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Bladder neck invasion is an independent predictor of prostate-specific antigen recurrence.

BACKGROUND: The 1997 TNM staging system for prostatic carcinoma and the 2002 revision thereof classified prostatic carcinoma with bladder neck involvement classified as pT4 disease. This classification is based on the belief that tumors that invade surrounding structures are more aggressive and warrant higher staging than tumors that do not invade surrounding structures. Recent reports in the literature suggested that microscopic involvement of the bladder neck does not carry independent prognostic significance. Therefore, resection specimens with bladder neck involvement should not be classified as pT4. The current study prospectively examined the prognostic significance of bladder neck involvement by prostatic carcinoma. METHODS: The authors analyzed the totally embedded and whole-mounted radical prostatectomy specimens from 364 consecutive patients. The mean patient age was 66 years (range, 41-77 years). The bladder neck, which had been coned from the specimen, was cut in a perpendicular fashion. Involvement of the bladder neck was defined as the presence of neoplastic cells within the smooth muscle bundles of the coned bladder neck. The data were prospectively collected. Bladder neck involvement was analyzed in relation to age, preoperative prostate-specific antigen (PSA) level, prostate weight, Gleason score, final pathologic classification, tumor volume, surgical margin status, the presence of high-grade prostate intraepithelial neoplasm, multifocality, seminal vesicle invasion, extraprostatic extension, perineural invasion, and PSA recurrence. RESULTS: Bladder neck involvement was found in 22 (6%) of 364 patients. Univariate results indicated that bladder neck involvement versus no bladder neck involvement was significantly associated with preoperative PSA (P < 0.001), higher pathologic classification (P < 0.001), larger tumor volume (P < 0.001), extraprostatic extension (P < 0.001), positive surgical margins (P < 0.001), and PSA recurrence (P = 0.003). In a multivariate logistic regression model controlling for pathologic classification, Gleason score, and surgical margin status, bladder neck involvement was an independent predictor of PSA recurrence (P = 0.04). The adjusted odds ratio for bladder neck involvement was 3.3 (95% confidence interval, 1.04-10.03). CONCLUSIONS: In the current study, bladder neck involvement was an independent predictor of early PSA recurrence. The data demonstrated the importance of continued assessment of bladder neck invasion and supported the placement of tumors with bladder neck involvement in a stage that recognizes the prognostic implications of such involvement.

Adult↗

Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma.

BACKGROUND: Synovial sarcomas are high-grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER-2/neu. METHODS: Archival specimens of synovial sarcoma (n=38) representing 30 patients were assessed for EGFR and HER-2/neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real-time polymerase chain reaction (Q-PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in-situ hybridization. RESULTS: EGFR and HER-2/neu protein were detected by immunohistochemistry in 21 of 38 (55.3%) and 20 of 38 (52.6%) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER-2/neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2%). HER-2/neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0%) showed HER-2/neu immunoreactivity and 1 (17%) demonstrated EGFR expression. Q-PCR demonstrated the presence of mRNA for EGFR and HER-2/neu in 19 of 30 specimens (63.3%) and 22 of 30 specimens (73.3%), respectively. EGFR and HER-2/neu were expressed at low concentrations compared with the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed. CONCLUSIONS: EGFR and HER-2/neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients.

Adolescent↗

Fine-needle aspiration cytology of angiomatoid malignant fibrous histiocytoma.

Angiomatoid malignant fibrous histiocytoma (AMFH) is a rare, low-grade malignant mesenchymal neoplasm that affects mostly the extremities of children and young adults. Excisional surgery is the adequate treatment. The cytologic, immunocytologic, and histologic features noted in two patients having AMFH are presented. Cytologic smears showed histiocyte-like cells dispersed and in clusters, in close relation with eosinophilic mesenchymal fragments in a bloody background with lymphocytes. The tumor cells showed mild to moderate anisocariosis, often with nucleolus and vast, fragile cytoplasm. A fibroblastic-like spindle to ovoid cell population was also present in one patient. Immunohistochemical results are most consistent with myofibroblastic cell differentiation. When accompanied by adequate clinical information and ancillary techniques, a specific preoperative cytologic diagnosis is possible.

Adolescent↗

Canine prostatic intraepithelial neoplasia: is the comparative model relevant?

BACKGROUND: Histologic sections from an archival collection of a veterinary teaching hospital were examined to determine the likelihood of detection of canine high-grade prostatic intraepithelial neoplasms (HGPIN), as a prelude to use of the canine model of prostatic carcinogenesis for chemopreventive strategies. METHODS: Tissue specimens representing clinically healthy (normal) prostate glands, benign prostatic hyperplasia, and prostatic carcinoma were examined in one tissue plane for histological evidence of HGPIN. RESULTS: No histological evidence of HGPIN was detected in 20 normal prostate glands or 95 prostate glands with benign prostatic hyperplasia. Seven of 20 prostatic carcinomas had synchronous HGPIN. CONCLUSIONS: Histological evidence of HGPIN is unlikely to be detected in the healthy or hyperplastic canine prostate gland with the clinically-procured biopsy. This might diminish the usefulness of canine HGPIN in temporal studies of chemoprevention of prostate cancer. HGPIN was found simultaneously with prostatic carcinoma in more than one-third of the carcinomas examined.

Animals↗

[Retiform hemangioendothelioma. Clinico-pathologic case report and discussion of the group of low malignancy vascular tumors].

We report a locally recurrent retiform haemangioendothelioma (RHE) on the right great toe in a 40-year-old woman. There was a secondary soft tissue lesion on her right lower leg. Histologically, primary lesion, local recurrence and the secondary soft tissue lesion (soft tissue metastasis?) showed identical features. Long, arborizing, neoplastic blood vessels were lined by CD31 and factor VIII-positive, monomorphic endothelial tumour cells; focally solid tumour areas, papillae and a prominent inflammatory infiltrate consisting of mature B and T lymphocytes were noted. The concept and the group of low-grade malignant vascular neoplasms is discussed, with special emphasis on inclusion of RHE in this category.

Adult↗

Mucinous tubular and spindle cell carcinoma: a report of 15 cases and a review of the literature.

Mucinous tubular and spindle cell carcinomas are low-grade renal epithelial neoplasms, which were first recognized as a specific entity in the World Health Organization 2004 classification. Forty-five documented cases have been reported. We present 15 additional cases that were incidentally discovered in ten women and five men, with a mean age of 53 years. The tumor is characteristically made up of large eosinophilic regular spindle cells separated by a myxoid stroma with intercellular alcian-blue-positive clear droplets. In peripheral areas, elongated tubules and papillae covered by cubic cells are found. Until this entity had been defined, pathologists used to classify these tumors as variants of solid papillary carcinomas with compressed and elongated papillae, metanephric adenomas, and sarcomatoid carcinomas. In the literature, cytogenetic data indicate various chromosomal losses and gains, but no loss of 3p or trisomy 7 and/or trisomy 17. In two cases, we demonstrate chromosomal loss involving chromosomes 1, 4, 6, 11, 8, 13, 14, 15, 18, and 22. In our 15 cases, immunohistochemistry favored a distal tubule origin (EMA(+), AE1/AE3(+), CK7(+), CK19(+), E-cadherin(+), AMACR(+), and CD10(-)). Prognosis was favorable in our cases, while in the literature, two metastatic cases were reported. Further investigations are required to determine the frequency and true prognosis of these tumors, which are easily identifiable morphologically.

Adult↗

Digital Immunophenotyping of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Subtypes With Specific Tumor-Immune Microenvironment Features.

Atypical carcinoids (ACs) and large cell neuroendocrine carcinomas (LCNECs) are defined by the WHO as intermediate- and high-grade lung neuroendocrine neoplasms, respectively, based on morphological criteria; however, treatment strategies remain debated. Given the emerging role of the tumor microenvironment (TME) and tumor-infiltrating lymphocytes (TILs) in cancer prognosis and therapy response, this study aimed to characterize the immune landscape of ACs and LCNECs comprehensively. Immunohistochemistry for T-cell markers (CD3, CD8), immune checkpoints (PD-1, PD-L1), HLA molecules (HLA-DR, HLA-I), and fibroblasts (&#x3b1;-SMA) was performed on a re-evaluated cohort of 56 ACs and 104 LCNECs. Digital image analysis quantified intra-tumor (iTILs) and stromal (sTILs) CD3 and CD8 TILs in the whole slide and in specific tumor regions (invasive margin [IM] and central tumor [CT]). LCNECs exhibited significantly higher stromal T-cell infiltration, immune checkpoint expression, and HLA compared to ACs (p&#x2009;<&#x2009;0.001), while &#x3b1;-SMA was more prominent in ACs. No ACs showed PD-L1 tumor expression. Digital quantification confirmed greater iTILs and sTILs in LCNECs across all regions, with moderate concordance to manual counts. Interestingly, TIL parameters were higher at the IM than in the CT (p&#x2009;<&#x2009;0.001). Using Boruta feature selection algorithm, Principal Component Analysis and Hierarchical Clustering, three patient clusters were identified: Cluster 1 (mainly ACs, low TILs, favorable prognosis), Cluster 2 (mixed histology, intermediate TILs, moderate prognosis), and Cluster 3 (mostly LCNECs, high TILs, poor prognosis), with distinct TME marker profiles. PD-L1 tumor expression was strongly linked to Cluster 3. These findings suggest that ACs and LCNECs may be stratified into three distinct immune clusters, highlighting the heterogeneity of their tumor microenvironment and providing a rationale for further translational studies.

Humans↗

Immunophenotypic differences between normal glia, astrocytomas and malignant gliomas: correlations with karyotype, natural history and survival.

The karyotypic and antigenic phenotypes of early passage normal and malignant glial cultures were correlated in vitro. Astrocytomas (4) were distinguished from the normal glia (8) by a mixed near-diploid karyotype and anchorage-independent growth. Malignant gliomas (41) demonstrated cytogenetic abnormalities ranging from mixed normal G- and Q-banded and near-diploid cultures, through mixed near-diploid/hyperdiploid to predominantly hyperdiploid stem-lines. This correlated with the differential expression of certain antigens and established qualitative antigenic differences from normal glia. Associations were found between histopathologic grade of glial neoplasm and the expression of antigens 5.1H11 (p = 0.0002), CNT/11 (p = 0.001), CNT/10 (p = 0.004), CAT301 (p = 0.014), M111 (p = 0.024), and L101 (p = 0.044). An ominous association was demonstrated between the duration of clinical survival and the expression of antigens 5.1H11 (p = 0.0007), CNT/10 (p = 0.027) and B2.6 (p = 0.038). Correcting for diagnosis and age, multivariate analysis demonstrated that HLA-DR (p = 0.050) and 5.1H11 (p = 0.069) were unfavorably correlated with patient survival. This suggests the application of the in vitro immunophenotype for its predictive utility, as well as a novel method of selection of tumor-associated antigens for monoclonal antibody-mediated immunotherapy.

Adolescent↗

Expression of pituitary adenylate cyclase activating polypeptide (PACAP) receptors in human glial cell tumors.

Twenty-three human gliomas were analyzed: 13 astroglial neoplasms including three grade II, four grade III, and six grade IV tumors; seven ependymomas; and three oligodendrogliomas. A crude membrane fraction was prepared within 30 min after surgical removal of the tumors and was immediately tested for the presence of pituitary adenylate cyclase activating polypeptide (PACAP) receptors. PACAP stimulated adenylate cyclase activity in 23 tumors, but a specific binding of [125I-acetyl-His1]PACAP-27 was detected in only 16 tumors. In all cases, PACAP-27 and -38 were equipotent (Kd or Kact of 1-3 nM) and were 100- to 1000-fold more potent than VIP. PACAP stimulated threefold the adenylate cyclase activity in the presence of GTP. The results were compatible with an interaction of PACAP with a highly selective type I PACAP receptor and not with a high-affinity VIP/PACAP type II receptor. The presence of PACAP receptors on glial neoplasic opens the possibility of a control of the tumor growth by this family of peptides.

Adenylyl Cyclases↗

Prognostic role of the histologic subtypes of renal cell carcinoma after slide revision.

OBJECTIVES: To evaluate concordance, using the kappa statistic, between tumour histotypes assigned at initial diagnosis and those after slide revision, and to assess the independent predictive value of reviewed tumour histotype. MATERIALS AND METHODS: We analysed records of 491 patients who had undergone partial or radical nephrectomy for renal cell carcinoma (RCC) in our department from 1986 to 2000. Pathologic slides were reviewed by one uropathologist blinded to original diagnoses and follow-up data, who reassigned histologic subtype and nuclear grades. RESULTS: Concordance between original and reviewed histotypes was substantial (kappa = 0.52). Data were affected by the year of initial diagnosis: Concordance was moderate (kappa = 0.43) in patients treated from 1986 to 1997 and substantial (kappa = 0.73) in those observed thereafter. The original histotype did not stratify the cancer-related outcome. According to the reviewed histotypes, the 5-year cancer-specific survival probabilities of conventional, papillary and chromophobe RCC patients were 81.3%, 90.1% and 100%, respectively (p = 0.009). Patients with conventional RCC showed significantly lower cancer-specific survival than those with papillary or chromophobe RCC, even in the cases with locally advanced (p = 0.04) or high-grade (p = 0.02) neoplasms. The reviewed histologic subtype was not an independent prediction of cancer-specific survival on multivariate analysis. CONCLUSION: Concordance between histologic subtype assigned before 1997 and after slide revision was only moderate. In univariate analysis, reviewed tumour histotype stratified cancer-related outcome, but the data of multivariate analysis were strongly influenced by the prevalent number of conventional RCC.

Carcinoma, Renal Cell↗

Postatrophic hyperplasia of the prostate gland: neoplastic precursor or innocent bystander?

Postatrophic hyperplasia (PAH) of the prostate gland often demonstrates overlapping histological features with prostatic adenocarcinoma (PCA). These features include small acinar growth and enlarged nuclei with prominent nucleoli. Recent work has demonstrated that PAH is a proliferative, noninvoluting lesion. PAH is also histologically distinct from simple atrophy (SA), which has intermediate- to large-sized glands, minimal cytoplasm, and inconspicuous nuclei. However, despite overlapping features between PAH and PCA, high-grade prostatic intraepithelial neoplasm (HGPIN) is still considered the only direct neoplastic precursor to PCA. HGPIN resembles PCA in its topographic distribution, cytological appearance, and molecular alterations including chromosome 8p loss and chromosome 8 centromeric gain. To examine the hypothesis that PAH is the earliest histologically distinct precursor to HGPIN or PCA, the frequency, distribution, proliferative state, and chromosome 8 gain of benign prostate, SA, PAH, HGPIN, and PCA were analyzed. Forty radical prostatectomy specimens from men with clinically localized PCA were systematically analyzed. Proliferation was determined by Ki-67 immunohistochemistry (MIB-1) on formalin-fixed, paraffin-embedded tissue and quantified by digital image analysis from a total of 5,510 sample areas with benign, SA, PAH, HGPIN, and PCA. A tissue microarray was constructed to evaluate 8c gain using interphase fluorescence in situ hybridization. SA foci (n = 129) and PAH foci (n = 114) were identified in the 40 cases of which 74% (95 of 129) and 88% (100 of 114) were seen in the peripheral zone, respectively (P = 0.006). PAH and SA were identified adjacent to PCA in 28% (32 of 114) and 14% (18 of 129) of foci examined, respectively (P = 0.007). The median number of proliferating nuclei increased significantly from benign (1.20%), SA (2.67%), PAH (3.62%), HGPIN (6.14%), to PCA (12.00%) (P < 0.001). The median percentage of nuclei with more than three centromeric probe signals (chromosome 8c gain) for SA, HGPIN, PAH, and PCA were 2.1, 2.8, 4.0, and 6.0%, respectively, as compared to benign prostate with 1.3% (P = 0.006). In conclusion, the present study identified a strong topographic association between PAH and PCA. PAH is also seen often to be closely associated with chronic inflammation. Proliferation of PAH is significantly greater than benign prostatic epithelium and SA but less than HGPIN or PCA. Gain of 8c is significantly greater in PAH than benign prostate, SA, and even HGPIN. These findings demonstrate a strong association between PAH and PCA, supporting its role as a neoplastic precursor.

Adenocarcinoma↗

E cadherin expression in normal and neoplastic canine mammary gland.

The epithelial intercellular adhesion molecule, E cadherin, was evaluated immunohistochemically in a series of normal and malignant neoplastic canine mammary glands. The normal glands showed strong immunolabelling at the intercellular borders of all the ductal cells. Tubular and papillary mammary adenocarcinomas had reduced intercellular E cadherin positivity with "heterogeneous" or "cytoplasmic" distribution. Solid and squamous cell carcinomas were negative. These results suggest that reduced expression and abnormal distribution of E cadherin may be related to the differentiation grade of these neoplasms.

Animals↗

A centralized comparison of radical perineal and retropubic prostatectomy specimens: is there a difference according to the surgical approach?

PURPOSE: We performed a central review of pathology specimens from radical perineal and radical retropubic prostatectomies performed by a single surgeon. We determined whether differences exist in the 2 approaches in regard to the ability to obtain adequate surgical margins around the tumor and adequate extracapsular tissue around the prostate, and avoid inadvertent capsular incision. MATERIALS AND METHODS: The review included whole mount prostates from 60 patients who underwent radical retropubic prostatectomy and 40 who underwent radical perineal prostatectomy. The pathologist (N. S. G.) was blinded to the surgical approach. All prostatectomies were consecutive and performed by the same surgeon (H. J. K.). To ensure consistency of the pathological measurements patients were excluded from analysis if they had undergone preoperative androgen ablation or a nerve sparing procedure, leaving 45 retropubic and 27 perineal prostatectomy specimens for further evaluation. Pertinent clinical parameters were assessed and a detailed pathological analysis of each specimen was performed. RESULTS: In the retropubic and perineal groups 78% of the tumors were organ confined (stage pT2) with extracapsular extension (stage pT3) in the majority of the remaining patients. There was no significant difference in the positive margin rate for the retropubic and perineal procedures (16% and 22%, p = 0.53) or for Gleason 6 and 7 tumors only in the 2 groups (10% and 17%, respectively, p = 0.47). The capsular incision rate was 4% in each group. The distance of the tumor from the posterolateral margins and the amount of extracapsular tissue excised were equivalent in each group. Subgroups of patients with a prostate of less than 50 gm. and containing only low grade, low stage neoplasms were also analyzed. Subgroup analysis showed no difference in any variable. CONCLUSIONS: Radical perineal prostatectomy is comparable to radical retropubic prostatectomy for obtaining adequate surgical margins, avoiding inadvertent capsular incisions and excising adequate extracapsular tissue around tumor foci. Additional patient accrual and prostate specific antigen followup would further help validate the similar efficacy of the 2 surgical approaches as treatment for prostate cancer.

Adult↗

Ureteroscopic biopsy: technique and specimen preparation.

Because tissue samples obtained ureteroscopically are small, the techniques for biopsy and for handling and processing the samples are crucial. Our aim is to describe the biopsy technique in great detail so other centers can reproduce it. Patients were evaluated by retrograde ureteropyelography and ureteroscopy for diagnosis. The entire collecting system was examined using a combination of small-diameter rigid and flexible ureteroscopes. Samples were retrieved by aspiration, saline lavage, or, when possible, biopsy of visible tumor by a basket or cup forceps. Multiple samples were obtained from all patients. Fresh specimens were hand delivered to the cytopathology laboratory, where they were evaluated with the cytospin technique. A cell block was prepared whenever there was any visible tissue in the sample. Since we have practiced this technique of handling specimens, our ability to diagnose and grade upper tract neoplasms ureteroscopically has improved markedly. Use of this technique can improve the diagnostic accuracy of ureteroscopic biopsy.

Biopsy, Needle↗

Pathologic characteristics of prostatic adenocarcinomas: a mapping analysis of Korean patients.

Pathologic characteristics of the prostatic adenocarcinoma in Koreans are not clear. We studied 132 cases of prostatectomy specimens using mapping analysis to discover the pathologic characteristics of the Korean prostatic adenocarcinoma. Mean values were as follows: serum prostate-specific antigen level (sPSA), 16.4 ng/ml; tumor volume, 27.5%; size, 2.4 cm; Gleason score, 7.7; and p53 expression, 9.8%. Rates of multifocal tumors and high-grade prostatic intraepithelial neoplasm (HPIN) were 33.3 and 65.2%. The Gleason score, tumor volume%, tumor size and sPSA were correlated with each other. Korean prostatic adenocarcinomas showed higher Gleason scores, lower rates of HPIN and multifocality, and lower p53 expression in comparison to Western prostatic adenocarcinomas. These data may be a basis for pathologic characteristics of Korean prostatic adenocarcinoma that has now been increasing.

Adenocarcinoma↗

Myxoid plexiform fibrohistiocytic tumour.

Plexiform fibrohistiocytic tumour is a low-grade malignant mesenchymal neoplasm of myofibroblastic origin with the capacity for biphasic differentiation toward a fibroblastic or histiocyte-like morphology. We report a case of this rare tumour presenting as a tender subcutaneous nodule on the scalp of a 58-year-old man. Histopathological examination revealed multinodular biphasic proliferation of fibroblast-like and histiocyte-like cells with a few osteoclast-like giant cells. This case is notable for the rare myxoid changes, which may reflect a different behaviour of this tumour when occurring in older people.

Diagnosis, Differential↗

Recurrent polymorphous sweat gland carcinoma of the skin.

Polymorphous sweat gland carcinoma is an unusual, recently described variant of low-grade malignant adnexal neoplasm of the skin characterized by a prolonged clinical course and predilection for the extremities. We describe a case of recurrent polymorphous sweat gland carcinoma in a 56-year-old man who presented with multiple large skin nodules distributed along the flexor surface of his left arm. The lesions were treated by surgical excision; multiple local recurrences, as well as the development of new lesions, were observed over a period of 5 years. No distant metastases have been observed so far. The clinical differential diagnosis and management of these unusual lesions are discussed.

Arm↗

Morphologic changes and altered gene expression in an epithelioid hemangioendothelioma during a ten-year course of disease.

Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular neoplasm with unpredictable prognosis. We report on a patient suffering from a vascular neoplasm with primary manifestation in the skeleton and subsequent development of lesions of EHE in the spleen, liver and lung. Based on the assumption that involvement of visceral organs was due to metastatic spread, changes in clinical behavior, morphology, and proliferation index suggest malignant progression of the tumor. Analyzing the expression of genes known to be involved in the pathogenesis of vascular tumors, we found that the appearance of less differentiated tumor was paralleled by an accumulation of TP53 and murine double minute-2 (MDM-2) protein, decreased caveolin-1 (CAV-1) expression, and increased vascular endothelial growth factor (VEGF) expression. Mutations of the von-Hippel-Lindau-tumor-suppressor-gene (VHL) were excluded as mechanism of VEGF upregulation. Therefore, we propose that the expression of TP53, MDM-2, CAV-1 and VEGF as a marker of biologic behavior be verified in a larger case study of EHE.

Arabidopsis Proteins↗