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PubMed2002

Prognostic indicators of IgA nephropathy in the Chinese--clinical and pathological perspectives.

BACKGROUND: IgA nephropathy is the most common primary glomerulonephritis in the world. Up to 30% of patients can progress to end-stage renal disease (ESRD) in 10 years. METHODS: We studied 168 Chinese patients with IgA nephropathy followed for an average of 7.4 years in our hospital and tried to identify the clinical and pathological data that were associated with the prognosis of the disease. Clinical features at the time of renal biopsy were reviewed. Severity of histological involvement was scored semi-quantitatively as grade 1-3. RESULTS: There was a female preponderance in our cohort of patients (male:female ratio 1:1.5). The average age at biopsy was 32.9+/-10.0 years. Forty-seven of the 168 patients (28.0%) were hypertensive and 47 of 136 patients (34.6%) had a family history of hypertension. A high histological grade of IgA nephropathy was associated with hypertension at presentation, family history of hypertension, a higher serum creatinine, total cholesterol and 24-h urine protein excretion, and a lower serum albumin level. During the follow-up period, four patients died and another 24 progressed to ESRD. The renal survival was 92.0% at 1 year, 87.5% at 5 years and 81.8% at 10 years. With univariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation (plasma creatinine >120 micromol/l), high cholesterol, proteinuria >1 g/day and high histological grading were associated with poor prognosis. With multivariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation, proteinuria >1 g/day and histological grading were independent predictors of renal survival. The relative risks of renal failure for patients were 9.60 (95% confidence interval 4.02-22.92) with hypertension, 1.56 (1.16-2.02) with a family history of hypertension, 15.38 (6.40-36.93) with renal impairment and 5.93 (3.07-11.46) with every increase of one histological grade. Male patients did not show a more adverse outcome compared with females. CONCLUSIONS: Our results suggest that renal biopsy remains useful, even in clinically trivial disease, because of its distinct value in prognosis and risk stratification. The long-term prognosis of IgA nephropathy in Chinese patients is guarded. The prognostic importance of family history of hypertension has not been widely recognized and requires further study.

Adolescent↗
PubMed1992

Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer.

BACKGROUND: It has been reported that 50%-70% of patients with bladder cancer experience recurrence after initial successful treatment and about 10%-20% of these patients die of the disease. Despite precise pathologic staging and grading, we are unable to predict clinical outcome in all patients. The retinoblastoma-susceptibility (RB) gene, a prototype of tumor suppressor genes, has recently been associated with development and/or progression of bladder cancer, as well as sarcoma and small-cell lung cancer. In transitional cell carcinomas of the bladder, we have observed altered expression of the Rb gene product--a nuclear phosphoprotein thought to function as a cell cycle regulator. PURPOSE: The aim of this study was to investigate the hypothesis that altered patterns of Rb expression correlate with prognosis in bladder cancer. METHODS: Expression of the RB gene was evaluated in specimens from 48 primary bladder tumors obtained by cystectomy or transurethral resection. Rb protein expression was correlated with disease outcome in these patients. Rb expression was examined by immunohistochemistry, using the mouse monoclonal antibody Rb-PMG3-245 on frozen tissue sections. Computerized image analysis was used to quantify the level of Rb protein in individual tumor cells. RESULTS: The overall 5-year disease-free survival was 66%, with a median follow-up of 42 months. Normal levels of Rb protein expression were found in 34 patients (Rb-positive group). A spectrum of altered patterns of expression from undetectable levels to heterogeneous expression, however, was observed in 14 patients (altered Rb group). Of the 38 patients with muscle-invasive tumors, 13 were categorized as having altered expression of Rb protein. Only one of 10 patients with superficial carcinomas had altered expression of Rb protein. The 5-year survival was significantly decreased in patients with altered Rb protein compared with the survival in patients with positive Rb expression (P less than .001). CONCLUSIONS: The results suggest that tumors exhibiting decreased expression of the RB gene-coded product (Rb protein) had a more aggressive biological behavior than those that expressed the Rb protein in the majority of their tumor cells. IMPLICATIONS: This study demonstrates that altered patterns of Rb protein expression may be an important prognostic variable in patients presenting with invasive bladder cancer.

Adult↗
PubMed2003

Laminin gamma2-chain fragment in the circulation: a prognostic indicator of epithelial tumor invasion.

Laminin (LN) 5, the major component of epithelial-derived extracellular matrix (ECM), plays a major role in cell adhesion and motility. Previous reports stated that proteolytic processing of the NH(2)-terminal region of the gamma2 chain enhances cell motility on LN5, indicating that the degraded gamma2 chain NH(2)-terminal region would be shed from the ECM. However, soluble LN gamma2 NH(2)-terminal fragment (G2F) have not been detected in biological fluids. Here, we developed a double-monoclonal electrochemiluminescence immunoassay for human G2F and detected its presence in the normal human circulation (mean +/- SD: 39.2 +/- 10.3 ng/ml; n = 10). We also measured serum levels of G2F in nude mice orthotopically transplanted with three different human pancreatic carcinoma cell lines: MIApaca-II (secreting no LN5), HPAC (secreting the alpha3beta3gamma2 heterotrimer of LN5), or KP-1 (secreting the monomeric gamma2 chain of LN5). Serum levels of G2F drastically increased in the nude mice transplanted with HPAC (mean +/- SD: 351 +/- 33 ng/ml, 5 weeks after transplantation), the most invasive tumor cells to generate extensive peritoneal dissemination in vivo. A moderate increase in serum levels of G2F was also observed in mice transplanted with KP-1 (87.9 +/- 82 ng/ml, 5 weeks after transplantation), but no antigen was detected in the sera of MIApaca-II-transplanted mice. Therefore, circulating G2F was demonstrated to be a sensitive marker for LN5 production of primary pancreatic carcinomas, even if it was produced only as a monomeric gamma2 chain. In 11 established human pancreatic tumor cell lines (6 of LN5-producing cells and 5 of nonproducing cells), LN5-secreting cells have significantly higher levels of cell surface expression of beta4 integrin than nonsecreting cells. Thus, LN5 secretion is accompanied by cell surface expression of alpha6beta4 integrin, participating in hemidesmosome reorganization to form invading edges of malignant epithelial carcinomas. These data reveal that the level of circulating G2F is a new, prognostic, tumor-characterizing marker for estimating the invasiveness and malignancy of epithelial carcinomas in cancer patients.

Adenocarcinoma↗
PubMed2004

Noninvasive in vivo detection of prognostic indicators for high-risk uveal melanoma: ultrasound parameter imaging.

PURPOSE: Primary malignant melanoma of the choroid and ciliary body has traditionally been treated without histologic staging, using purely clinical indicators. The presence of extravascular matrix patterns (EMP) in histologic sections of uveal melanoma has been shown to be an independent indicator of metastatic risk. These patterns are of a dimension and physical composition that are likely to be detected with ultrasound backscatter analysis. Our aim was to determine whether ultrasound parameter imaging could detect the presence of EMP at a diagnostically significant level for treatment staging and for planning investigational studies of therapeutic modalities. DESIGN: Prospective, masked ultrasound-pathologic correlative study. PARTICIPANTS: One hundred seventeen patients diagnosed with previously untreated choroidal melanoma were scanned within 2 weeks before enucleation. METHODS: Tumors were evaluated histologically and divided into high-risk and low-risk groups on the basis of the presence of 2% or more histologic cross-sectional area composed of EMP patterns. Digital ultrasound data were processed to generate parameter images representing the size and concentration of ultrasound scatterers. Histologic and ultrasound images and data were correlated, and linear and nonlinear statistical methods were used to create multivariate models for noninvasive differentiation of high-risk and low-risk tumors. MAIN OUTCOME MEASURES: Presence or absence of high-risk EMP and associated ultrasound parameter classification models. RESULTS: Of the 117 tumors, 69 were classified as low risk, and 48 were classified as high-risk with histologic analysis. A classification that used ultrasound parameter image features with linear discriminant analysis could correctly identify 79.5% of cases retrospectively and 75.2% of cases by use of cross-validation, an estimate of prospective classification ability. By use of a more powerful classification technique (support vector machine), 93.1% of cases were correctly classified retrospectively. With a cross-validation procedure, 80.10% of cases were correctly classified. CONCLUSIONS: Ultrasound can be used noninvasively to classify tumors into high-risk and low-risk groups by detecting the presence of EMP patterns. By the use of previous studies that compared the histologic presence of EMP patterns with patient survival, estimates of hazard rates associated with ultrasound risk groups can be made. The noninvasive ultrasound classification is potentially useful as a prognostic variable and as a tool for stratification of patient populations for tumor treatment evaluation.

Eye Enucleation↗
PubMed1997

Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study.

BACKGROUND: Tumors acquire nutrients that are essential for continued growth and an avenue for dissemination to the rest of the body by inducing angiogenesis (i.e., the formation of new blood vessels). Preliminary studies involving a number of different kinds of cancer have indicated that an assessment of tumor angiogenesis may be useful in predicting disease outcome. PURPOSE: In a prospective study, we evaluated the relationship between tumor angiogenesis and survival for 407 patients with non-small-cell lung carcinoma who were treated with potentially curative surgery. METHODS: The study population consisted of 360 male and 47 female patients who underwent surgery consecutively at the Department of Surgery, University of Pisa, Italy, from March 1991 through December 1994. Follow-up lasted through February 1996, with a median follow-up for living patients of 29 months (range, 15-60 months). An anti-CD34 monoclonal antibody, which is specific for endothelial cells, and standard immunohistochemical techniques were used to measure angiogenesis in tumor samples. Angiogenesis was quantified in terms of microvessel counts; the counts for single, high-power microscopic fields (magnification x250) in the three most intense areas of blood vessel growth for each sample were averaged. The median microvessel count in this series was 20, and the counts were categorized as follows: 1) low versus high (< or =20 versus >20 microvessels) or 2) in five categories (1-10, 11-20, 21-30, 31-40, and > or =41 microvessels). Disease-free and overall survival during follow-up were assessed. Kaplan-Meier survival curves were modeled in a univariate analysis of patient and tumor characteristics; the Cox proportional hazards model was used in multivariate analysis. Reported P values are two-sided. RESULTS AND CONCLUSIONS: In the univariate analysis, patients with larger tumors (P for trend <.00001), a more advanced tumor stage (P for trend <.00001), a greater degree of regional lymph node involvement (P for trend <.00001), or more vascularized tumors (high versus low microvessel count, P<.00001) experienced significantly reduced overall survival. When microvessel counts were analyzed in five categories, a highly significant trend (P<.00001) toward worse prognosis was observed with increasing tumor vascularity. In multivariate analysis, tumor microvessel count (P<.00001), tumor size (P = .0006), and regional lymph node status (P<.00001) retained independent prognostic value with respect to overall survival; among these variables, tumor microvessel count, considered as a continuous variable, was the most important, with a relative hazard of death of 8.38 (95% confidence interval = 4.19-16.78) associated with the highest microvessel counts. IMPLICATIONS: An evaluation of tumor angiogenesis may be useful in the postsurgical staging of patients with non-small-cell lung carcinoma and in identifying subsets of patients who may benefit from different postsurgical treatments.

Adult↗
PubMed2005

Breast cancer: steroid receptors and other prognostic indicators.

OBJECTIVE: To correlate hormone receptor status in breast cancer with patient's age, tumor size, type, grade and lymph node metastasis. DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Histopathology, Liaquat National Postgraduate Medical Center, Karachi, from January 2002 to March 2003. PATIENTS AND METHODS: One hundred and fifty patients of breast cancer were studied. Estrogen and progesterone receptor status was evaluated by immunohistochemistry. This was correlated with patients' age, tumor size, type, grade and lymph node status. RESULTS: Out of 150 cases, 55% of cases were estrogen receptor (ER) negative progesterone receptor ( PR) negative. Older women tended to have more steroid receptor reactivity as compared with younger ones. ER positivity decreased with increasing tumor size and grade, however, no significant correlation was seen with lymph node metastasis. Majority of the tumors showing ERPR positivity were infiltrating ductal carcinoma-not otherwise specified type. CONCLUSION: This study reports a significantly higher incidence of ER negative PR negative phenotype in breast cancer patients. This observation is different as compared with that in western literature where ER positive PR positive phenotype is greater than the negative phenotype suggesting that breast cancer in our patients may have different disease pattern and biology.

Biomarkers, Tumor↗
PubMed1981

Prognostic indicators of herpetic keratitis. Analysis of a five-year observation period after corneal ulceration.

Clinical features of 152 patients with herpetic keratitis after a five-year observation period were analyzed. When compared with dendritic ulceration, geographic ulcers that had been symptomatically present for a longer time were more likely to have been treated with a topical steroid and took longer to heal. After treatment of the corneal ulceration, 40% of the patients experienced a recurrent herpetic ulcer, 25% experienced disciform or irregular stromal keratouveitis, 5% experienced ocular hypertension, and 6% had a decrease in visual acuity caused by corneal scarring. Recurrent ulcerative herpetic keratitis occurred more frequently in men and in patients who entered the study with a history or previous herpetic ulceration.

Adolescent↗
PubMed1989

Prognostic indicators in head and neck cancer patients receiving combined therapy.

In 1983 we initiated a prospective nonrandomized study of the value of preoperative chemotherapy in previously untreated patients with stages III and IV squamous cell carcinoma of the head and neck. In 1983 and 1984, 50 patients were entered in the study. Prior to therapy all patients were evaluated by a representative from the Medical Oncology, Radiation Therapy, and Head and Neck Surgery Divisions, University of Utah School of Medicine, Salt Lake City. In addition to the standard preoperative evaluation, pretreatment computed tomographic scans were performed on all patients. Follow-up computed tomographic scans were performed after the second cycle of chemotherapy and at the completion of treatment. Initial therapy in all patients consisted of induction chemotherapy with cisplatin (day 1, 100 mg/m2) and fluorouracil (days 1 through 5, 1000 mg/m2). Several factors were examined for their utility in predicting response to therapy and survival. Factors evaluated included: (1) extent and timing of chemotherapeutic response; (2) computed tomographic quantitated primary tumor size; (3) size of computed tomographic quantitated regional (neck) metastases; (4) performance status; (5) cancer stage; (6) total lymphocyte count; and (7) serum liver function tests. The factor found to be most useful in predicting improved survival was the extent of response to chemotherapy. The remaining factors, performance status, regional lymph node status, serum gamma-glutamyltransferase levels, and cancer stage, were also found to correlate with length of survival but were much less important than the response to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1975

Serum prognostic indicators in experimental Bacteroides peritonitis.

Serum lysozyme and hemolytic complement (CH100) levels were measured in dogs with experimental Bacteroides peritonitis. The CH100 levels showed little change in surviving animals. Nonsurvivors showed a moderate decrease in complement levels shortly after contamination. Both surviving and nonsurviving animals showed a slight initial decrease in lysozyme levels shortly after contamination. In surviving dogs this was followed by an increase to normal levels. In nonsurvivors, levels continued to increase, reaching a threefold magnification just prior to death. As a result of antibiotic therapy, CH100 levels exhibited no major changes; however, dogs deprived of antibiotic showed noticeable and persistent increases in lysozyme levels while treated animals showed only a mild elevation in lysozyme levels. The changes in the level of serum lysozyme may be a good indicator of antibiotic efficacy and approaching death from Bacteroides peritonitis.

Animals↗
PubMed1996

Are argyrophilic nucleolar organizer regions good prognostic indicators of survival of patients with esophageal cancer with lymph node metastasis?

Argyrophilic nucleolar organizer regions (AgNORs) were evaluated in 95 samples from primary esophageal squamous cell carcinomas and 75 samples from metastatic lymph nodes. The number of AgNORs per nucleus in primary tumors with positive nodes (n=53, 6.1+/-1.8) was greater than that in primary tumors with negative nodes (n=42, 3.8+/-1.1, P<0.001). In 39 of 53 patients with positive nodes, the numbers of AgNORs per nucleus in metastatic lymph nodes were lower than those in primary tumors. The 5-year survival rate of these patients was 23.7%. However, the numbers of AgNORs per nucleus in metastatic lymph nodes were greater than those of primary tumors in 14 of 53 patients with positive nodes, and 11 of these 14 patients died from recurrence of cancer within 3 years after surgery. These observations suggest that the proliferative activity of cancer cells might be suppressed in the regional lymph nodes. However, cancer cells with higher proliferative activity in the regional lymph nodes than in the primary tumors might overcome immunological defenses and subsequent further metastasis might occur.

Aged↗
PubMed1997

Tumor size as a prognostic indicator of histologic grade of soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: Tumor size is one of the independent factors affecting prognosis of patients with soft tissue sarcoma (STS). We evaluated the significance of tumor size in combination with tumor depth in each histologic grade. METHODS: A total of 162 adult patients with localized STS in the extremities and trunk were selected. Patient ages ranged from 15 to 84 (median 46.5) years with a male-to-female ratio of 1.19. Histologic grade of tumors was low in 53 cases, intermediate in 51, and high in 58. Two types of categorization were set, and their significance in predicting the prognosis of patients in each grade was evaluated. In the first category (intermediate grade), tumors were dichotomized at 10 cm: Group A comprised patients with deeply seated tumors measuring > 10 cm; Group B comprised patients other than those in Group A. In the second category (high grade), tumors were dichotomized at 5 cm: Group C comprised patients with deeply seated tumors measuring > 5 cm; Group D comprised patients other than those in Group C. RESULTS: Categorization was not useful in the prognosis of low grade tumors. In the intermediate grade group, the 5-year-survival rate of Group B patients (78%) was higher than in Group A patients (59%) (P < 0.05), showing that dichotomization at 10 cm was useful. In the high grade group, the 5-year survival rate in Group C patients (32%) was lower than in Group D patients (56%), showing that dichotomization at 5 cm was useful. CONCLUSIONS: These findings show that tumor size for the prognosis of patients with STS differs according to each histologic grade.

Adolescent↗