Percutaneous ethanol injection under general anesthesia for hepatocellular carcinoma: 3 year survival in 112 patients

OBJECTIVE: The aim of this study was to determine whether the expression of thymidine phosphorylase by ovarian cancer cells correlates with the density of microvessels within the tumor, and with ultrasound-derived indices of blood flow. METHODS: Transvaginal ultrasonography with color Doppler imaging and pulsed Doppler spectral analysis was used to scan patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of thymidine phosphorylase and the intratumoral density of microvessels by immunohistochemistry using monoclonal antibodies to thymidine phosphorylase and factor VIII-related antigen, respectively. The main outcome measures were the histological classification of the tumor, the stage of the disease, whether or not the tumor cells were positive or negative for thymidine phosphorylase, the microvessel count and the peak systolic velocity (PSV). RESULTS: Forty-two tumors were studied (three of low malignant potential, 29 epithelial, four granulosa cell, two germ cell and four metastatic); 18 were stage I, six stage II, 11 stage III and three stage IV. Twenty-seven tumors (64%) were classified as thymidine phosphorylase-positive. The proportion of stage I tumors that was thymidine phosphorylase-positive (44%) was significantly lower (p = 0.022) than the corresponding value for stages II-IV (85%), but the values for microvessel count and PSV were similar. The microvessel count in thymidine phosphorylase-positive tumors was significantly higher than in thymidine phosphorylase-negative tumors (p = 0.005). Similarly, the PSV was significantly higher in thymidine phosphorylase-positive tumors (p = 0.009). There was a significant correlation between the microvessel count and the PSV (r = 0.354, p = 0.022). CONCLUSIONS: The expression of thymidine phosphorylase by malignant tumor cells is associated with an increase in microvessel density and PSV in patients with ovarian cancer.     

Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes staging

Tumor angiogenesis is associated with metastasis in several types of solid tumors, including melanoma, breast, prostate, lung, bladder, and oral-cavity tumors. The purpose of this study was to determine whether tumor angiogenesis could predict recurrence following curative surgery for colorectal cancer. Thirty-five patients were studied, including 13 patients with recurrent tumor and 22 without. Representative formalin-fixed, paraffin-embedded sections of invasive colorectal cancers from these patients were sectioned. The endothelial cells of microvessels within the tumors were highlighted by immunohistochemical staining for CD31. The most active areas were identified and the microvessels counted in a x 400 field (0.152 mm2) by two observers in a blinded fashion. Tumor microvessel count (p = 0.0062). Dukes' staging (p = 0.0004), vascular invasion (p = 0.0280), and tumor grade (p = 0.0559) were all significantly associated with tumor recurrence. Tumor microvessel counts > or = 65 per x 400 field were associated with tumor recurrence (p = 0.0035, relative risk [RR] = 11.3). Controlling for Dukes' stage, a multivariate logistic regression model revealed that a tumor microvessel count > or = 65 is an important predictor of tumor recurrence (p = 0.0783, RR = 6.0). A backwards elimination proportional hazards model revealed that a microvessel count > or = 65 shows a trend toward independent prediction of time to tumor recurrence (p = 0.1203, RR = 2.967) when controlled for Dukes' staging (p = 0.0029, RR = 9.089). Despite the small number of patients studied, these results suggest that the number of microvessels in sections of invasive colorectal adenocarcinoma immunohistochemically stained with CD31 may be an important independent predictor of tumor recurrence and time to recurrence.     

The effects of FR167653 in extended liver resection with ischemia in dogs

PURPOSE: We assess the neovascularity of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody CD34 in an attempt to identify associations between angiogenesis and disease progression following radical prostatectomy. MATERIALS AND METHODS: Microvascularity was evaluated using the CD34 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 149 patients followed from 3 to 10 years (mean 6.6). Vessels were quantified by counting a minimum of 2 selected microscopic fields (200x, 0.754 mm.2) from each tumor, area of prostatic intraepithelial neoplasia and prostatic hyperplasia, and given a numerical value representing the microvessel density count. RESULTS: Mean microvessel density count did not vary significantly with age or race. There was a significant association between the count and nuclear grade, Gleason sum and pathological stage. Cox survival analysis shows that microvessel density is significantly related to time to recurrence when considered as a continuous variable (p=0.03) as well as dichotomous variable (p=0.007) (microvessel density count less than 90 and 90 or greater). The 5-year recurrence-free survival was significantly higher for patients with a count less than 90 (71%) than for those with a count 90 or greater (51%) (p=0.006). The 5-year recurrence-free survival was also significantly different when microvessel density was used as a continuous variable (p=0.02). Controlling for stage, Gleason sum, race and nuclear grade, microvessel density remained significant in predicting recurrence (p=0.03) but when pretreatment prostate specific antigen was included in the model the count was no longer significant. The microvessel density count in the tumor area significantly increased with increasing Gleason sum and nuclear grade but it did not increase significantly in the adjacent benign prostate or areas of prostatic intraepithelial neoplasia in the same specimen. CONCLUSIONS: Microvascularity or neovascularity as measured by the CD34 antigen may be a prognostic marker of recurrence for prostate cancer patients after radical prostatectomy but more study in prostate specific antigen era patients with sufficient followup is needed.     

Significance of angiogenic factors in liver metastatic tumors originating from colorectal cancers

We examined the expression of vascular endothelial growth factor (VEGF) and microvessel counts expressed by CD34 staining in 39 patients with primary and 44 patients with metastatic liver tumors of metastatic colorectal carcinoma, and 29 patients with nonmetastatic colorectal carcinoma as control in order to determine their value in the evaluation of prognosis and recurrence after hepatectomy. Microvessel counts in primary colorectal carcinomas of the metastatic group were significantly higher than those in control (P<0.05). Neither factor correlated with any clinicopathological feature of primary or metastatic liver carcinomas. Higher microvessel counts in metastatic liver tumors tended to be associated with a shorter disease-free interval to second recurrence in the remaining liver (P = 0.069) and were significantly associated with poor prognosis after hepatectomy (P<0.05). We conclude that microvessel count is an important marker of liver metastasis and prognosis in patients with colorectal carcinoma treated with hepatectomy.     

Tumor angiogenesis as a prognostic factor in ovarian carcinoma: quantification of endothelial immunoreactivity by image analysis

BACKGROUND: The growth of a malignant tumor requires the formation of new capillaries. Quantification of these microvessels is difficult. The purpose of this study was to establish an objective technique for quantifying angiogenesis and to evaluate whether microvessel quantity may predict tumor aggressiveness in patients with ovarian carcinoma. METHODS: Endothelial area was used to quantify microvessel density in immunohistochemically stained sections of 28 International Federation of Gynecology and Obstetrics Stage IIIC ovarian carcinomas. The endothelial area was measured with a computer-aided image analysis system in the subepithelial stroma of highest vascularization. The endothelial area in the specimens of 14 patients who survived for > or =6 years was compared with that of 14 patients matched for stage and treatment who died of the disease. RESULTS: The mean tumor area analyzed was 5.04 +/- 0.23 mm2. The mean endothelial area per mm2 of stroma from survivors and dead patients was 0.038 +/- 0.026 mm2 and 0.110 +/- 0.034 mm2, respectively (P < 0.0001). No significant differences were found in histology, tumor grade, status of lymph nodes, and amount of residual tumor. CONCLUSIONS: Image analysis was used to overcome the potential subjectivity of manual counts. Computer-assisted image analysis can evaluate accurately the angiogenic potential in ovarian carcinomas. Tumor angiogenesis may prove to be a prognostic factor in patients with ovarian carcinoma. This study suggests that the measurement of the endothelial area would be clinically useful in determining microvessel density [See editorial on pages 2219-21, this issue.]     

Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D

In order to investigate the changes in glycoprotein structure between non-metastatic and metastatic cells of nasopharyngerl carcinoma (NPC), peanut agglutinin (PNA), ulex europeaus (UEA-I) and concanavalin ensifomis agglutinin (ConA) staining were used to examine 102 nasopharyngeal carcinoma tissues (84 primary tumors and 18 metastatic lymph nodes) with the avidin-biotinperoxidase complex method. PNA reaction was positive in most cells of nasopharyngeal carcinomas regardles of in histopathologic type, the degree of differentiation and metastasis. The levels of UEA-I receptors apparently increased during nasopharyngeal carcinoma progression from non-metastatic to metastatic tumors. The binding to ConA clearly decreased in the cells of metastatic cases and metastatic lymph node. So, the increased expression of UEA-I receptors and decrease of ConA receptors on tumor cells might have been implicated in the expression of metastatic potential.     

BAL fluid contains detectable superoxide dismutase 1 activity

We retrospectively analyzed the prognostic significance of angiogenesis and the relationships between tumor angiogenesis and clinopathological variables in a series of 127 patients with primary esophageal squamous cell carcinoma which were curatively resected. Vessels were stained with anti-factor VIII polyclonal antibody and areas with the highest number of microvessels were counted in a x400 field. Microvessel counts were significantly correlated with pN category, pM category, venous invasion and recurrence (p=0.002, p=0.040, p=0.016 and p=0.0013, respectively). The proportion of patients with recurrence increased in proportion to the number of microvessels. multivariate analysis using Cox's proportional hazard modelling showed angiogenesis assessed by microvessel count affected the poorer prognosis of patients with esophageal squamous cell carcinoma (hazard ratio, 1.03; 95%CI, 1.00-1.07), although it was not a significant independent prognostic factor (P=0.088). This study suggest that angiogenesis assessed by microvessel count is a marker for relapse and prognosis in patients with esophageal squamous cell carcinoma.     

A morphometric study of neovascularization in colorectal carcinoma

BACKGROUND: Neovascularization reportedly is correlated with metastasis, recurrence, and prognosis in some types of tumors. Microvessel quantification in so-called "hot spots" has been studied extensively as the only factor reflecting angiogenesis in various malignant tumors. The objective of this report was to evaluate multiple morphometric microvascular characteristics in addition to microvessel density (MVD) in colorectal carcinomas to provide a better approach to examining the relation between angiogenesis and clinicopathologic factors and prognosis. METHODS: Histologic sections from 106 colorectal adenocarcinomas and 17 adenomas, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to the vessel size or shape. RESULTS: MVD gradually decreased with progressing Dukes stage. The vascular branching counts were significantly higher in carcinomas than in adenomas, and remained unaffected through progressing Dukes stages. Shape-related parameters showed significant differences between carcinomas and adenomas and between different grades of differentiation. Branching counts and TVA were the only factors found to be of prognostic significance. CONCLUSIONS: This study provides evidence that neovascularization is an early critical event in colorectal tumorigenesis, reaching a maximum level early in the malignant process. Its prognostic significance is better assessed by quantification of TVA and the branching pattern of microvessels, whereas MVD does not provide significant prognostic information for colorectal carcinoma patients.     

Lymph node size does not correlate with the presence of prostate cancer metastasis

Prostate carcinoma (PC) is the second leading cause of cancer death in men in the western world. Although the role of oncogenes and growth factors in prostate carcinoma is still unclear, overexpression of the epidermal growth factor receptor (erbB-1) and the proto-oncogene erbB-2 have been reported in prostate tumors, and erbB-2 related to poor prognosis and distant metastasis. Recent allelotyping studies in prostate cancer have shown chromosomal gains in 7p and 17q, regions where erbB-1 and erbB-2 are localized respectively, although no direct evidence of an increased gene copy number of either erbB-1 or erbB-2 has been reported. To address this question, we analyzed 20 benign prostatic hyperplasia (BPH) samples and 36 samples of metastatic and non-metastatic PC by means of semiquantitative PCR. Thus, 64% (11/17) and 52% (10/19) of metastatic and non-metastatic tumors respectively showed gains of the relative genomic content of erbB-1 and an association of erbB-1 with prostate cancer but not with metastasis. Additionally, 41% (7/17) of metastatic samples showed gains of erbB-2 genomic content, suggesting an association of erbB-2 with metastasis and poor prognosis (p<0.005). No gains of erbB-1 or erbB-2 genomic content were detected in the BPH samples.     

Angiogenesis as a predictor of survival after surgical resection for stage I non-small-cell lung cancer

OBJECTIVES: Some patients with surgically resected stage I non-small-cell lung cancer eventually have metastatic disease. A histologic marker of metastatic potential and diminished survival for stage I non-small-cell lung cancer may distinguish this patient population. This study evaluates the degree of angiogenesis as a predictor of cancer-related death after operation for stage I non-small-cell lung cancer. METHODS: Demographic, surgical, and histopathologic data, including presence of vascular invasion, were reviewed for 106 patients with stage I non-small-cell lung cancer from 1985 through 1990. Visual quantitation of microvessels immunostained with factor VIII-related antigen and CD31 in 5 microm sections from the paraffin blocks of tissue defined rumor angiogenesis. RESULTS: Follow-up was 95.1% complete, mean 5.2 +/- 3.0 years. Lung cancer-related mortality rate was 24.4% at 5 years. Mean microvessel counts were 20.7 +/- 11.2 for FVIII and 29.6 +/- 18.1 for CD31. Univariate analysis revealed an FVIII count of at least 20 (p = 0.025) and blood vessel invasion (p = 0.017) to be significant predictors of disease-related death. After adjustment for other patient and tumor characteristics, multivariate Cox regression analysis found an FVIII count of at least 20 (hazard ratio 2.9) and blood vessel invasion (hazard ratio 3.7) to be significant independent correlates of lung cancer death (p = 0.018 and p = 0.011, respectively). CD31 quantitation did not predict survival on univariate or multivariate analyses and did not correlate strongly with FVIII quantitation (Spearman's rank correlation r = 0.19). CONCLUSIONS: This analysis reveals a significant association between tumor neovascularization and cancer-related mortality rate among patients with stage I non-small-cell lung cancer. Microvessel quantitation of FVIII, as an indicator of tumor angiogenesis and metastatic potential, may define a subset of patients with stage I non-small-cell lung cancer who could benefit from adjuvant therapy after surgical resection.     

nm23 in the primary and metastatic sites of gastric carcinoma. Relation to AFP-producing carcinoma

Tumor metastasis is the major cause of treatment failure and death in cancer patients. The present study was designed to extrapolate the association of nm23 expression with acquisition of metastatic potential of gastric carcinoma with special reference to the alpha-fetoprotein-producing gastric carcinoma (APGC). The primary tumor with surrounding normal mucosa and metastatic lymph nodes of 30 patients with APGC and 29 randomly selected matched controls of non-AFP gastric carcinoma (NAGC) were immunostained for nm23 and an image analyzer system was used for quantitative evaluation. Overexpression of nm23 was noted in 71% (42/59) of the primary tumors and 18% (10/55) of the metastatic tumors and there was no difference between the APGC and NAGC groups. The overexpression of nm23 in the primary tumors correlated with tumor invasion, metastasis and progression in all cases and similar results were obtained in the APGC and NAGC groups except for the tumor stage which was insignificant in the APGC group. The patient survival was adversely affected by the overexpression of nm23 in the primary sites and downregulation in the metastatic sites in all cases but lost their significance in the multivariate analysis. However, nm23 status did not affect patient survival in the APGC group.     

Adenovirus-mediated p16 transfer to glioma cells induces G1 arrest and protects from paclitaxel and topotecan: implications for therapy

This study evaluated Epstein-Barr virus (EBV) DNA in sera of 42 patients with nasopharyngeal carcinoma (NPC) and 82 healthy individuals who had been infected previously with EBV. Thirteen of 42 NPC samples were positive for EBV DNA in their sera, whereas all 82 normal controls were negative. In addition, EBV typing between primary tumors and sera showed identical results, suggesting that serum EBV DNA represented tumor DNA. To evaluate the importance of the serum NPC DNA, clinical data and tumor phenotypes including age, sex, WHO type, EBV type, stage, tumor invasion, metastasis, and apoptosis were correlated with serum EBV DNA, and only apoptosis was found statistically significant. In conclusion, EBV DNA was detectable in the serum of some patients with NPC, represented tumor DNA, and might have clinical implications in the future.     

Surgical analysis for metastatic lung tumor from renal cell carcinoma

Metastatic lung tumor from renal cell carcinoma were studied in 29 cases. Eighteen patients were treated surgically, 11 were treated non-surgically. The overall 5-year survival rate with the patients of pulmonary resection was 53.5%, and that with those of conservative therapy was 0%, and this difference is statistically significant (p < 0.05). There was no significant difference in any characteristics such as sex, age, stage, grade, disease free interval, metastatic pattern and combination with or without interferon therapy. There was no significant difference in surgically treated patients with pulmonary metastasis in terms of any factors such as age, sex, stage, grade, disease free interval, pulmonary metastasis pattern, metastatic number, surgical procedure, combination with or without interferon therapy statistically. Analysis for the surgically treated patients with pulmonary metastasis from renal cell carcinoma shows no significant difference in prognosis with any characteristics. This result shows efficacy of surgery even if for the patients with synchronous bilateral multiple pulmonary metastasis from renal cell carcinoma.     

CD44H expression by human neuroblastoma cells: relation to MYCN amplification and lineage differentiation

The human CD44 cell surface glycoprotein has been involved in a variety of functions including lymphocyte homing, extracellular cell matrix attachment, and tumor metastasis. Due to the alternative splicing of the single gene, a large family of different variants or isoforms is generated. Several reports have indicated an up-regulation of CD44 variant (v) isoforms in malignant process, conferring metastatic potential to non-metastatic cells. Neuroblastoma is a tumor characterized by an aggressive and metastatic behavior in advanced stages with amplification of the MYCN protooncogene. In this report we show that the CD44 standard molecule is highly expressed in 100% of stage I-III, IVs neuroblastomas and ganglioneuromas but only in a subset of stage IV tumors. In contrast, no expression of CD44 was detected on MYCN amplified stage IV tumors, thus demonstrating a highly significant negative relationship between MYCN amplification and CD44 expression in neuroblastoma. The expression of CD44 on neuroblastoma cultured cell lines was not shown to be related to MYCN amplification but rather linked to the S-type, schwann/glial differentiation lineage. Immunochemical analysis of tumor samples with anti-CD44v3 and -v6 antibodies and Northern blot analysis of mRNA from cell lines with probes spanning exons 4-10 did not reveal any expression of splice variants on neuroblastomas of all stages and cell lines, thus ruling out a major role of these isoforms in neuroblastoma progression and metastasis.     

Influence of adhesion molecule expression by human brain microvessel endothelium on cancer cell adhesion

Cultures of endothelial (En) cells derived from human brain microvessels were established in order to characterize adhesion molecule expression and to assay the adhesion properties of neoplastic cell lines to monolayers of En cells. Low constitutive expression of beta1 integrin (CD29), and ICAM-2 (CD102) was detected on human brain microvessel En cells. The beta1 chain of the VLA integrin family, ICAM-1, E-selectin (CD62E) and VCAM-1 (CD106) but not ICAM-2 and PECAM-1 (CD31) expression was upregulated by IL1-alpha, and TNF-alpha proinflammatory cytokines. High expression of PECAM-1 was found on non-activated human brain EN cells. In order to study the potential role of adhesion molecules in neoplastic cell adhesion two tumor cell lines were chosen. Adhesion of a cell line (DU145) derived from a cerebral metastasis of prostate carcinoma to human brain microvessel En cell monolayers was less pronounced compared to adhesion of a primary prostate carcinoma cell line (ND1). Adhesion of cerebral metastatic neoplastic cell line (DU145) was not significantly influenced by incubation of endothelial cells with different proinflammatory cytokines. The adhesion capability of primary prostate carcinoma line (NDI) was significantly upregulated by TNF-alpha proinflammatory cytokine. Furthermore, the adhesion of ND1 was partly inhibited using anti-E-selectin and VCAM-1 monoclonal antibodies. There was no significant effect of anti-adhesion antibodies on the adhesion characteristics of the cerebral metastatic (DU145) cell line. Our data demonstrate that different mechanisms are involved in the adhesion of neoplastic cells to cerebral En cells and turn our attention to the importance of adhesion molecule expression in the formation of metastases.     

Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis

Matrix metalloproteinase (MMP) expression is associated with advanced-stage cancer and contributes to tumor progression, invasion, and metastasis. Membrane type matrix metalloproteinase (MT-MMP) has a potential transmembrane domain at the C terminus and activates pro-MMP-2, which is mainly produced from interstitial fibroblasts. Its expression on the membrane of invasive tumor cells results in the pericellular space degradation at cell-matrix contact sites and renders cancer cells more invasive at the migration front. To elucidate the relationship between MT-MMP expression and metastasis and prognosis in gastric cancer patients, MT-MMP expression was analyzed immunohistochemically in 127 primary tumors and results were correlated with several prognostic parameters and patient's survival. MT-MMP immunoreactivity was stained on the cell membrane of cancer cells and fibroblasts in the invasion front. MT-MMP was detected in 72 tumors (57%) (MT-MMP-positive). MT-MMP expression was closely associated with macroscopically invasive type, nodal involvement, lymphatic invasion, vessel invasion, and peritoneal dissemination. Patients with MT-MMP-positive tumor had a significantly worse prognosis than those with MT-MMP-negative tumor (p<0.001). Multivariate analysis showed MT-MMP overexpression as an independent prognostic factor in gastric cancer patients. Immunohistochemical analysis for MT-MMP may be an indicator of metastatic potential or the prognosis of gastric cancer patients.     

The role of chemotherapy in the management of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy (RT). However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor. METHODS: A review of retrospective and prospective clinical studies was performed to assess the role of chemotherapy in three settings: metastatic disease; neoadjuvant and/or adjuvant; and concurrent chemotherapy with radiotherapy. RESULTS: Cisplatin-based combination chemotherapy results in a high response rate in patients with metastatic NPC, and a subgroup may achieve long term disease free survival. The use of neoadjuvant and adjuvant chemotherapy to treat locoregionally advanced disease has resulted in consistently high response rates, but no randomized trial to date has demonstrated an improvement in overall survival. A recent Head and Neck Intergroup study randomized patients in the United States to receive concurrent chemotherapy (cisplatin) and radiotherapy or radiotherapy only. Although this approach demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy, its applicability in geographic areas of high NPC incidence remains to be proven. CONCLUSIONS: NPC is a chemosensitive tumor, and patients with metastatic disease have a high response rate. Further prospective studies will define the standard approach to treating locoregionally advanced NPC, which is likely to incorporate into the primary treatment some form of systemic chemotherapy.     

A novel concept in mucosal adjuvanticity: the CTA1-DD adjuvant is a B cell-targeted fusion protein that incorporates the enzymatically active cholera toxin A1 subunit

OBJECTIVE: To examine the relationship between the expressions of glutathione S-transferase pi (GST-pi) and four oncogene products, c-Jun, c-Fos, c-H-Ras, and c-Myc, and clinicopathological prognostic factors and patients' prognosis in endometrial carcinomas, and to assess their prognostic value in endometrial carcinomas. METHODS: Specimens of endometrial carcinoma obtained from 63 patients were investigated immunohistochemically using respective specific antibodies. RESULTS: The overall positive rates in 63 carcinoma specimens were 34.9% for GST-pi, 44.4% for c-Jun, 34.9% for c-Fos, 47.6% for c-H-Ras, and 54.0% for c-Myc. Multivariate analysis revealed that GST-pi expression correlated independently with paraaortic lymph node (PAN) metastasis, and c-Jun expression was independently related to pelvic lymph node (PLN) and PAN metastasis. The prognosis of patients with a GST-pi-positive tumor was significantly poorer than that of those with a GST-pi-negative tumor (P < 0.05). The patients with c-Jun-positive tumor also had a significantly worse prognosis than those with c-Jun-negative tumor (P < 0.05). No significant relationship between the expressions of the remaining three oncogene products, c-Fos, c-H-Ras, and c-Myc, and the examined prognostic factors and clinical outcome was apparent. CONCLUSION: These results suggest that the expressions of GST-pi and c-Jun may reflect the metastatic potential of endometrial carcinomas and that their expressions of endometrial carcinoma may be useful as a prognostic indicator for predictive testing.     

Carcinoma of the cervix: predictive value of clinical and magnetic resonance (MR) imaging assessment of prognostic factors

PURPOSE: This retrospective study assesses the predictive value of magnetic resonance imaging (MRI) to identify high risk cervical cancer patients. METHODS AND MATERIALS: The MRI evaluation of morphologic risk factors in patients with invasive cervical carcinoma treated with definitive radiation therapy were correlated with clinical factors and with complete tumor regression (CTR) at 6 months, tumor local control (TLC), and patient outcome at 12 months after irradiation. Sixty-six patients, median age 44.5 years, with bulky Stage I or greater disease were included in the study. RESULTS: In univariate analysis, clinical International Federation of Gynecology and Obstetrics (FIGO) stage had significant correlation with patient outcome, but it correlated poorly with complete tumor regression and tumor local control. In contrast, MRI stage showed significant correlation with complete tumor regression, tumor local control, and disease-free survival at 12 months. When each stage was analyzed separately, the greatest difference was demonstrated between clinical and MRI assignment of stage Ib disease. MRI Stage Ib disease significantly correlated with all three categories analyzed, while clinical Stage Ib did not. Superiority of MRI assessment of low stage disease was also evident in the detection of lymph node metastasis. Significant risk for nodal metastasis was related to tumor size greater than 4 cm, invasion of the parametria and urinary bladder, and stage of the disease. CONCLUSION: The multivariate analysis demonstrated that the most related variables in order of significance were the presence of juxta-regional and paraaortic lymph nodes, patient age, tumor size, and MRI tumor stage. This study demonstrates the value of MR imaging as an adjunct to clinical assessment of bulky invasive cervical cancer, rendering more complete assessment of morphologic risk factors important in patient prognosis.     

Computer-assisted image analysis of intratumoral vessel density in mammary tumors from dogs

OBJECTIVE: To determine whether intratumoral microvessel density can be used to distinguish benign from malignant mammary tumors in dogs and to predict the outcome of surgical treatment for small volume (< 3-cm diameter) tumors. SAMPLE POPULATION: Tissue sections from 58 mammary tumors (42 malignant and 16 benign) from dogs. PROCEDURE: Mammary tumors were stained by immunohistochemistry for factor VIII-related antigen. Computer-assisted image analysis was used to determine intratumoral vessel density in immunostained areas. Total vascular density (TVD), calculated from 3 non-overlapping fields, was analyzed for correlation with patient or tumor histomorphologic characteristics, and results obtained by surgical treatment of small volume tumors. RESULTS: Mean TVD of malignant tumors was significantly greater than that of benign tumors. Total vascular density was not correlated with patient age, sex, reproductive status, clinical tumor stage, or histologic type. For small volume (< 3-cm diameter) malignant tumors, mean TVD was higher in tumors that recurred after surgery than in tumors that did not recur; however, TVD was not predictive of time to recurrence. CONCLUSION AND CLINICAL IMPLICATIONS: Immunohistochemistry and computer-assisted image analysis allowed objective quantitation of intratumoral microvessel density in formalin-fixed, paraffin-embedded tissue sections. Tumors with high TVD were more likely to recur after surgical treatment than tumors with low TVD suggesting that TVD measurements can be used by the clinician, in addition to histologic type and clinical stage, to predict prognosis after surgical treatment. These data also provide rationale for use of antiangiogenesis strategies for treatment of malignant mammary tumors in dogs.