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Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements.

The purpose of this study was to determine the independent prognostic significanceof interstitial fluid pressure (IFP) measurements in cervix cancer. A total of 102 patients with newly diagnosed cervix cancer were accrued to this prospective study. There were 31 International Federation of Gynecology and Obstetrics stage IB or IIA tumors, 40 IIB tumors, and 31 IIIB tumors. The median size was 5 cm (range, 2-10 cm). Pelvic lymphadenopathy was identified radiographically in 20 patients. IFP was measured at examination under anesthesia using a wick-in-needle technique. Multiple measurements were made in each tumor. The mean IFP in individual tumors ranged from -3 to 48 mm Hg, and the median for the entire cohort was 19 mm Hg. Treatment consisted of external beam and intracavitary radiation without chemotherapy. Median follow-up was 2.5 years. The 3-year disease-free survival of all of the patients was 53%. Disease-free survival was 34% in patients with IFP >19 mm Hg, and 68% in those with lower IFP (P = 0.002). To evaluate rigorously the independent prognostic significance of IFP measurements relative to established clinical factors, a multivariate model was first developed using stepwise selection of clinical covariates. Tumor size (P = 0.0003) and pelvic lymph node status (P = 0.0016) comprised the clinical model. IFP, when added to this model, provided additional independent prognostic information (P = 0.0013). IFP was also significant (P = 0.0027) when the clinical factors and hypoxic proportion as determined with the Eppendorf electrode were analyzed together. Patients with high IFP were more likely to recur both locally and at distant sites. This study is the first to document a strong, independent prognostic importance of pretreatment IFP measurements in cervix cancer. Patients with high IFP are significantly more likely than those with low IFP to recur after radiotherapy and die of progressive disease, independent of clinical prognostic factors and the results of tumor oxygen measurements.

Adult↗

Time independence of the prognostic impact of tumor cell detection in the bone marrow of primary breast cancer patients.

PURPOSE: Tumor cell detection (TCD) in bone marrow is an outstanding prognostic factor in breast cancer. There is only one other study that has investigated more than 300 patients with a median follow-up of more than 5 years (J. L. Mansi et al., Lancet, 354:197-202, 1999). We report data from 727 patients with a median follow-up period of 6.5 years. EXPERIMENTAL DESIGN: In a prospective study, intraoperatively aspirated bone marrow was screened for micrometastatic cancer cells. We used an immunocytological method (monoclonal mucin antibody 2E11; the avidin-biotin complex method). RESULTS: Forty-three percent of the patients were TCD positive. Sixty percent of the patients with distant metastases were tumor cell positive (155 of 258 patients). Forty-nine percent of the patients with positive TCD developed distant metastases (155 of 315 patients). TCD was an independent prognostic factor for clinical outcome after a median follow-up time of 6.5 years. The prognostic impact of TCD and tumor size remains constant with the time, whereas the impact of grading and progesterone receptor on risk seems to decrease with longer follow-up time. CONCLUSIONS: TCD remains an independent prognostic factor The impact of TCD does not change with longer follow-up time. TCD is a reliable prognostic factor and provides important information about the process of metastasis.

Adult↗

[Multivariate analysis of prognostic factors in Philadelphia chromosome-positive chronic granulocytic leukemia].

OBJECTIVE: To investigate the prognostic factors of the patients with Philadelphia chromosome-positive chronic granulocytic leukemia (CGL). METHODS: Clinical and laboratory parameters of 209 CGL patients at diagnosis were analyzed in relation to survival. COX regression analysis were used to identify the statistically significant prognostic factors. RESULTS: The median survival time was 57 (3 - 179) months, and 5 year survival rate was 48%. From the COX regression model, the four main poor prognostic factors were as follows: percentage of bone marrow blasts (>or= 0.04), percentage of peripheral blood blasts and promyelocytes and presence of erythroid precursors in peripheral blood. According to the prognostic scores, three groups of CGL were identified. The low-risk group was with a median survival time of 76 months, the intermediate-risk group with 56 months, and the high-risk group with 31.5 months (P < 0.01). The 5 year survival rate was 70.42%, 46.30% and 18.18% (P < 0.01), respectively. CONCLUSIONS: A prognostic scoring system suitable for Chinese CGL patients was proposed.

Adolescent↗

CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer.

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of cancer-related mortality in Taiwan. We became interested in searching for the factors predictive of survival. Serum CA19-9 (carbohydrate antigen 19-9) level has been reported as a factor predictive of survival in patients with colorectal cancer. A few articles have reported that patients with metastatic colorectal cancer who have normal (< or = 37 U/mL) serum CA19-9 levels survived significantly longer than those with higher serum CA19-9 levels. However, these reports are contradictory and lack definite conclusions. This study was carried out in an effort to evaluate the prognostic significance of serum CA19-9 levels in patients with metastatic colorectal cancer in Taiwan. METHODOLOGY: Between 1991 and 1994, a total of 128 patients with histologically confirmed metastatic colorectal cancers were evaluated retrospectively at Veterans General Hospital-Taipei. All patients had measurable metastatic lesions and life expectancies of more than 3 months. 5-Fluorouracil-based chemotherapy, either in a weekly bolus regimen or a monthly 5-day bolus schedule, were administered to all of them. Data on age, sex, performance status, location of primary tumor, extent of metastases, site of metastases, histological differentiation, serum CEA (carcinoembryonic antigen) and CA19-9 levels were analyzed before chemotherapy to determine their association with survival. Blood samples for CEA and CA19-9 measurement were analyzed using the radioimmunoassay method. Multivariate analysis by the Cox's proportional hazards regression model was performed to determine independent prognostic factors among all of the possible variables. RESULTS: By univariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.022) were identified as prognostic factors, while age, sex, location of primary tumor, site of metastasis, histological differentiation, and pre-treatment serum CEA levels were not considered significant. By multivariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.014) were still found as independent prognostic factors of these patients. CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.

Adenocarcinoma↗

Prognostic value of Catterall and Herring classification in Legg-Calvé-Perthes disease: follow-up to skeletal maturity of 32 patients.

To compare the prognostic value of the Catterall and Herring classification, 32 patients, treated without surgery for unilateral Perthes diseases, were reviewed and classified at skeletal maturity according to Stulberg. The Catterall classification had no significant prognostic correlation with the final outcome. Only some head at-risk signs, such as lateral epiphyseal calcification and epiphyseal subluxation >4 mm, were prognostic. The Herring lateral pillar was not predictive when it was considered alone, but it became prognostic when related to age at onset. Moreover, in group C of the Herring classification (lateral pillar <50%), the final outcome was better in children younger than 6 years. This last observation strengthens the opinion that age and related residual skeletal moulding are also of prognostic value in Perthes disease.

Child↗

Prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection: univariate and multivariate analysis.

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma is clinicopathologically distinct from hepatocellular carcinoma and hilar cholangiocarcinoma, and the prognostic factors after hepatic resection of these rare tumors are not well documented. The aim of this study was to evaluate prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection. METHODOLOGY: We retrospectively studied 20 consecutive patients with intrahepatic cholangiocarcinoma who underwent hepatectomy over a 15-year period from 1984 to 1998. Fifteen prognostic factors were evaluated for their association with overall and disease-free survivals in univariate and multivariate analysis (Cox's proportional hazards model). RESULTS: Eighty percent of the resected patients had major hepatectomy. Operative morbidity and mortality rates were 30% and 0%, respectively. Four patients (20%) survived more than 5 years without recurrence after hepatic resection. The 1-year, 3-year, and 5-year overall or disease-free survival rate after hepatic resection were 56.0% or 49.5%, 43.8% or 43.3%, and 43.8% or 37.3%, respectively. Univariate analysis showed young age and periductal invasion tumor or the presence of vascular invasion, lymphatic invasion, and lymph node metastasis as significant poor prognostic predictors contributing overall and disease-free survivals. Multivariate analysis revealed only lymph node metastasis as an independent prognostic factor affecting disease-free survival. During the same time, 17 unresectable patients were treated by intrahepatic arterial infusion chemotherapy (12), systemic chemotherapy (4), or radiation (1). Median overall survival time in resected patients (16 months) was significantly better than in unresectable patients (5 months) (P = 0.005). CONCLUSIONS: Hepatic resection remains to be the best current therapeutic option. The prognosis after hepatic resection for intrahepatic cholangiocarcinoma was determined by lymph node metastasis. New adjuvant chemotherapy after surgery is imperative for such patients.

Aged↗

[Prognostic and therapeutic aspects of catathymis delusions].

The prognostic and therapeutic aspects of catathymic delusional formations, excluding those associated with organic psychoses, are comprehensively presented from five points of view: (1) the present possibilities of psychiatric prognostication; (2) prognostic implications of nosological classifications; (3) prognostic significance of nosographic characteristics; (4) relationship to general rules of psychiatric prognostics; (5) therapautic points. Under (3) we report our own findings concerning the long-term development of delusional formations and the long-term course of delusional illnesses classified as 'schizophrenia of late onset'; we report their relationships to the formation of defect syndromes and to the psycho-organic deterioration in old age.

Delusions↗

Difference in prognostic factors between stage IB and II uterine cervical carcinoma patients treated with radical hysterectomy and postoperative radiation therapy.

PURPOSE: The purpose of the current study was to evaluate the difference in prognostic factors between stage IB and II uterine cervical carcinoma patients treated with postoperative radiation therapy. PATIENTS AND METHODS: Between May 1988 and May 1998, a total of 94 patients including 47 patients with stage IB and 47 patients with stage II uterine cervical carcinoma were treated with postoperative radiation therapy at Tokyo Metropolitan Komagome Hospital. All patients were treated with 10 MV X-rays using an anterior-posterior parallel opposed field which covered the whole pelvis. Fractionation was 2 Gy per day, five fractions per week, to a total dose of 50 Gy. RESULTS: The 5-year overall survival rates of stage IB and II were 89.4% and 79.3%, respectively. In multivariate analysis for all patients, lymph node status, histology, and surgical margin status were recognized as prognostic factors. Limited to stage IB patients, lymph node status was the only independent prognostic factor. However, for stage II patients, tumor histology was also an independent prognostic factor. CONCLUSIONS: The prognostic factors of stage IB and II were different. Tumor histology was only associated with stage II patients. These findings suggested that tumor histology might have played a different role as tumor stage progressed. However, further studies with large numbers of patients will be required to confirm these results.

Adult↗

Prognostic and predictive value of epidermal growth factor receptor in recurrent breast cancer.

PURPOSE: The prognostic and predictive value of epidermal growth factor receptor (EGFR) expression was evaluated in patients with recurrent breast cancer. EXPERIMENTAL DESIGN: The immunohistochemical expression of EGFR was analyzed in 241 patients with recurrent breast cancer. RESULTS: EGFR expression was positive in 87 of 241 (36%) patients with recurrent breast cancer, whereas the EGFR expression inversely correlated with the estrogen receptor (ER) status. The patients with positive EGFR expression had a significantly worse postrelapse survival than those with a negative EGFR expression, whereas EGFR expression also had a postrelapse prognostic significance in patients with a positive ER status. A multivariate analysis indicated EGFR expression to be an independently significant factor for postrelapse survival, whereas a multivariate analysis in which the ER status was added to variables indicated that ER status but not EGFR expression to be an independently significant factor. There was a significant difference between positive and negative EGFR expression in the treatment response of 82 patients who received hormonal therapies and 374 patients who received chemotherapies, whereas a multivariate analysis indicated the responses to the first-line treatment and EGFR expression to be independently significant factors for postrelapse survival. CONCLUSIONS: EGFR expression had prognostic significance in recurrent breast cancer, whereas its prognostic value was not independent of the ER status. In addition, the EGFR expression was suggested to be related to the responses to hormonal therapy and chemotherapy, whereas the EGFR expression had an additional prognostic value that was independent of the treatment response.

Adult↗

Comparison of prognostic scoring system to tumor node metastases 1992 and 1997 staging systems in gastric cancer patients.

Tumor node metastases staging systems have been widely utilized to predict the prognosis of gastric cancer patients. The current study aimed to compare a prognostic scoring system to tumor node metastases 1992 and 1997 staging systems in predicting the outcome of resectable gastric cancer patients. Patients treated between 1996-1998 were retrospectively evaluated. Tumor depth in the gastric wall, anatomical location and number of metastatic lymph nodes, metastatic to retrieved lymph node ratio, extent of surgical resection, tumor location, type of lymph node dissection, macroscopic appearence and histologic type of tumor were recorded and patients were divided into groups I-III due to their scores. Patients were also staged according to both tumor node metastases systems. Survival data was analyzed by Kaplan-Meier method. For the comparison of power of the three systems in predicting survival, log-rank and Cox regression analysis were respectively used for univariate and multivariate analysis. 163 resectable gastric cancer patients were evaluated. Median follow-up and survival times were 26 and 23 months respectively. Overall 5-year survival was 37.6%. The number of patients in prognostic scoring groups I, II and III was 44, 109 and 10, respectively. According to tumor node metastases 1992 system, 13, 43, 101 and 6 patients were in stages I, II, III and IV while there were 13, 38, 78 and 34 patients in respective stages in tumor node metastases 1997 system. Although tumor node metastases 1992 (p=0.0088), 1997 (p=0.0029) and prognostic scoring systems (p=0.0006) significantly predicted the survival of patients in univariate analysis, prognostic scoring system was found to be superior compared to other two systems in multivariate analysis (p=0.0002). Prognostic scoring system is a practical, reliable and reproducible method that could be used as an adjunct to tumor node metastases systems in predicting survival of resectable gastric cancer patients.

Adult↗

[Renal cell carcinoma before the age of 40: prognostic factors].

OBJECTIVE: To study the prognostic value of tumour diameter, TNM stage, Führman's nuclear grade and CD44 adhesion molecule expression in renal cell carcinoma (RCC) before the age of 40 years. MATERIAL AND METHODS: Nineteen patients under the age of 40 (12 males and 7 females; mean age 30.8 years), undergoing total nephrectomy for RCC were included in this study. Tumour diameter, TNM 1997 stage, and Führman's nuclear grade were defined for each tumour. Standard CD44 adhesion molecule (CD44H) expression was evaluated semiquantitatively by immunohistochemistry on each tumour. The prognostic value of the various variables was determined by Mann-Whitney and Chi-square tests and survival analysis was performed by the Kaplan-Meier method. RESULTS: Six patients (31.5%) died from their cancer with a mean follow-up of 81.4 months. Mean tumour diameter was 9 +/- 4.5 cm. Tumours were Führman I/II in 4 cases, Führman III/IV in 15 cases, T1/T2 in 14 cases and T3/T4 in 5 cases. CD44H expression was high (> or = 20%) in 9 cases (47.3%). The prognostic factors identified in this study were: tumour stage (p = 0.01), grade (p = 0.04), venous extension (p = 0.001) and CD44H overexpression (p = 0.003). CONCLUSION: Prognostic factors of renal cancer in patients under the age of 40 years do not appear to be different from those of older patients. The prognostic factors identified in this study must be validated by multicentre studies based on larger populations.

Adult↗

[Prognostic factors for deep situated malignant gliomas treated with linac radiosurgery].

BACKGROUND & OBJECTIVE: Though radiosurgery has been used for more than 10 years, the value of radiosurgery for malignant glioma has not been clarified. This paper was designed to investigate efficacy of radiosurgery to malignant glioma by analyzing the prognostic factors affecting prognosis of malignant gliomas treated with linac radiosurgery. METHODS: Fifty-eight patients with deep situated malignant gliomas, 28 anaplastic astrocytomas(AA) and 30 glioblastomas (GBM), aged from 7 to 70 years, were analyzed. The mean volume of tumor was 12.08 cm3, and mean prescription dose for linac radiosurgery was 19.42 Gy. The results were analyzed with Kaplan-Meier curve and Cox regression. RESULTS: There were 44.8% of the tumors shrank. Median tumor local control interval was 10 months(15 months for AA and 9 months for GBM). Tumor local control probability was 37.9% for 1 year and 10.3% for 2 years. Median survival was 22.5 months for AA and 13 months for GBM and 15 months for all patients. The survival probability was 79.3% at 1 year and 20.6% at 2 years. Isocenter numbers and tumor volume were the prognostic factors for tumor control, but conformity index was prognostic factor for survival as determined by Cox regression analysis. Considered of pathology, only isocenter number and target volume significantly affected the tumor control interval. Complication appeared in 44.8% of the patients and the median interval of complication onset was 8 months. Symptomatic cerebral edema was observed in 31.0% of the patients. CONCLUSION: Linac radiosurgery can effectively improve tumor local control and elongate survival for the patients with deep situated malignant gliomas. Tumor volume is the prognostic factor for tumor control, while conformity index is prognostic factor for survival.

Adolescent↗

The prognostic value of polymorphonuclear leukocyte elastase in patients with primary breast cancer.

A variety of serine proteases, including urokinase-type plasminogen activator (uPA), plasmin,and polymorphonuclear leukocyte elastase (PMN-E), have been implicated in the processes of tumor cell invasion and metastasis. Besides degrading of matrix proteins, PMN-E has been shown to be able to cleave and inactivate plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of uPA, and alpha2-antiplasmin, the natural inhibitor of plasmin, thus enabling an uncontrolled matrix degradation by the fibrinolytic enzymes. Because only limited data are available on a relationship between the tumor level of PMN-E and prognosis in primary breast cancer patients, in the present study we have measured with an ELISA the levels of PMN-E (in complex with alpha1-proteinase inhibitor) in cytosolic extracts of 1143 primary breast tumors. Levels of complexed PMN-E have been correlated with the lengths of metastasis-free survival (MFS), relapse-free survival, and overall survival, and a comparison was made with data previously obtained for uPA and PAI-1. Our results show that patients with a high PMN-E level in their primary tumor had a rapid relapse and an early death compared with patients with a low tumor level of PMN-E. This held true for node-negative and node-positive subgroups of patients as well. The relationship of PMN-E with a poor prognosis was especially obvious during short-term follow-up (0-60 months). In Cox multivariate regression analysis, corrected for the traditional prognostic factors, PMN-E was an independent prognostic factor, and high levels of PMN-E were associated with a poor MFS [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.23-2.16; P < 0.001], relapse-free survival (HR, 1.45; 95% CI, 1.10-1.89; P = 0.01), and overall survival (HR, 1.64; 95% CI, 1.20-2.23; P = 0.003). Furthermore, in all three multivariate models, PMN-E still added significantly to the model after the additional inclusion of the uPA. PMN-E was an independent prognostic factor for MFS even in the multivariate analysis including the traditional clinical prognostic factors and the strong established biochemical prognostic factors uPA and PAI-1. Our present study suggests that PMN-E is associated with breast cancer metastasis, and knowledge of the tumor PMN-E status might be helpful in selecting the appropriate individualized (adjuvant) treatment for patients with breast cancer.

Adult↗

Prognostic significance of expression of p53 oncoprotein in primary (stage I-IIIa) non-small cell lung cancer.

Mutation of the p53 gene is one of the most common genetic abnormalities found in all types of human cancer. Accumulating evidence strongly indicates that p53 alterations play a role in tumorgenesis in non-small cell lung cancer (NSCLC). However, the role of p53 as a prognostic marker in NSCLC remains unclear. The data derived from the literature on prognostic impact of p53 in NSCLC has been a matter of controversy. Among the reasons for the discrepancy, are lack of correlation with key clinical parameters, patients with different stages, different antibodies used, and insufficient sample size. The intent of this study was to evaluate the prognostic value of p53 protein in a larger cohort of stage I-IIIa patients. Clinicopathological data was obtained on 179 patients with NSCLC. These data were correlated with the p53 status on the respective surgically resected tumors, using monoclonal antibody DO7. There is a significant relationship between strong p53 expression and patient survival. In a multivariate analysis, strong expression (> 50%) of the p53 oncoprotein is an independently favorable prognostic factor. Patients with strong p53 expression had a prolonged survival (p = 0.009, RR; 0.56, 95% CI: 0.35-0.86). The median time of survival for patients with strong and negative/weak p53 expression was more than 61 and 44 months, respectively. The present study suggests that p53 protein expression in tumor tissue may serve as a prognostic biomarker for NSCLC. This information may also potentially serve as a tool for clinical decision-making when selecting patients for adjuvant treatments of NSCLC.

Adult↗

Older age and second skin cancer as prognostic factors in localized malignant melanomas.

Of the numerous prognostic factors for patients with localized malignant melanoma (LMM), none is superior to the simple parameter of tumor thickness. The aim of the present study was to better define prognostic factors for this disease. Between January 1992 and December 1994, 188 consecutive patients with LMM were treated at the Rabin Medical Center. Patient and tumor characteristics were retrospectively examined as potential prognostic factors. Patients (n=173) who had had at least two-year follow-up were included in the overall survival (OS) analysis, and 159 patients for whom accurate data on recurrent disease were available were included in the disease-free survival (DFS) analysis. At a median follow-up of 85 months (range 24-114), 48 patients (30%) had recurrent disease which resulted in death in 35 (20%). The five-year OS and DFS rates for the entire group were 82 and 72%, respectively. On univariate analysis, female gender, age younger than 75 years, metachronous or synchronous second skin cancer (including melanoma), light skin color, tumor thickness and TNM stage were predictive of both OS and DFS. Tumor location and ulceration, correlated with only one endpoint, OS or DFS, respectively. On multivariate analysis, three factors retained statistical significance with regard to both OS and DFS: tumor thickness (p=0.000 for both), second skin cancer (p=0.02 for both), and age (p=0.04 for both). Alongside the well-established predictive factor of tumor thickness in LMM, older age and the presence of a second skin cancer also have prognostic significance. The prognostic importance of the latter is reported here for the first time.

Adolescent↗

Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM) frequently involves amplification and alteration of the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of varied mutations, including the most common mutation, EGFRvIII, as well as wild-type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively analyzed the relationship between treatment outcomes and the EGFR gene in 87 newly diagnosed adult patients with supratentorial GBM enrolled in clinical trials. The EGFR gene status was assessed by Southern blots and EGFR expression by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR, EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in 40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed. On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no EGFR overexpression was present. There was a close correlation between EGFR amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in 27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P < 0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR amplification was an independent, significant, unfavorable predictor for overall survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the relationship of age to EGFR prognostication, the EGFR gene status was a more significant prognosticator in younger patients, particularly in those <60 years (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII overexpression, on the other hand, was not predictive for OS. However, in patients with EGFR amplification, multivariate analysis revealed that EGFRvIII overexpression was an independent, significant, poor prognostic factor for OS (P = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the presence of EGFR amplification is the strongest indicator of a poor survival prognosis. In GBM patients, EGFR is of significant prognostic value for predicting survival, and the overexpression of EGFRvIII with amplification plays an important role in enhanced tumorigenicity.

Adolescent↗

Microvessel density as a prognostic factor in preinvasive and invasive cervical lesions.

OBJECTIVE: To assess angiogenesis in preinvasive and invasive cervical lesions and its prognostic value in squamous cell carcinoma (SCC). METHODS: Twenty-seven cervical intraepithelial lesions (CIN I, II and III), 27 Stage Ib-IIa SCC and 12 normal cervical epithelium were included in the study. Clinico-pathological prognostic factors were re-evaluated from the patients' files and previous tissue sections. Microvessel density (MVD), a marker for angiogenesis, was assessed from new tissue blocks by an immunohistochemical staining method. Statistical tests included Kruskall-Wallis analysis, the Mann-Whitney U-test, Fisher's exact t-test to analyse the categorical data and Cox regression and Kaplan-Meier survival analyses to define the effect of prognosticators on survival. RESULTS: CIN II and III lesions had significantly higher MVD counts than normal epithelium and CIN I lesions, both of which had similar MVD count. Compared to preinvasive lesions invasive SCC had significantly higher MVD counts. Among SCC cases, only pelvic lymph node involvement appeared to be independent risk factor on unvariate analysis. However, MVD, as a cut-off value of 21 determined by ROC analysis, was found to be an independent prognosticator in early stage SCC cases by multivariate analysis. CONCLUSION: Despite the small number of enrolled cases, the results of this study suggest that angiogenesis involved in the development and progression of cervical neoplasms and MVD might be used as a prognostic factor.

Adult↗

DNA methylation in serum of breast cancer patients: an independent prognostic marker.

Changes in the status of DNA methylation are one of the most common molecular alterations in human neoplasia. Because it is possible to detect these epigenetic alterations in the bloodstream of patients, we investigated whether aberrant DNA methylation in patient pretherapeutic sera is of prognostic significance in breast cancer. Using MethyLight, a high-throughput DNA methylation assay, we analyzed 39 genes in a gene evaluation set, consisting of 10 sera from metastasized patients, 26 patients with primary breast cancer, and 10 control patients. To determine the prognostic value of genes identified within the gene evaluation set, we finally analyzed pretreatment sera of 24 patients having had no adjuvant treatment (training set) to determine their prognostic value. An independent test set consisting of 62 patients was then used to test the validity of genes and combinations of genes, which in the training set were found to be good prognostic markers. In the gene evaluation set we identified five genes (ESR1, APC, HSD17B4, HIC1, and RASSF1A). In the training set, patients with methylated serum DNA for RASSF1A and/or APC had the worst prognosis (P < 0.001). This finding was confirmed by analyzing serum samples from the independent test set (P = 0.007). When analyzing all 86 of the investigated patients, multivariate analysis showed methylated RASSF1A and/or APC serum DNA to be independently associated with poor outcome, with a relative risk for death of 5.7. DNA methylation of particular genes in pretherapeutic sera of breast cancer patients, especially of RASSF1A/APC, is more powerful than standard prognostic parameters.

Adult↗