisar a expressão das proteínas das vias Wnt canônicas e não-canônicas no carcinoma gástrico e relacionar sua expressão com as variáveisclinicopatológicas. Método : Foram coletadas 72 amostras de carcinoma gástrico, e áreas representativas do tumor foram selecionadas para o Tissue Microarray. Imunoistoquímica foi realizada para avaliar a expressão de Wnt-5a, FZD5, GSK3β, axina, CK1, ubiquitina, ciclina D1 e c-myc. Resultados : Houve diferenças significativas para a expressão de ubiquitina no citoplasma e núcleo para tumores moderadamente e bem diferenciados (p=0,03) e para aqueles do tipo intestinal da classificação de Lauren (p=0,03). A expressão negativa da proteína c-myc no citoplasma foi relacionada aos tumores intestinais de Lauren (p=0,028). A expressão positiva de CK1 no citoplasma das células neoplásicas foi relacionada a tumores com margens cirúrgicas livre de envolvimento neoplásico (p=0,03). A expressão positiva da proteína ciclina D1 foi maior nos tumores dos homens (p=0,03). Não houve relação da expressão positiva ou negativa das proteínas Wnt-5a e FZD5 no citoplasma ou núcleo com quaisquer variáveis clinicopatológicas. O mesmo foi observado para GSK3β e Axin. Conclusões : A relação da expressão das proteínas da via canônica com as variáveis epidemiológicas e tumorais sugere sua participação na carcinogênese gástrica. Por outro lado, a ausência da relação das expressões das proteínas da via não-canônica sugere sua não participação na carcinogênese gástrica.

Moesin Involvement in Oral Carcinogenesis of the Lower Lip.

BACKGROUND/AIM: This study analyzed moesin immunoexpression in 91 lip squamous cell carcinomas and its influence in patients' prognosis. MATERIALS AND METHODS: Moesin immunoexpression was evaluated at the invasive tumor front by a semi-quantitative score method. The association of moesin with the clinicopathological variables was analyzed by the Chi-square test, the survival rates were calculated by Kaplan-Meier and the survival curves compared using the log-rank test. RESULTS: The expression of moesin was strong at the invasive tumor front and weak/negative in differentiated cells such as keratin pearls. There was no association between moesin expression and the clinicopathological variables, but there was a tendency for patients with lip cancer and strong moesin expression to have lower 5- and 10-year overall and disease-free survival rates. CONCLUSION: Our results confirm the participation of moesin in oral carcinogenesis and suggest that this protein can influence the survival rates of patients with lip squamous cell carcinoma.

Immunohistochemical expression of Galectin-3 in canine tumors

Galectin-3 (Gal-3) is a protein expressed by both normal and neoplastic cells. It participates in several biological processes such as cell proliferation, cell adhesion, apoptosis, tissue remodeling, and angiogenesis. Although it is known to serve as a valuable prognostic marker in several types of human cancer, there are few reports about its applicability as a marker in the veterinary oncology literature. The aim of the present study was to characterize Gal-3 expression in different types of canine tumors. Fifty-three tissue samples from 22 histologically different types of canine tumors were immunohistochemically evaluated for Gal-3 expression. Variations in the percentage of Gal-3-positive cells, localization of Gal-3 protein, and percentage of Gal-3-positive fibroblasts were observed. These preliminary results showed variable expression of Gal-3 among canine tumors. Further studies are needed in order to investigate the potential of this protein as a prognostic marker and a therapeutic target.

Immunohistochemical expression of Galectin-3 in canine tumors

Galectin-3 (Gal-3) is a protein expressed by both normal and neoplastic cells. It participates in several biological processes such as cell proliferation, cell adhesion, apoptosis, tissue remodeling, and angiogenesis. Although it is known to serve as a valuable prognostic marker in several types of human cancer, there are few reports about its applicability as a marker in the veterinary oncology literature. The aim of the present study was to characterize Gal-3 expression in different types of canine tumors. Fifty-three tissue samples from 22 histologically different types of canine tumors were immunohistochemically evaluated for Gal-3 expression. Variations in the percentage of Gal-3-positive cells, localization of Gal-3 protein, and percentage of Gal-3-positive fibroblasts were observed. These preliminary results showed variable expression of Gal-3 among canine tumors. Further studies are needed in order to investigate the potential of this protein as a prognostic marker and a therapeutic target.(AU)

Comparison of Myocyte Enhancer Factor 2B Versus Other Germinal Center-associated Antigens in the Differential Diagnosis of B-Cell Non-Hodgkin Lymphomas.

Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Limited data exists concerning its expression in B-cell lymphomas, and comparison with other GC-associated antigens is lacking. Its role in the differential diagnosis of B-cell lymphomas, particularly in the distinction of follicular lymphoma (FL) versus marginal zone lymphoma (MZL), remains to be determined. We evaluated MEF2B expression, in comparison with additional GC markers, LIM domain-only transcription factor 2 (LMO2), and human GC-associated lymphoma (HGAL), in a variety of B-cell lymphomas, with particular emphasis on their utility in differentiating FL from MZL. MEF2B was positive in all FL and Burkitt lymphomas, 8/9 mantle cell lymphomas, 2/24 splenic MZL, 1/10 chronic lymphocytic leukemia/small lymphocytic lymphomas, and 38/44 diffuse large B-cell lymphoma (DLBCL), but was negative in all extranodal MZL of mucosa-associated lymphoid tissue, nodal MZL, and B-lymphoblastic lymphomas. Focusing on low-grade FL versus MZL, MEF2B was 100% sensitive and 95% specific for FL, which was similar to BCL6, but superior to LMO2 (sensitivity 87%, specificity 86%) and HGAL (sensitivity 97%, specificity 86%). Importantly, MEF2B was positive in 4/4 FL with plasmacytoid differentiation, which were CD10, only weakly BCL6, and included 1 case that lacked both LMO2 and HGAL expression. MEF2B was positive in 22/25 (88%) GC-type DLBCL, but was also positive in 16/19 (61%) non-GC-type DLBCL. MEF2B shows superior sensitivity and specificity than LMO2 and HGAL in the differential diagnosis of FL versus MZL and is particularly useful in FL with plasmacytoid differentiation, which may have morphologic and immunophenotypic overlap with MZL. MEF2B, however, is not specific for GC-derived B-cell lymphomas as it is also apparently positive in most mantle cell lymphoma and many non-GC-type DLBCL.

Evidence of progenitor cells in the adult human cochlea: sphere formation and identification of ABCG2.

OBJECTIVES: The aim of this study was to search for evidence of stem or progenitor cells in the adult human cochlea by testing for sphere formation capacity and the presence of the stem cell marker ABCG2. METHODS: Cochleas removed from patients undergoing vestibular schwannoma resection (n=2) and from brain-dead organ donors (n=4) were dissociated for either flow cytometry analysis for the stem cell marker ABCG2 or a sphere formation assay that is widely used to test the sphere-forming capacity of cells from mouse inner ear tissue. RESULTS: Spheres were identified after 2-5 days in vitro, and the stem cell marker ABCG2 was detected using flow cytometric analysis after cochlear dissociation. CONCLUSIONS: Evidence suggests that there may be progenitor cells in the adult human cochlea, although further studies are required.

Evidence of progenitor cells in the adult human cochlea: sphere formation and identification of ABCG2

OBJECTIVES: The aim of this study was to search for evidence of stem or progenitor cells in the adult human cochlea by testing for sphere formation capacity and the presence of the stem cell marker ABCG2. METHODS: Cochleas removed from patients undergoing vestibular schwannoma resection (n=2) and from brain-dead organ donors (n=4) were dissociated for either flow cytometry analysis for the stem cell marker ABCG2 or a sphere formation assay that is widely used to test the sphere-forming capacity of cells from mouse inner ear tissue. RESULTS: Spheres were identified after 2-5 days in vitro, and the stem cell marker ABCG2 was detected using flow cytometric analysis after cochlear dissociation. CONCLUSIONS: Evidence suggests that there may be progenitor cells in the adult human cochlea, although further studies are required.

Expression of anoctamin 1 is associated with advanced tumor stage in patients with non-small cell lung cancer and predicts recurrence after surgery.

PURPOSE: Anoctamin 1 (ANO1), a recently identified calcium-activated chloride channel, has been found to have a critical role in tumorigenesis and tumor progression in several types of cancer. However, its role in non-small cell lung cancer (NSCLC) remains to be elucidated. In this study, we evaluated the utility of ANO1 as a prognostic marker. PATIENTS AND METHODS: ANO1 expression was detected in tumor tissues and paraneoplastic tissues of I-IV stage NSCLC patients who received surgical treatment by using immunohistochemical and quantitative RT-PCR analyses. Epidermal growth factor receptor (EGFR) was investigated using immunohistochemistry. Then the TNM stage of the tumor samples was assessed and patients were followed up for developing recurrence. RESULTS: ANO1 expression was significantly increased in NSCLC tumor tissues compared to the paraneoplastic tissues at both RNA and protein level. In addition, ANO1 overexpression was correlated with the high expression of EGFR and led to an advanced tumor stage. And also high ANO1 expression was significantly correlated with high recurrence rate at 1-year follow-up. CONCLUSIONS: ANO1 overexpression associated with the high expression of EGFR can be a predictive marker of recurrence after surgery in NSCLC patients.

[Immunohistochemical assessment of HER2 expression in gastric cancer. A clinicopathologic study of 93 cases]. / Evaluación por inmunohistoquímica de la expresión del HER2 en cáncer gástrico. Estudio clínico-patológico de 93 casos.

BACKGROUND: Gastric cancer in Mexico is ranked third in both males and females. Most patients present clinically with advanced disease and treatment options are sparse. HER2 overexpression in gastric cancer is related to poor outcome. Immunohistochemical testing for HER2 is becoming the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab. OBJECTIVES: To determine the frequency of HER2 overexpression in patients with gastric cancer in the Hospital de Oncología del Centro Médico Nacional, Siglo XXI and its association with other histopathological findings. MATERIAL AND METHODS: Patients with gastric cancer who underwent surgery between March 12, 2006-August 31, 2011, were enrolled in this retrospective study. Diagnosis was confirmed by review of slides and immunohistochemistry with anti-HER2 antibody was performed. Scoring was done by Hoffman scoring system. Medical records were evaluated. RESULTS: Ninety-three patients were included in the study, with 43 (46.2%) male and 50 (53.7%) female patients. The median age was 64 years. HER2-positive tumours were identified in 6 patients (6.45%) and located most frequently in the proximal stomach. There was no difference in HER2 overexpression in relation to age, gender or histologic type. CONCLUSION: In our study, about 7% of patients with gastric cancer were HER2-positive on immunohistochemistry.

Proteomic assessment of colorectal cancers and respective resection margins from patients of the Amazon state of Brazil.

Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is referred to as the resection margin. Our analysis employed an 8-plex iTRAQ to label four adenocarcinoma biopsies and their corresponding resection margins at 5cm; our results disclose fifty-six proteins as being differentially abundant. These proteins are mainly involved in energetic metabolism (e.g. S100 calcium binding protein A11), cell migration (e.g. transgelin), formation of the cytoskeleton (e.g. profilin 1) and degradation of extracellular matrix (e.g. carbonic anhydrase 2). A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell. Taken together, our results highlight proteins related to invasion, cell proliferation, and linked to the metastasis of colorectal cancer in tumor tissue. Finally, we argue that the expression patterns revealed in our comparison helps shed light on the development of more effective surgical strategies and add to the comprehension of this disease. BIOLOGICAL SIGNIFICANCE: Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is also referred to as the resection margin. In this regard, resection margins pose as a treasure trove for investigating the molecular characteristics of the tumorigenesis process. While most studies focus on comparing cancer versus control tissue, this study contrasts the proteomic profiles of colorectal cancer biopsies with their corresponding resection margin at 5cm apart. Our analysis employed an 8-plex iTRAQ labeling and a 4-step offline MudPIT online with a Velos. A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell.

TNFα-Induced Mucin 4 Expression Elicits Trastuzumab Resistance in HER2-Positive Breast Cancer.

PURPOSE: Although trastuzumab administration improved the outcome of HER2-positive breast cancer patients, resistance events hamper its clinical benefits. We demonstrated that TNFα stimulation in vitro induces trastuzumab resistance in HER2-positive breast cancer cell lines. Here, we explored the mechanism of TNFα-induced trastuzumab resistance and the therapeutic strategies to overcome it. EXPERIMENTAL DESIGN: Trastuzumab-sensitive breast cancer cells, genetically engineered to stably overexpress TNFα, and de novo trastuzumab-resistant tumors, were used to evaluate trastuzumab response and TNFα-blocking antibodies effectiveness respectively. Immunohistochemistry and antibody-dependent cell cytotoxicity (ADCC), together with siRNA strategy, were used to explore TNFα influence on the expression and function of its downstream target, mucin 4 (MUC4). The clinical relevance of MUC4 expression was studied in a cohort of 78 HER2-positive breast cancer patients treated with adjuvant trastuzumab. RESULTS: TNFα overexpression turned trastuzumab-sensitive cells and tumors into resistant ones. Histopathologic findings revealed mucin foci in TNFα-producing tumors. TNFα induced upregulation of MUC4 that reduced trastuzumab binding to its epitope and impaired ADCC. Silencing MUC4 enhanced trastuzumab binding, increased ADCC, and overcame trastuzumab and trastuzumab-emtansine antiproliferative effects in TNFα-overexpressing cells. Accordingly, administration of TNFα-blocking antibodies downregulated MUC4 and sensitized de novo trastuzumab-resistant breast cancer cells and tumors to trastuzumab. In HER2-positive breast cancer samples, MUC4 expression was found to be an independent predictor of poor disease-free survival (P = 0.008). CONCLUSIONS: We identified TNFα-induced MUC4 expression as a novel trastuzumab resistance mechanism. We propose MUC4 expression as a predictive biomarker of trastuzumab efficacy and a guide to combination therapy of TNFα-blocking antibodies with trastuzumab. Clin Cancer Res; 23(3); 636-48. ©2016 AACR.

Parotid Cystic Lesion in Amelanotic Malignant Melanoma.

A 60-year Brazilian woman, presented with an enlarged lymph node in the neck for one year, and a superficial nonulcerated lesion was observed in the scalp. Fine needle aspiration and biopsy of the lymph node revealed amelanocytic metastasis, and immunohistochemistry study showed Melan-A/ Mart-1 antigen (clone A103 and S-100 protein). The entire suspected area of the scalp was further resected and an amelanotic melanoma without angiolymphatic invasion was diagnosed. Ultrasonography and PET-computed tomography showed hypermetabolic cystic area in the right parotid. Furthermore, aspiration biopsy and surgical samples from parotid cyst confirmed the malignant amelanotic melanoma. Cystic metastases are scarcely reported in parotid gland, and can pose diagnostic challenges.

Ulceration in bladder cancer associates with extravesical disease, independent of cell cycle, or hypoxia pathways status: Integrating gross morphology and expression profiles in cystectomies.

OBJECTIVE: Ulceration is common in bladder tumors, but its prognostic role, although intuitive, is not established. We aim to explore the presence of gross ulceration and its relationship with other morphological and biological features classically associated with extravesical disease, in patients submitted to radical cystectomy. METHODS: Tumor size and morphology were noted on 101 cystectomy patients (2000-2010). Papillary, exophytic, and vegetant tumors were grouped as "papillary" and solid/nodular, ulcerated and infiltrative as "nonpapillary." Ulceration was noted grossly in every case as a binary parameter, regardless of morphology. Immunohistochemistry was performed for hypoxia (hypoxia-inducible factor-1α and vascular endothelial growth factor), and cell cycle proteins (pRb, p53, and cyclin D1). RESULTS: Mean age was 66.7 year, male:female ratio was 2:1, 20 patients received bacillus Calmette-Guerin and 10 neoadjuvant chemotherapy. Upstaging rate was 56.4%. Ulcerated lesions presented mostly as nonpapillary and nonorgan confined (nOC), whereas nonulcerated tumors were often papillary and organ confined (OC). Tumor size was smaller in nonpapillary tumors (P = 0.002), but did not associate with altered hypoxia or cell cycle expressions. pRb and cyclin D1 loss and p53 overexpression were more frequent in ulcerated and non-OC tumors as did the phenotype vascular endothelial growth factor-negative/hypoxia-inducible factor-1α-low (P<0.001). On a multivariate model, ulceration was an independent predictor of non-OC and extravesical disease. CONCLUSION: Patients with ulcerated tumors were often staged with extravesical disease, independent of other morphologic and biological features known to affect prognosis. Prospective studies are needed to confirm the predictive value of tumor ulceration at cystoscopy, which could improve patient stratification for neoadjuvant chemotherapy.

What gastric cancer proteomic studies show about gastric carcinogenesis?

Gastric cancer is a complex, heterogeneous, and multistep disease. Over the past decades, several studies have aimed to determine the molecular factors that lead to gastric cancer development and progression. After completing the human genome sequencing, proteomic technologies have presented rapid progress. Differently from the relative static state of genome, the cell proteome is dynamic and changes in pathologic conditions. Proteomic approaches have been used to determine proteome profiles and identify differentially expressed proteins between groups of samples, such as neoplastic and nonneoplastic samples or between samples of different cancer subtypes or stages. Therefore, proteomic technologies are a useful tool toward improving the knowledge of gastric cancer molecular pathogenesis and the understanding of tumor heterogeneity. This review aimed to summarize the proteins or protein families that are frequently identified by using high-throughput screening methods and which thus may have a key role in gastric carcinogenesis. The increased knowledge of gastric carcinogenesis will clearly help in the development of new anticancer treatments. Although the studies are still in their infancy, the reviewed proteins may be useful for gastric cancer diagnosis, prognosis, and patient management.