Grade Of Anaplasia Research Articles

Relationship between Glutathione-Dependent Enzymes and the Immunohistochemical Profile of Glial Neoplasms.

This research aimed to investigate the relationships between the parameters of glutathione metabolism and the immunohistochemical characteristics of glial tumors. Postoperative material from 20 patients with gliomas of different grades of anaplasia was analyzed. Bioinformatic analysis of the interactions between the gliomas’ immunohistochemical markers and their glutathione-dependent enzymes was carried out using the STRING, BioGrid, while Signor databases revealed interactions between such glioma markers as IDH and p53 and the glutathione exchange enzymes (glutathione peroxidase, glutathione reductase, glutathione S-transferase). The most pronounced relationship with glutathione metabolism was demonstrated by the level of the nuclear protein Ki67 as a marker of proliferative activity, and the presence of the IDH1 mutation as one of the key genetic events of gliomagenesis. The glutathione system is an active participant in the body’s antioxidant defense, involving the p53 markers and MGMT promoter methylation. It allows characterization of the gliomal cells’ status at different stages of tumor development.

Intracranial meningiomas: clinical, intrascopic and pathomorphological causes of recurrence (literature review)

Introduction. Meningiomas are the second most common central nervous system (CNS) tumors in adults. most meningiomas are benign tumors. Anaplastic and atypical meningiomas account for 25% and have a high recurrence rate even after radical tumor resection and radiotherapy. The prognosis of patients with anaplastic meningiomas remains disappointing; most of them die within the first 2 to 5 years after surgery. Purpose: to discuss the challenges in diagnosis and treatment of recurrent meningiomas, to identify the causes of tumor progression, and to assess the clinical features and radiographic findings as well as specific pathomorphological and molecular genetic characteristics. material and methods. We searched for publications in the Pubmed, EMBASE, Cohrane Library and eLibrary databases published between January 2000 and January 2019 on the issue of recurrent intracranial meningiomas, in particular atypical and anaplastic meningiomas. Results. The review systematizes data on the prognostic factors for survival, relapse-free period, and disease progression. particular attention was paid to the radical resection of the tumor and the assessment of the grade of anaplasia. The current data on radiotherapy and drug therapy were presented. the controversial issues of approaches to the assessment of morphological prognostic criteria were discussed. The current knowledge on the most common genetic mutations in meningiomas, the prospects for their study and use for targeted therapy were presented. Conclusion. The management of meningioma still presents some unresolved issues. There are no optimal standards for diagnosis and treatment of patients with meningiomas that would take into account biological characteristics, including growth characteristics and molecular genetic profile. There are no clear prognostic criteria for recurrence and continuity in further management after surgical treatment, which affects the mortality rate and quality of life in this category of patients. New fundamental data that will determine a different strategy in the treatment of intracranial meningiomas are needed.

Intratumor morphologic and molecular genetic heterogeneity in astrocytomas of different grade of malignancy in the material from the first operation

Introduction. Intratumor heterogeneity is one of the key reasons for unfavourable prognosis in malignant tumors. Astrocytic tumors are known to develop therapy resistance inevitably during the course of disease. One of possible reason is tumor heterogeneity. Purpose. The aim of this work was to assess the intratumor morphologic and molecular heterogeneity in diffuse astrocytoma, anaplastic astrocytomas and primary glioblastomas. Material and methods. We conducted morphologic (n=22) and molecular-genetic (n=8) analysis of surgical specimens obtained from primarily operated glioblastoma giv (gb), anaplastic astrocytomas giii (aa) and diffuse astrocytoma gii (da) patients aged 18 years and older in whom total or subtotal tumor resection was performed. Tissue sampling for the analysis was performed from 5 equidistant areas of each tumor. Morphologic diagnosis was established according to who classification of central nervous system tumors (2007/2016). Mgmt, c-kit, top2a, pdgfr-α, ercc1, vegf genes mrnaexpression was assessed by rt-pcr. Idh1 and idh2 mutational status was evaluated by allele-specific pcr. Results. Morphologic heterogeneity was evident in 72,7 % tumors (16/22) overall. Heterogeneity was observed in 68,8 % (11/16) of gb, 80 % (4/5) of aa and in the only case of da. In 50 % of cases at least 3 different morphologic variants were seen in different areas of the tumor. This morphologic heterogeneity presented as the combination of different grades of anaplasia (gii – giv) in one tumor. Molecular profile was assessed in 48 expression analysis of genes: mgmt, c-kit, top2a, pdgfr-α, ercc1, vegf from 8 patients. Intratumoral molecular heterogeneity was revealed in 41,7 % of cases (20/48). Conclusion. The presence of intratumoral heterogeneity should be taken into account during surgery for adequate tumor sampling for histologic and molecular analysis which is critical for proper assessment of prognosis and following treatment planning.

High risk histopathological factors in retinoblastoma in upfront enucleated eyes: An experience from a tertiary care centre of Pakistan.

Background & Objectives:The assessment of histopathological risk factors (HRFs) in retinoblastoma in upfront enucleated eyes is important in deciding treatment protocols. Limited data is available from the developing countries as very few studies were conducted on retinoblastoma. The study aims to report this data from Pakistan.Methods:This cross-sectional study included treatment naïve retinoblastoma patients who underwent upfront enucleation between 2017 to 2021. Various tumor characteristics i.e. laterality, size, histologic grade, anaplasia grade, growth pattern, extent and length of optic nerve invasion, pathologic staging, tumor involvement of ocular structures were assessed. High-risk factors such as involvement of anterior chamber, choroidal, scleral, extrascleral, and optic nerve were also noted.Results:A total number of 54 patients were enrolled, out of which 53.7% were females while remaining were males. Median age at presentation was 24 months. Unilateral tumor was seen in 92.6% cases. Most frequent histologic grade was G2 (64.7%) and moderate anaplasia was observed in 59.2% cases. Vitreous involvement was seen in (86.5%). Pathologic staging of most of the tumors was pT1 (39.2%). Assessment of high-risk factors revealed that optic nerve involvement (35.1%) was the most common finding with retrolaminar tumor invasion seen in 75% cases. Choroidal invasion (≤3mm) was seen in 55.6% of patients. Limited involvement of anterior chamber (3.8%), sclera (7.4%), and extrascleral (3.8%) tissue was also observed.Conclusion:The presence of high risk histopathological factors in enucleated eyes diagnosed with retinoblastoma are known to have a profound impact on the risk stratification as well as decision of future treatment plan.

MP61-03 A NEW METHOD FOR ASSESSING THE DEGREE OF CELLULAR ANAPLASIA IN KIDNEY CANCER BASED ON MORPHOMETRIC ANALYSIS OF 3D COMPUTER ASSISTED TOMOGRAPHY IMAGES

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance III (MP61)1 Sep 2021MP61-03 A NEW METHOD FOR ASSESSING THE DEGREE OF CELLULAR ANAPLASIA IN KIDNEY CANCER BASED ON MORPHOMETRIC ANALYSIS OF 3D COMPUTER ASSISTED TOMOGRAPHY IMAGES Anastasia Shpikina, Alexandra Proskura, Dmitry Fiev, Evgeniy Sirota, Vasiliy Kozlov, Mikhail Chernenkiy, Kirill Puzakov, Alexander Tarasov, Camilla Azilgareeva, Andrey Vinarov, and Petr Glybochko Anastasia ShpikinaAnastasia Shpikina More articles by this author , Alexandra ProskuraAlexandra Proskura More articles by this author , Dmitry FievDmitry Fiev More articles by this author , Evgeniy SirotaEvgeniy Sirota More articles by this author , Vasiliy KozlovVasiliy Kozlov More articles by this author , Mikhail ChernenkiyMikhail Chernenkiy More articles by this author , Kirill PuzakovKirill Puzakov More articles by this author , Alexander TarasovAlexander Tarasov More articles by this author , Camilla AzilgareevaCamilla Azilgareeva More articles by this author , Andrey VinarovAndrey Vinarov More articles by this author , and Petr GlybochkoPetr Glybochko More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002101.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We present the results of our retrospective analysis of the association between clinical variables and morphometric characteristics of kidney cancer with the grade of its histological structure differentiation. METHODS: The cellular anaplasia grade (G) of malignant tumors was determined in 231 cases: G1 - 77 cases (33.3%), G2 - 129 cases (55.8%), G3 - 24 cases (10.4%), G4 - in one case (0.4%). The study inclusion criteria were unilateral solid kidney neoplasms, age over 18 years. Exclusion criteria: bilateral and solitary kidney tumors, renal sinus, polyfocal and cystic kidney tumors. All patients underwent 3D modeling of the kidney tumor based on the contrast-enhanced CT of the kidneys. The clinical variables were age, gender, maximum neoplasm size. The morphometric parameters were the side of the tumor, tumor location on the kidney segments and surfaces, the tumor invasion depth, the shape of the renal parenchyma neoplasms. To assess the significance of kidney cancer predictors, we used multivariate and univariate logistic regression analysis. RESULTS: To assess the role of clinical variables and morphometric predictors in the G grade identification, all patients (n=231) were classified into two groups: group 1 (n=77) with G1; group 2 (n=154) with G2-G4. The multivariate analysis revealed a significant association between the G grade of renal tumors and the predominantly intraorgan tumor growth (p = 0.037). A high grade of tumor differentiation (G1) was associated with oval (p = 0.036) and spherical with a conical base (p = 0.018) renal neoplasms. The univariate analysis revealed a significant correlation between G and a spherical with a cone-shaped base kidney tumor only (p = 0.029). No statistically significant predictors were identified in the stepwise algorithm (p> 0.05). CONCLUSIONS: High kidney tumor grade (G3) in the multivariate analysis was associated with the predominantly interorgan tumor growth. While low kidney tumor grade (G1) was associated with oval and spherical with a conical base renal neoplasm and exophytic growth. The univariate analysis revealed correlation of G1 only with a spherical with a conical base renal tumor. The proposed algorithm can serve as an effective non-invasive tool for predicting kidney cancer G, the diagnostic value of which will improve with subsequent data collection and analysis. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1083-e1084 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anastasia Shpikina More articles by this author Alexandra Proskura More articles by this author Dmitry Fiev More articles by this author Evgeniy Sirota More articles by this author Vasiliy Kozlov More articles by this author Mikhail Chernenkiy More articles by this author Kirill Puzakov More articles by this author Alexander Tarasov More articles by this author Camilla Azilgareeva More articles by this author Andrey Vinarov More articles by this author Petr Glybochko More articles by this author Expand All Advertisement Loading ...

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy.

PurposeTo investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).Cases and MethodsNinety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG).ResultsAfter CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors.ConclusionsCHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB.

Prognostic relevance of DNA damage and repair biomarkers in elderly patients with hormone-receptor-positive breast cancer treated with neoadjuvant hormone therapy: evidence from the real-world setting.

Background:The logic behind the outcome of endocrine therapy in breast cancer has long remained poorly understood. The prognostic role of DNA damage and repair biomarkers (DDR) was explored in postmenopausal, hormone-receptor-positive breast cancer patients treated with neoadjuvant hormone therapy (NAHT).Methods:Data on 55 patients were included. The phosphorylated ataxia-teleangectasia and Rad3-related protein (pATR), phosphorylated ataxia-telangiectasia mutated (ATM) kinase, and phosphorylated H2A Histone Family Member X (γ-H2AX) were evaluated by immunohistochemistry in paired tissues collected at baseline and following NAHT. Biomarkers were considered both singularly and within signatures. Ki-67 percentage change was the primary biomarker endpoint. Classical endpoints were also considered.Results:The most favorable Ki-67 outcome was associated with the γ-H2AX/pATM signature (p = 0.011). In models of Ki-67 reduction, ‘luminal B’ subtype, higher grade of anaplasia, and the γ-H2AX/pATM signature tested as significant (p < 0.05 for all). Results were confirmed in multivariate analysis. No association was observed with pathologic response. An increase of ∆γ-H2AX in paired breast tissues was associated with longer event-free survival (p = 0.027) and overall survival (p = 0.042). In Cox models, both survival outcomes were solely affected by grade of anaplasia, with less favorable prognosis in the highest grades (p < 0.05 for both).Conclusions:We report novel evidence of the prognostic role of DDR biomarkers on important patient outcomes in postmenopausal hormone-receptor-positive breast cancer patients treated with NAHT. If confirmed in future and adequately sized trials, our results may help inform therapeutic decisions and clarify underlying biological mechanisms.

Immunohistochemical characteristics of bladder cancer in patients with virus-positive tumors

Background. Viral infection is a major factor in virus-associated carcinogenesis.Objective: to evaluate the expression of growth factors and markers of apoptosis, proliferative activity, and angiogenesis in patients with viral DNA-positive bladder cancer.Materials and methods. The study included 100 bladder cancer patients (72 males and 28 females) aged between 38 and 90 years (mean age 65 ± 10). Tumor tissue samples were tested by polymerase chain reaction to detect DNA of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2 respectively), high-risk human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein—Barr virus (EBV). Immunohistochemical analysis was performed in 32 patients and included the following markers: proliferation marker Ki-67, p63, apoptosis regulator Bcl-2, p53, angiogenesis marker CD31, adhesion protein CD44, and epidermal growth factor receptor (EGFR).Results. Viral DNA in tumor tissue was detected in 34 patients; of them, 50 % had poorly-differentiated tumors. Twenty-seven patients were found to have EBV DNA in their tumor tissue; 6 patients had CMV DNA; 5 patients had high-risk HPV DNA (types 16, 39, 45, 52, and 59); 1 patient had HSV1 and HSV2 DNA. Four out of 34 participants had mixed infections (1 case of HPV 59 + EBV; 2 cases of EBV + CMV; 1 case of CMV + EBV + HPV 31 and 52). We observed a strong correlation between the presence of EBV DNA and levels of CD31 and Ki-67 expression as well as between high-risk HPV DNA and Bcl-2 expression. High levels of antibodies against EBV capsid antigen were associated with EGFR and Ki-67 expression, whereas the level of antibodies against EBV nuclear antigen correlated with CD44 expression. We evaluated specific characteristics of expression of the markers analyzed depending on the tumor stage, grade of anaplasia, and recurrence. We also assessed morphological characteristics of changes in lymphocytic and plasma cell infiltrates.Conclusion. We found a correlation between the presence of viral DNA in bladder cancer tissue and markers of proliferative activity, angiogenesis, and apoptosis. Viral infection is likely to increase proliferative activity and suppression of apoptosis, which may cause tumor progression. Further studies are needed to assess this correlation.

336P - Case report of the effective use of BRAF inhibitor vemurafenib in a patient with relapse of pleomorphic xanthoastrocytoma

Pleomorphic xanthoastrocytoma is a rare tumor of the brain. It is approximately 1% of the astocytomas of the brain. In some cases, the tumor is well-demarcated and slow-growing with a favorable prognosis. At the same time reported cases of its malignant transformation with a poor prognosis. Most often this tumor occurs in a young age and manifest with epileptic syndrome. The main treatment is surgical. According to the literature, 30-40% of patients with pleomorphic xanthoastrocytoma detected mutation of V600E BRAF was. The patient 25 years old in January 2011 revealed a tumor of the left occipital lobe of the brain. 22 Jan 2011 completed the removal of a brain tumor. Morphologically diagnosed as a pleomorphic xanthoastrocytoma with signs of anaplasia grade 3, Ki-67 – 15%. In the postoperative, in February-April 2012, conducted a course of radiation therapy to the left occipital lobe of the brain with total focal dose 60 Gy. In September 2014 after 2 years and 8 months after the operation revealed a relapse of a brain tumor. 25 Sep 2014 made the removal of the recurrence of a brain tumor. Morphologically diagnosed as a pleomorphic xanthoastrocytoma with signs of anaplasia grade 4, Ki-67 > 20%. Carried out a genetic examination of the tumor. Revealed no methylation of the MGMT gene in the tumor. The identified mutation V600E BRAF in the tumor. In December 2014 marked the progression of the disease. Revealed continued tumor growth in the brain. The size of the recurrent tumor 4 x 3 cm. From December 2014 we started the targeted therapy with Vemurafenib. Achieved partial regression of the tumor in the brain. The size of residual tumors currently, less than 1 cm. Therapy with Vemurafenib lasts 1 year and 6 months. Thus, the presence of the V600E BRAF mutation is another target for effective treatment of recurrences of pleomorphic xanthoastrocytoma. Further studies are needed for the study of BRAF inhibitors in patients with pleomorphic xanthoastrocytoma.

Histopathologic Grading of Anaplasia in Retinoblastoma

To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Retrospective clinicopathologic study. The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Increasing grade of anaplasia was associated with decreased overall survival (P= .003) and increased risk of metastasis (P= .0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (P < .0001), choroidal invasion (P < .0001), and anterior segment invasion (P= .04). Multivariate analysis considering high-risk histopathology and anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (P= .01 for metastasis, P= .03 for death) but anaplasia was not (P= .63 for metastasis, P= .30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (P= .0004) and death (P= .01). Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy.

The study of antibodies level to glial tumours antigens in blood of neurooncological patients

The level of antibodies to tumor tissue at patients with brain tumors was studied using enzyme-linked immunosorbent assay with tumor cells.Antibodies to antigens of glial tumors were found in the blood of neurooncological patients. The highest level of antibodies was determined in the blood of patients with glioblastoma, the lowest one — with astrocytoma of II grade of anaplasia and oligodendroglioma. A weak interaction of serum of patients with glioblastoma with antigens of astrocytoma and oligodendroglioma cells was found. A high level of antibodies to antigens of glioblastomа cells reflects the intensive Th-2 specific immune humoral answer.

Prognostic Factors in Gastric Carcinoma with Peritoneal Dissemination

Objective: The prognosis for gastric carcinoma patients with peritoneal dissemination is very poor. We evaluated the survival benefit of resection and intravenous chemotherapy in these patients.Material and methods: We reviewed the hospital records of 348 gastric carcinoma patients with peritoneal dissemination seen during the period from 1986 to 2000.Results: Based on the grade of anaplasia, 76 (21.8%) were differentiated and 272 (78.2%) were undifferentiated. In the univariate analyses, the factors influencing the 5-year survival rate were histologic type, resection, and intravenous chemotherapy. Using Cox’s proportional hazard regression model, two factors were independent, statistically significant prognostic parameters: resection (risk ratio, 1.48; 95% confidence interval, 0.90-2.46; p<0.05) and intravenous chemotherapy (risk ratio, 1.68; 95% confidence interval 1.15-2.47; p < 0.01). The 5-year survival rate was higher for patients who had intravenous chemotherapy (3.6%) than for patients who did not (2.4%), and also higher for patients who underwent resection (4.8%) than for patients who did not (0%; p < 0.001).Conclusion: The results highlight the improved survivorship of gastric carcinoma patients with peritoneal dissemination who had resection and received intravenous chemotherapy, compared with those who did not. Although curative resection cannot be performed in this group of patients, we recommend performing resection and subsequent intravenous chemotherapy.

Medulloblastomas with systemic metastases: evaluation of tumor histopathology and clinical behavior in 23 patients.

To review the clinical behavior and histopathologic features of medulloblastomas that metastasize outside the central nervous systems (CNS). The authors studied 23 cases of medulloblastomas that metastasized outside the CNS. The patients included 15 males and 8 females, ages 1 to 40 years at initial diagnosis (median 8.5). Five of the patients were over 20 years of age at diagnosis. The histologic grade of anaplasia was determined for each case. Extra-CNS metastases were identified at initial presentation in four individuals and up to 11 years later in the remaining cases. Metastatic sites included bone/bone marrow (21 cases), soft tissue/lymph nodes (3 cases), and lung (1 case). In seven cases, multiple extra-CNS metastatic sites were documented. Of the patients with available clinical follow-up after metastasis, 10 died of their disease 1 to 39 months after detection of extra-CNS metastases (median 9 months), while 5 are alive 16 to 120 months after extra-CNS metastasis (median 45 months). Moderate or severe anaplasia was detected in 8 of 20 intracranial specimens (40%) and in 4 of 6 extra-CNS metastases (66%); these frequencies are higher than observed in medulloblastomas overall. Tissue from both the initial resection and subsequent recurrence or metastasis was available in six cases. The anaplasia grade was higher upon recurrence or metastasis in four of these six, consistent with tumor progression. Metastasis of medulloblastomas outside the CNS can occur after long periods of clinical remission and is associated with anaplasia in some cases. Medulloblastomas can show histologic progression on recurrence or metastasis.

Involvement of 1p36 region in two cases of adenocarcinoma of the ampulla of Vater

Cancer of the ampulla of Vater is an uncommon disease that leads to death in 60% of affected patients. There is general agreement that local spread of the tumour (T stage) is the only significant and independent prognostic factor for this cancer. Although the genetic mechanisms underlying the development of ampullary tumors are still mostly unknown because of their rarity, the genetic anomalies involved in tumor development might serve as additional prognostic markers. Cytogenetic studies may be helpful in identifying specific chromosome regions involved in these cancers. We studied two cases of poorly differentiated ampullary adenocarcinomas using conventional and molecular cytogenetics on direct preparations. The cytogenetic analysis revealed complex chromosome complements in both cases with different cell lines, rearrangements, chromosome markers, and aneuploidies. Interestingly, the involvement of the 1p36 region was a feature of both cases. The molecular studies showed an absence of high microsatellite instability (MSI) and the morphologic and immunohistochemical pattern did not suggest MSI. This study may help to characterized ampullary adenocarcinomas showing complex karyotypes, poor differentiation and poor prognosis. In these tumors, the 1p36 region may play a relevant role in the progression towards a high grade of anaplasia.

Increased human polo-like kinase-1 expression in gliomas.

PLK-1 (polo-like kinase) belongs to the family of serine/threonine kinases and is involved in spindle formation, centrosome cycles and chromosome segregation. Hence, the kinase is tightly linked to cell proliferation. We could detect immunohistochemically highly expressed PLK protein in astrocytic tumours depending on the grade of anaplasia, in commercially available human glioma cell lines (U87MG, U118MG, U138MG), in one immortalized cell culture derived from a glioblastoma patient and in a primary culture derived from a glioblastoma patient. The highest labelling of PLK-1 was demonstrated in glioblastomas. There was a significant correlation between the PLK expression and the nuclear immunoreactivity of MIB-1. PLK-mRNA, found in all tumour specimens investigated emphasizes the close correlation to proliferation and growth. Furthermore, the relation of the PLK-1 expression to the Mitogen-activated Protein Kinase Cascades was studied by applying various highly specific inhibitors. While all inhibitors minimized the cell density, only the PLCy inhibitor clearly lead to a reduced PLK-1 expression in the three cell lines U87MG, U118MG, U138MG.

Prognostic value of beta human chorionic gonadotrophin in blood serum of patients with urinary bladder tumours.

Beta human chorionic gonadotrophin levels have been assessed in blood serum of 79 patients with bladder tumours before and seven days after transurethral electroresection (TUR). With the growth grade of anaplasia and staging the mean serum beta HCG level increased. Beta HCG was a good biological marker to differentiate between superficial and deep tumours.

Patient's and doctor's delay in primary breast cancer. Prognostic implications.

In a study of 7,608 patients with primary breast cancer patient's and doctor's delay were examined in relation to age, tumour size, grade of anaplasia, and number of positive lymph nodes. The delays were arbitrarily divided into the following intervals: Short (0-14 days), intermediate (15-60 days) and long (> 60 days). The well-established patient and tumour characteristics were shown to have prognostic significance. Similarly the delays showed significant influence on survival. A long patient's delay was associated with an unfavourable outcome, as compared with a short delay. On the contrary, the prognosis was superior for patients with a long doctor's delay compared to those with a short doctor's delay. Overall, when corrected for age, the prognostic value of delay in terms of mortality increased by 24% for a long patient's delay compared to a shorter and by 13% for a short doctor's delay compared to a longer. This indicates that doctors are capable of distinguishing between more and less aggressive malignancies. The study also suggests that all sources of delays should be kept at a minimum.

Multivariate Analysis of Progression in Superficial Bladder Cancer

A total of 217 patients with superficial bladder cancer (SBC) category Ta-T1 were retrospectively analysed for tumour progression and prognostic factors; 46% of patients presented with recurrences, 13% with increasing grades of anaplasia and 12% with progression in tumour category. The mean annual index of recurrences was 0.7 +/- 0.1; 4% of patients died from tumour progression and the overall 5-year survival rate was 88% +/- 5.3. Factors that influenced progression significantly were peritumoural dysplasia, inflammatory infiltrate, residual tumour following transurethral resections, increasing grade of anaplasia and index of recurrences > 0.7. Multivariate statistical analysis revealed that only tumour category and increasing grade of anaplasia had significant prognostic value. Increasing grade of anaplasia predicts the likelihood of tumour progression with a 91% global predictive capacity. Thirty percent of patients with tumour progression did not have an increasing grade of anaplasia. Among these 87% were Ta, 50% were GI and the mean index of recurrences was 0.9. All were conservatively treated and 87% are alive. Among the patients with an increasing grade of anaplasia and tumour progression the mean index of recurrences was 1.7; 67% developed muscle infiltrating cancer and 7% metastatic spread without local progression; 64% of these patients died from cancer. An increasing grade of anaplasia affects prognosis. It defines patients with a high risk of tumour progression and tumour-related death, especially those with T1 bladder cancer.

Breast cancer prognosis is poor when total plasminogen activator activity is low

Plasminogen activator (PA) is a serine protease which exists in two forms: tissue-type (t-PA) and urokinase-type (u-PA). The total PA activity was measured in tumour extracts of 235 breast cancer patients who were followed for a median of 8.5 years after surgery. Patients were initially divided into three groups with low (< 60 units mg-1 protein), intermediate (60-300 unit mg-1 protein), or high (> 300 unit mg-1 protein) total PA activity in tumour extracts. The PA activity was not significantly associated with the recognised prognostic factors of age, menstrual status, tumour size, lymph node involvement, histologic type, grade of anaplasia, and/or vessel involvement. A significant association was found between total PA activity and the oestrogen receptor (ER) or progesterone receptor (PgR) status. Among receptor-positive tumours, a significantly greater proportion of patients had high PA activity in their tumour extracts. Breast cancer patients with low total PA activity had a significantly shorter disease-free and overall survival rate when compared to those with intermediate or high PA activity. In univariate and multivariate analyses, total PA activity (< 60 unit mg-1 vs > or = 60 unit mg-1 protein) was found to be a significant prognostic factor for disease-free and overall survival of about the same import as lymph node involvement. Furthermore, the combination of total PA activity and nodal status could be even more precise in predicting survival times and probabilities in individual patients. This retrospective study demonstrates the total PA activity is a valuable prognostic factor in determining prognosis in human breast cancer.

Short recurrence-free survival associated with high oestrogen receptor levels in the natural history of postmenopausal, primary breast cancer.

The ability of oestrogen and progesterone receptor (ER and PgR, respectively) status to discriminate recurrence-free survival (RFS) among a cohort of consecutively accrued 952 postmenopausal patients has been studied. None of the cohort members investigated were treated with adjuvant therapy. Using a graduated scale of receptor status [low, intermediate and high receptor levels (< 10 vs. 10-107 vs. > or = 108 fmol/mg cytosol protein, respectively)] instead of the more commonly used dichotomous subdivision (positive vs. negative), ER level significantly discriminated between groups of patients with long vs. short RFS. Contrary to our expectations, patients with highest ER levels have as poor a prognosis as ER-negative patients, while patients with intermediate ER levels have longest RFS. The group of patients with ER levels > or = 108 fmol/mg cytosol protein comprises 47% of the cohort. The independent significance of overexpression of ER as a prognostic factor among this patient group is demonstrated in multivariate analysis where ER level is more significant than either grade of anaplasia or tumour size. PgR status did not significantly predict RFS among these patients. While the highest ER levels predispose for poorer prognosis among postmenopausal patients, it is precisely this group that experiences greatest benefit from adjuvant treatment with tamoxifen. Thus, patients who might otherwise go untreated due to their node-negative status can be readily identified and offered adjuvant treatment.