Heterogeneous vascular patterns in renal cell carcinomas.

The present study proposes a classification of renal cancer tumor blood vessels according to their morphology and maturation grade. We identified four vascular patterns: reticular, diffuse, fasciculated and trabecular. The reticular pattern was present in 63% of cases, being characterized by the predominance of mature CD34+/SMAct+ tumor vessels, highly interconnected. For this pattern, 74% of cases had vascular invasion, and a significant correlation was observed between tumor grade and immature state of tumor vessels (p = 0.022). The diffuse pattern was observed in 23% of cases and was characterized by non-interconnected vessels predominantly of mature CD34+/SMAct+ type and vascular invasion in 64% of cases. Only 8% of cases, had a fasciculate model of vessels distribution, all of them being of mature type, located in the connective axis of papillary renal tumors. For this pattern vascular invasion was found in 50% of cases. In 6% of cases a trabecular pattern was observed and the lowest rate of vascular invasion was registered. We defined here four distinct vascular patterns in renal cell carcinomas showing a strong impact on vascular invasion. A complete morphological and molecular characterization of tumor vessels would be beneficial in elucidating the mechanisms that underlie the ineffectiveness of antiangiogenic/antitumor therapies.

[Immunohistochemical study of the role of mast cells and macrophages in the process of angiogenesis in the atherosclerotic plaques in patients with metabolic syndrome].

OBJECTIVE: to analyze the histotopographic distribution of neogenic vessels, the degree of mast cell degranulation, the expression of markers of macrophages in different types of plaques in different stages and in different arterial vessels in patients with atherosclerosis and in those with metabolic syndrome associated with atherosclerosis and to establish the role of mast cells and macrophages in the development of stages of atherosclerosis along with their diagnostic and prognostic value. MATERIAL AND METHODS: Fragments of the thoracic and abdominal aorta, middle cerebral, carotid, renal, and iliac, and vertebral arteries from 34 persons who had died from atherosclerosis (n=17) and atherosclerotic complications due to metabolic syndrome (n=17) were examined. The investigators employed standard techniques, such as hematoxylin-eosin or orcein staining; silver impregnation. They used immunohistochemical staining with anti-mast cell tryptase (anti-MCT) for the determination of mast cells, the specific markers CD68 for macrophages, and CD105 (endoglin) for neogenic vessels. RESULTS: The immunohistochemical technique is effective in identifying mast cells, macrophages, and neogenic vessels in atherosclerotic plaques. They were found in many types of atherosclerotic plaques, advantium, and subendothelial layers in the immediate vicinity of the plaques. There was a statistical correlation between the types of plaques and clinical data, which is of importance in elucidating the specific features of the pathogenesis of atherosclerosis in patients with metabolic syndrome. CONCLUSION: CD105 is a sensitive marker for neogenic endothelial cells, an effective indicator of microvascular activation and proliferation in the atherosclerotic plaques. Neovascularization in the plaques frequently begins in the intima, progresses, and gives rise to their further destabilization. Anti-MCT staining used to reveal mast cells and CD68 for macrophages can elucidate the important patterns of development of atherosclerosis and its complications in patients with metabolic disturbances.

Circular anastomotic experimental fibrin sealant protection in deep colorectal anastomosis in pigs in a randomized 9-day survival study.

PURPOSE: The reported rate of clinically apparent anastomotic leakage (AL) in a low anterior resection of the rectum (LAR) (≤7 cm from the anal verge) using a circular double-stapled anastomosis (CDSA) without defunctioning stoma is up to 37.5 %. Since AL may result in life-threatening peritonitis, sepsis, and multiple organ failure, LAR and CDSA are regularly combined with defunctioning stoma. Accordingly, we now evaluated whether LAR and CDSA without defunctioning stoma but with extraluminal anastomotic application of an experimental fibrin sealant reduce the AL rate. This might prevent humans from defunctioning stoma increasing quality of life and decreasing surgical costs. METHODS: Forty 8-week-old pigs underwent LAR and CDSA in an end-to-end technique (descendo-rectostomy). Animals were randomized into a therapy and control group (gr.). The therapy gr. (n = 20) received an additional extraluminal circular application of an experimental fibrin sealant to the anastomosis. The objective was to assess the incidence of clinically apparent and non-clinically apparent leakage through the ninth postoperative day. Double-contrast barium CT radiographs of the colorectal region were performed on the ninth postoperative day or earlier, in case there were clinical signs of AL. All remaining animals were sacrificed on the ninth postoperative day and the anastomotic region was histopathologically analyzed. In case of earlier diagnosed AL, animals were sacrificed immediately. Blood samples were taken for complete blood count, chemistry, and coagulation profile prior to surgery and on the first, third, fifth, seventh, and ninth postoperative day. RESULTS: A circular extraluminal anastomotic application of an experimental fibrin protection decreased the rate of clinically and non-clinically apparent AL from 20 % (n = 4) in the control group to 5 % (n = 1) in the treatment group. Ulcerations were also observed in both gr. (control gr.-5 animals, therapy gr. -3 animals). All animals with AL showed necrosis surrounding the hole at the anastomoses. Three additional animals had a full wall defect at the anastomotic region that was blocked by the experimental fibrin sealant. The fibrin sealant was present at necropsy in all treated animals. CONCLUSION: Circular anastomotic protection with the experimental fibrin sealant blocked anastomotic full wall defects, preventing peritonitis and significantly reducing the AL rate from 25 to 5 %.

Mast cell phenotype in benign and malignant tumors of the prostate.

The molecular phenotypic heterogeneity of mast cells (MCs) makes them attractive as potential therapeutic targets in anti-cancer adjuvant therapy. Mast cell aggregations observed in tumors suggested their involvement in tumor pathogenesis. Despite several studies using mast cell tryptase, MCs' involvement in the progression of prostate tumors has not been demonstrated. The aim of our study was to identify and quantify the phenotypic heterogeneity of MCs in prostate lesions. Our study included 7 cases of normal prostate, 25 cases of benign epithelial hyperplasia and 64 cases of prostate carcinoma. MCs were immunohistochemically assessed using three markers: tryptase, chymase and CD117. Two immunophenotypes of MCs were identified in benign lesions: tryptase+/CD117+/chymase- and tryptase-/chymase+/CD117+, located in peritumoral areas. Intratumoral MC phenotype of malignant lesions was characterized by tryptase+/chymase+/CD117+, while in the peritumoral areas three different MCs phenotypes were identified: tryptase+/chymase+/CD117-, tryptase+/CD117+/chymase- and chymase+/CD117+/tryptase-. Our results suggest the correlation of chymase positive MCs of the peritumoral areas and CD117 positive MCs of the intratumoral areas with tumor grade.

Estrogen receptor alpha polymorphisms: correlation with clinicopathological parameters in breast cancer.

Polymorphisms in estrogen receptor alpha gene (ESR1) have been previously associated with breast cancer risk; however, the results were not fully consistent. Our purpose was to study interactions between common genotypes in ESR1, breast cancer risk and tumor phenotypes. 6 ESR1 single nucleotide polymorphisms (SNPs) were genotyped in 103 breast cancer patients and 90 controls using hybridization probes; the genotypes were correlated with known prognostic factors for breast cancer and 5 years-follow up data. To assess estrogen and progesterone receptors (ER, PR) and HER2/neu expressions, immunohistochemistry was performed. Our results showed that rs3798577 was significantly associated with the risk of breast cancer, the common allele C conferring susceptibility (p-trend=4 x 10(-5)); rs3798577 was also correlated with PR expression (p=0.01), but not with ER expression; rs2228480 (p=0.047) and rs1801132 (p=0.02) were associated with the age at diagnosis; rs1801132 was correlated with hypercholesterolemia (p=0.003) and increased BMI (body mass index) (p=0.01); rs2234693 showed a low significant association (p=0.042) with the tumor grade; rs3798577 was correlated with disease-free survival (p=0.05), allele C conferring increased risk for relapses, but it reached not statistical significance after adjustments. In conclusions, we identified four genotypes significantly correlated with either the risk or some tumor characteristics, suggesting that the main selection criteria of the investigated SNPs (frequency and the position in modulating domains of the gene) are pertinent instruments for establish correlations between the gene structure and the tumor phenotype.

The diagnostic value of cytokeratins expression in the renal parenchyma tumors.

Renal carcinomas are a heterogeneous group of tumors, difficult to classify and identify precisely. Since their prognosis depends very much upon their type, precise diagnosis might mean the difference between therapeutic success and patient death. Cytokeratins are particularly useful for the identification of the epithelial nature of the tumors, because their expression is maintained even in poorly differentiated tumors. Monoclonal cytokeratins such as CK7 and CK20 stain different components of the renal tubular system and are a useful duo for the identification of the origin of the different tumors that might arise in the kidney. Along with polyclonal cytokeratins such as AE1/AE3 and high molecular weight cytokeratin antibodies (34betaE12, Cam 5.2), epithelial membrane antigen (EMA) and vimentin, they are included in every diagnostic panel for renal tumors. We have selected 138 renal parenchyma tumor specimens, performed morphological diagnosis and then stained them with polyclonal cytokeratin antibody AE1/AE3, and monoclonal antibodies to CK7 and CK20. AE1/AE3 was expressed in 61.7% of the renal parenchyma tumors, with high intensity and percentage of positive cases in the papillary carcinomas (100%), and with rare and weakly positive cells in chromophobic cells carcinomas, clear cells carcinomas and sarcomatous carcinomas. CK7 was positive in 68% of the renal parenchyma tumors, with positive reaction in 100% of the cases of chromophobic cells and sarcomatous carcinomas. Clear cells carcinomas had the less percentage of positive cells, whereas papillary carcinomas were positive in seven out of eight cases. No difference in the staining pattern was noticed between type I and type II papillary carcinomas. CK20 was negative in all cases studied.

Angiogenesis in the human thymoma assessed by subclassification of tumor-associated blood vessels and endothelial cells proliferation.

The prognostic value of tumor-associated angiogenesis is still a subject of debate. As microvascular density and the expression of different growth factors were not demonstrated to be good predictors of the response to antiangiogenic and antivascular therapy, there is a strong need to search for more sensitive markers. In the present study we evaluated by double immunohistochemical staining the profile of tumor-associated blood vessels and the rate of endothelial cell proliferation in patients with thymoma (n=38). Results were compared with specimens of normal thymus and from patients with myasthenia gravis. We found a significant increase in the number of immature and intermediate blood vessels in the tumor area of thymoma, regardless the histological type of the tumor. Proliferating endothelial cells were found in 15 cases, and co-expression of Ki67 and CD34 had the highest value in immature vessels. Both blood vessel type and endothelial cell proliferation significantly correlated with invasive thymoma. Based on these findings, it can be assumed that the type of tumor-associated vessel together with endothelial cell proliferation are useful predictors of invasion, immature and intermediate vessels can be targeted with antivascular drugs and endothelial cell proliferation could be used as a good predictor of the response to antiangiogenic therapy.

Diagnostic and clinical significance of D2-40 expression in the normal human thymus and thymoma.

Human thymus development and thymoma behavior remain elusive, in spite of many acquisitions in the field in last decades. In the present paper, we analyzed the immunohistochemical expression of D2-40 in the normal human thymus and thymoma. In both fetal and postnatal normal thymus, we found a strong expression of D2-40 in the subcapsular and cortico-medullary epithelial cells, and lack of expression in the thymus of involution. These findings support a role for podoplanin in the proliferation of some subtypes of epithelial cells of the normal thymus stroma. In thymoma, the expression of D2-40 was detected in neoplastic cells in 18 from 26 cases (69.23%). No correlation was found between D2-40 expression and histological types of thymoma, but strong correlation was noticed with tumor stage. Based on these results, it is suggested that D2-40 expression is a good predictor of invasion and can be considered as a potential target for therapy in selected cases.

Clinical significance of Her2/neu overexpression in urothelial carcinomas.

HER2/neu is a defective transmembrane tyrosine kinase receptor, homologue to the epidermal growth factor receptor, showing overexpression in a large variety of tumor cells. There are no studies published so far regarding HER2/neu overexpression and sensitivity of the urothelial tumors of the urinary bladder to anti-HER2/neu therapy. There are a relatively high number of articles in the literature referring to HER2/neu expression in urothelial tumors of the urinary bladder, but only two of them had investigated HER2/neu expression in patients with urothelial tumors of the upper urinary tract. We have studied HER2/neu overexpression in 59 patients with urothelial carcinomas of the urinary tract by immunohistochemistry. Normal urothelium and the elements of the neighboring renal parenchyma were negative. Out of the 59 cases of urothelial carcinomas, 38 were negative (0 and +1) and 21 were positive: eight were moderately and 13 were intensely positive (+2 and +3). The percentage of positive cases was 35.59%. The negative cases were mostly well-differentiated, G1 tumors, no matter the T-tumor stage. Most of the cases were diagnosed as papillary or, rarely, infiltrative. There is no correlation between HER2/neu overexpression and the tumor stage. The same was true for the lymph node status. The expression intensity, however, was significantly correlated with the differentiation grade. Overexpression was most likely present in tumors with high differentiation grade (p<0.05).

Immunohistochemical expression and significance of epidermal growth factor receptor (EGFR) in breast cancer.

Breast cancer is a heterogeneous disease that includes several molecular types, characterized by the expression profile of sex hormone receptors, HER2 protein, cytokeratin 5, p53, and Bcl-2. EGFR is an additional marker predominantly expressed by basal-like carcinoma, but its significance in the other types is not completely understood. The aim of this study was to analyze the immunohistochemical expression of EGFR and its relationships with other factors of prognosis. There were investigated benign lesions and 84 cases with invasive breast carcinoma that were submitted first to the molecular classification. Next, we performed the staining for EGFR and two patterns of the final product of reaction were described. EGFR expression was found in 41.66% of the cases with basal-like carcinoma, in 50% of the cases with luminal B carcinoma, and in 21.42% of the cases with HER2 overexpression. A significant correlation was found between EGFR expression and degree of differentiation and distant metastasis. No significant correlation was found with the lymph node status, excepting for the basal-like carcinoma in which an inverse correlation was noticed. Our results suggest that EGFR expression by tumor cells of the breast cancer defines a specific subset of tumors with poor prognosis and potential resistance to the adjuvant therapy.

Unusual renal carcinoma with a double component: case report and review of the literature.

The authors report a rare case of a 60-year-old man who had in his left kidney a tumor with two distinct components: a tubulo-papillary pattern and an extensive high-grade squamous cell carcinoma. The literature concerning this subject will be also reviewed.

Identification of lymphatic vessels and prognostic value of lymphatic microvessel density in lesions of the uterine cervix.

Incomplete characterization of the uterine cervix cancer from molecular point of view represents the main problem for the use of a proper therapy in this disease. Few data are available about D2-40 expression in lymphatic endothelial cells and also in tumor cells from uterine cervix cancer. The aim of the present work was to study the involvement of lymphatics in prognosis and tumor progression of the uterine cervix lesions. We used D2-40 immunostaining to highlight lymphatic vessels from squamous cell metaplasia (n=17), cervical intraepithelial neoplasia (n=11), carcinoma in situ (n=3), microinvasive carcinoma (n=4) and invasive carcinoma (n=19) using Avidin-Biotin technique (LSAB+). Type and distribution of lymphatics in different lesions of the cervix were analyzed. We found significant correlation between lymphatic microvessel density and tumor grade and particular distribution of the lymphatics linked to histopathologic type of the lesions. Also, differences was found in lymphovascular invasion interpretation between routine Hematoxylin and Eosin staining specimens and immunohistochemical ones. Our results showed differences in the distribution and D2-40 expression in lymphatic vessels and tumor cells from the cervix lesions linked to histopathology and tumor grade.

The differences between the endothelial area marked with CD31 and CD105 in colorectal carcinomas by computer-assisted morphometrical analysis.

UNLABELLED: The aim of our study was to compare the CD31 and CD105 endothelial area (EA) by computer-assisted morphometrical analysis in colorectal carcinomas (CRC). Two hundred and eleven surgical specimens with CRC were immunohistochemical analyzed with markers for angiogenesis CD31 and CD105 (Endoglin). We determined the area of endothelial cells occupied in the microscope field (EA). RESULTS: The median area was 6.93 +/- 4.25% for CD31, respectively 5.65 +/- 2.23% for CD105. In the majority of cases, the CD31 EA was higher than CD105 EA. In the cases with the predominance of mature vessels, and also in the cases after radiotherapy, the CD105 EA was higher than CD31 (5.69 +/- 2.49%, respectively 10.23 +/- 5.93%). In our study, we tried to describe the clinico-morphological features of these cases. CONCLUSIONS: The CD105 seems to be the best marker for study of neoangiogenesis in CRC. Sometime, CD105 marks the activated endothelium of preexistent mature vessels. The radiotherapy destroys the neoformed but also the preexistent vessels. For the antiangiogenic treatment, it is important to determine the intensity of angiogenesis but also the type of neoformed vessels.

From conventional pathologic diagnosis to the molecular classification of breast carcinoma: are we ready for the change?

Breast cancer is the most frequent malignant tumor in women and the diagnosis, prognosis and therapeutic strategy are based on the pathologic report. In last years, it was shown that conventional pathologic diagnosis brings few data about prognosis and tells nothing about the response of the tumor to specific therapy. In an effort to improve the molecular characterization of breast cancer, gene profile analysis was performed in a large number of cases. Based on this analysis, there were characterized five molecularly different subclasses: basal-like, luminal type A and B, HER-2, and unclassified. It was shown that prognosis and response to adjuvant therapy is significantly different in these five subtypes. Immunohistochemistry was demonstrated to be a good and acceptable surrogate of the gene analysis. A panel of antibody that includes estrogen receptors (ER), progesterone receptors (PR), Her2 protein, cytokeratin 5 (CK5), epidermal growth factor receptor (EGFR), p53 mutation, and Bcl-2 expression, can discriminate between these five molecular subclasses. In the present review there are presented the main characteristics of the molecular subclasses, the relationships with the conventional pathologic classification, critical problems of the molecular classification and their impact on prognosis and therapy.

Analysis of the immunohistochemical expression of mammaglobin A in primary breast carcinoma and lymph node metastasis.

Mammaglobin A is a specific marker of the normal and neoplastic mammary tissue that usually is detected by RT-PCR. Few data are available about the immunohistochemical expression of this marker in mammary carcinoma and about the significance of the positive reaction. Our purpose was to investigate the sensitivity of the mammaglobin expression in breast cancer and to determine its correlations with conventional prognostic parameters. There were investigated 47 patients with breast carcinoma, and slides from paraffin blocks were stained with an antibody against mammaglobin. The immunohistochemical reaction was scored based on the percentage of positive tumor cells in both primary tumors and lymph node metastasis. Positive reaction for mammaglobin was found in the normal mammary tissue adjacent to the tumor in all cases, in 78.72% primary breast carcinoma, and in 58.06% of cases with lymph node metastases. A significant correlation was found between the mammaglobin expression in the primary tumor, grade, and lymph node status, but not with the age of the patient, pathologic subtype of carcinoma and stage of the tumor. The ductal in situ carcinoma associated to the invasive tumor did not influence significantly the prognostic value of mammaglobin expression. Out results suggest that mammaglobin is a sensitive marker of breast carcinoma, it defines a subgroup of patients with better prognosis and is a useful method to detect breast cancer metastases.

VEGF and VEGFRs expression in oral squamous cell carcinoma.

Oral cancer is an important cause of worldwide morbidity and mortality, with substantial economic, physiological, and psychosocial impacts due to its treatment modality and a great risk for recurrences and second primary oral squamous cell carcinomas (OSCC) development. Therefore, it is very important to understand the underlying cell biology of such tumors. It is now a well-accepted fact that angiogenesis is essential for the growth and metastasis of solid tumors, including head and neck squamous cell carcinoma. The main factor responsible for angiogenesis is VEGF and its receptors. It has been demonstrated that VEGFRs are also present on tumor cells themselves and other cells from the tumor microenvironment, in addition to tumoral endothelial cells (ECs). Therefore between these cells take place numerous and different interactions mediated via paracrine/autocrine pathways that promote angiogenesis, uncontrolled tumor proliferation and metastasation. In consequence, estimation of VEGF expression and its receptors became a reliable prognostic tool in OSCCS, predicting the poor disease-free survival, poor overall survival, and metastatic disease. Understanding the distribution and role of VEGF and its receptors in the progression of OSCC will be essential to the development and design of new therapeutic strategies.

Podoplanin expression in advanced-stage gastric carcinoma and prognostic value of lymphatic microvessel density.

In gastric cancer, lymph node metastasis is a major prognostic factor. Tumor lymphangiogenesis promotes metastasis in experimental models, but in human tumors data about the presence and clinical significance of lymphatic vessels in the tumor area are controversial. We investigated 70 patients with advanced-stage gastric carcinoma and the pathological examination showed 40 cases with intestinal subtype and 30 cases with diffuse subtype. Forty three from 70 cases had regional lymph node metastasis. Additional slides were stained with an antibody against podoplanin, and lymphatic microvessel density (LMVD) was evaluated in the tumoral and peritumoral areas. Lymphatic vessels were identified in tumor area in all cases and LMVD was higher in the peritumoral than in the tumor area. Podoplanin-positive vessels in tumor area were usually small, with narrow lumen. A significant correlation was found between LMVD and stage of the tumor (p<0.002) and lymph node metastasis (p<0.031), but not with the pathological subtype and grade of the tumor. We found tumor cells in the lumen of lymphatic vessels in 11 cases, whereas tumor cells expressing podoplanin were found in 4 cases of less differentiated diffuse subtype gastric carcinoma. In conclusion, our results suggest that LMVD predicts tumor stage and lymph node metastasis, and podoplanin-positive tumor cells select a subgroup of tumors with high potential of invasion and metastasis.

Neural granular cell tumor. A case report.

It is presented the case of an old female with a solitary tumor at the level of the thorax. The specimen was processed using the routine histological technique and slides were stained with conventional morphologic, histochemical and immunohistochemical methods. On Hematoxylin-Eosin stained slides were noticed large cells with acidophilic cytoplasm, with granular pattern. S100 protein was intensely expressed in all tumor cells and neuron specific enolase was moderate positive. CD68 positive reaction was considered the expression of lysosomes accumulation in the cytoplasm of tumor cells. Histological and immunohistochemical findings are consistent with the diagnosis of neural granular cell tumor.

E-cadherin expression in invasive breast cancer.

There were investigated 22 cases with invasive breast carcinoma from the archive material, and the immunohistochemical expression of E-cadherin was correlated with clinical stage, pathological type, grade of the tumor, and lymph nodes status. The expression of E-cadherin was assessed by the pattern of the final product of reaction and number of positive cells. The reaction was appreciated as normal if over 70% of tumor cells showed membrane of membrane and cytoplasmic pattern, and aberrant, if less than 70% of tumor cells were positive. There were found 45.5% cases with normal expression and 54.5% with aberrant expression. Strong positive reaction was found mainly in tumor cells invading the adipose tissue, but the reaction was weak or negative in tumor cells within the vessels. Both normal and aberrant expression of E-cadherin correlates with grade and with clinical stage. In our study was found that the increase of the tumor grade is associated with decrease in the expression of E-cadherin. Tumors over 2 cm in their larger diameter showed a decreased expression of E-cadherin. Seventeen from 22 cases with lymph node metastasis had positive reaction in the primary, but there were not found significant differences between the normal and aberrant expression.

Immunohistochemical evaluation of the tumor neoangiogenesis as a prognostic factor for gastric cancers.

INTRODUCTION: The angiogenesis, the process by which new blood vessels are formed, plays an essential role in the survival of the malignant cells, in the local expansion and tumor invasion, as well as in the appearance of distant metastases. MATERIAL AND METHODS: We evaluated the relation between MVD, the VEGF expression, the clinicopathologic factors and the survival in patients with gastric cancer. A prospective study has been carried out, regarding the evolution and aggressiveness of the gastric cancer, with a duration of 5 years, 61 patients that underwent a surgery for gastric cancer being included in the study. The immunohistochemical reactions for CD34 and VEGF were performed for all gastric cancers cases included in the study group. RESULTS: MVD has shown in the gastric carcinomas an average value significantly higher in comparison to the normal mucosa (38.7 vs. 12.5, p<0.001 ES). In the intestinal type we have noticed a much lower average MVD than the average MVD in the diffuse type of gastric carcinomas (36.8 vs. 41.6) (p=0.02478 S). The anaplastic carcinoma and the signet ring cell carcinoma are detaching themselves as histological forms associated to an intense neoangiogenesis activity. The neoangiogenesis activity is correlated with: the histologic grade, the lymphovascular invasion, the level of extend, the lymph node metastasizing, the distant metastasizing and the TNM stage. The positive immunoreactions for VEGF are significantly more frequent in the gastric carcinomas, in comparison to the normal gastric mucosa (65.6% vs. 6.5%, p<0.001 ES). The immunoreactions to the VEGF protein were positive in 71.1% of the intestinal carcinomas, significantly more frequent in comparison to the diffuse type carcinomas (52.9%) (p=0.018178 S). Our results show a tight correlation between the histologic grade, the level of the tumor invasion and the VEGF expression. CONCLUSIONS: Our results prove the major correlation between the VEGF expression and the 5-year survival rate of the patients with gastric cancer, the survival rate for the carcinomas with VEGF +~++ being significantly lower than for the VEGF negative ones (12.5% vs. 23.8%) (p=0.027983 S). Our study proves a tight correlation between the VEGF expression and the MVD (p=0.03986 S), these factors playing an important role in the tumoral biologic conduct, in the progression and the prognostic.