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Prognostic indicators for poor risk epithelial ovarian carcinoma.

BACKGROUND: The objective of this study was to identify factors that categorize patients with epithelial ovarian carcinoma into favorable and unfavorable prognostic groups at the time of initial treatment. METHODS: Data were analyzed from 51 women who were treated at Yale University, had an evaluable CA 125 half-life (t1/2), and were followed for disease recurrence for at least 2 years. RESULTS: Grade, maximum level of CA 125, and histology did not provide useful prognostic information. Stage, residual disease, minimum CA 125, and CA 125 t1/2 individually were predictive of persistent disease or recurrence within 3 years of diagnosis with sensitivities of 97, 70, 34, and 49%, respectively, and specificities of 33, 83, 100, and 83%, respectively. When these factors are combined, defining an unfavorable prognostic group as those patients having residual disease greater than 1 cm, CA 125 t1/2 greater than 12 days, or minimum CA 125 never falling below 35 U/ml, sensitivity and specificity were 96 and 65%, respectively, at 1 year of follow-up and 91 and 75%, respectively, at 3 years of follow-up. 75%, respectively, at 3 years of follow-up. CONCLUSIONS: In those patients in whom residual small volume disease after primary surgery indicates a good prognosis, minimum CA 125 and CA 125 t1/2 during chemotherapy can further categorize patients into favorable and unfavorable prognostic groups.

Antigens, Tumor-Associated, Carbohydrate↗

DNA ploidy and the percentage of cells in S-phase as prognostic factors for women with lymph node negative breast cancer.

BACKGROUND: Previous cell kinetic studies have shown that the percentage of cells in S-phase (%S) of the tumor may be an important prognostic factor for relapse-free survival (RFS) and overall survival (OS) in patients with resected lymph node negative breast cancer. METHODS: This study examined DNA ploidy and %S from the paraffin embedded primary tumors of 265 patients who had surgery between 1975 and 1981, had lymph node negative cancer, and had no adjuvant therapy. The %S and %G2M values were calculated using a debris and aggregate subtraction model. RESULTS: The results of the DNA ploidy analysis revealed 130 (49%) DNA diploid tumors and 135 (51%) DNA nondiploid tumors. Ploidy was not significant for either RFS (P = 0.20) or OS (P = 0.13). The total %S (using a cutoff of 8%) was a statistically significant prognostic factor for RFS (P = 0.003) and borderline for OS (P = 0.08). The proliferation fraction (%S + %G2M), using a cutoff of 12.5, was a statistically significant prognostic factor for RFS (P = 0.01) and for OS (P = 0.01). In a Cox multivariate analysis for RFS, the total %S remained significant (P = 0.05) along with tumor size. In the analysis of OS, the proliferation fraction remained significant (P = 0.03) along with tumor size and age. DNA ploidy was not significant in any multivariate analysis. CONCLUSIONS: This study suggests that tumor size and cell proliferation parameters are independent prognostic factors for patients with resected lymph node negative breast cancer. However, the clinical usefulness of the cell kinetic parameters appears limited.

Adult↗

Urokinase plasminogen activator as a prognostic marker in different subgroups of patients with breast cancer.

BACKGROUND: Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. Previously, uPA was shown to be an independent prognostic marker in breast cancer. The aim of this study were to evaluate uPA as a prognostic marker in different subgroups of patients with breast cancer. METHODS: Urokinase plasminogen activator was assayed by enzyme-linked immunosorbent assay in detergent extracts of human breast tumors. RESULTS: Using both disease free interval (DFI) and overall survival (OS) as end points, uPA was an indicator of prognosis in the following groups of patients: those with positive axillary nodes, those who were estrogen receptor (ER)-positive, women younger than 50 years of age, and women older than 50 years of age. For patients with negative axillary lymph nodes, uPA was a significant prognostic marker using DFI as an end point and was almost statistically significant (P = 0.055) using OS as end point. In patients who were ER-negative, uPA levels showed no significant relationship with patient outcome. CONCLUSIONS: Urokinase plasminogen activator is a significant prognostic marker in most of the major subgroups of patients with breast cancer and may be a marker for patients with negative axillary lymph nodes.

Animals↗

Prognostic significance of serum antibodies to human papillomavirus-16 E4 and E7 peptides in cervical cancer.

BACKGROUND: The objective of this study was to investigate the prognostic significance of serum antibodies to human papillomavirus (HPV)-16 peptides in patients with squamous cell cervical cancer. METHODS: Pretreatment sera from 78 patients and 198 control women were tested by an enzyme-linked immunosorbent assay technique for reactivity with HPV-16 E4 (E401p) and E7 (E701p) synthetic peptides. The presence and serum level of these antibodies were correlated with tumor stage, histologic features, and prognostic parameters. RESULTS: The median follow-up was 65 months (range, 6-97 months). Antibodies to E401p peptide were found in 5 of the 198 (3%) control subjects, 4 of the 43 (9%) patients with low tumor stage (International Federation of Gynecology and Obstetrics [FIGO] Ia, Ib, IIa), and 7 of the 35 (20%) patients with advanced tumor stage (FIGO IIb, III, IVa). Antibodies to E701p were found in 25 (13%), 11 (26%), and 11 (31%) women, respectively. The differences between patients and control subjects were significant (P < 0.002). Seropositivity against these peptides showed no correlation with tumor stage. Antibody levels to both peptides were significantly higher in patients compared with control subjects (P < 0.05). Furthermore, antibody levels to E401p were higher in patients with advanced tumor stage versus patients with low tumor stage (P = 0.0097). Such a relation was not found for anti-E701p antibodies. In the univariate analysis, a high level of anti-E701p antibodies was associated with a shorter disease free interval (P = 0.012) and poor survival (P = 0.049). However, this variable possessed no prognostic value after adjusting for FIGO stage and tumor size. CONCLUSIONS: The authors' findings indicate that the prognostic significance of serum antibodies to the HPV-16 E4 and E7 peptides used in this study of patients with cervical cancer is limited.

Adult↗

Prognostic significance of lymph node variables in squamous cell carcinoma of the vulva.

BACKGROUND: In patients with squamous cell carcinoma of the vulva, lymph nodal, surgicopathologic variables have been studied rarely, although lymph node status is by far the most important prognostic factor. This study was designed to investigate surgicopathologic variables of lymph node metastases to evaluate their prognostic significance. METHODS: In 75 patients with inguinal and/or pelvic lymph node metastases from squamous cell carcinoma of the vulva, the following parameters were studied: size and location of the tumor, depth of invasion, grade, lymph-vascular space involvement (LVSI), local immune reaction, presence and degree of dystrophic changes in the surrounding skin, FIGO stage, number of positive lymph nodes, greatest dimension of the metastasis within the lymph node, percentage of lymph node replacement, number of lymph nodes with replacement greater than 50%, number of lymph nodes replaced completely by tumor, extracapsular spread, and active immunologic response within the lymph node. RESULTS: Among the variables related to the primary carcinomas, only size of the tumor and LVSI were correlated with survival (P < 0.003 and P < 0.02, respectively). On the contrary, all pathologic variables regarding the lymph nodes significantly influenced survival by univariate analysis. On multivariate analysis, extracapsular spread was the most significant independent prognostic factor (P < 0.0004), followed by FIGO stage (P < 0.03). For patients with only one positive lymph node, the most important prognostic factor was the greatest dimension of the metastasis within the lymph node (P < 0.01). CONCLUSIONS: These data, if confirmed in larger series, can contribute to a more accurate identification of low and high risk patients and, therefore, to a more appropriate employment of adjuvant therapies.

Adult↗

Malignant melanoma of the vulva. Evaluation of prognostic factors with emphasis on DNA ploidy in 75 patients.

BACKGROUND: To the authors' knowledge, the potential prognostic value of DNA ploidy in vulvar melanoma has not been evaluated in previous series. METHODS: Clinical data and follow-up information were retrieved from the hospital records of 75 patients treated from 1956 to 1987. Histopathologic specimens were reviewed for histologic type, depth of invasion, vessel invasion, and ulceration. Flow cytometric DNA measurements were performed on paraffin embedded samples. RESULTS: Forty-three patients had International Federation of Gynecology and Obstetrics Stage I disease, 14 Stage II, 8 Stage III and 10 Stage IV. Sixty-five patients were treated by surgery, six by radiotherapy, and four patients with advanced disease received no therapy. The surgical procedure was local excision in 17 patients, vulvectomy in 22, and radical vulvectomy with inguinal lymph node dissection in 26. Five- and 10-year corrected survival rates were 46% and 37%, respectively. Recurrences were seen in 43 (66%) of the patients treated by surgery. Independent prognostic factors for corrected survival in the entire group of 75 patients were inguinal lymph node metastases (P = 0.016), angioinvasion (P = 0.027), tumor localization to clitoris, and multifocal tumors (P = 0.043). For the 65 patients treated by surgery, independent prognostic factors for disease free survival were angioinvasion (P < 0.001), age at diagnosis (P = 0.003), DNA ploidy (P = 0.004), and ulceration (P = 0.027). The independent prognostic factors for long term survival were tumor localization to clitoris (P = 0.018), DNA ploidy (P = 0.045), and inguinal lymph node involvement (P = 0.053). Radical surgery did not improve disease free or long term survival. CONCLUSIONS: DNA ploidy is an independent factor that predicts prognosis in patients with vulvar melanoma, and should be considered together with previously known factors. Radical surgery does not improve prognosis and is not recommended when the inguinal lymph nodes are clinically negative.

Adult↗

Prognostic value of erb-B2 and myc amplification in breast cancer imprints.

BACKGROUND: Amplification of erb-B2 and myc shows prognostic value in patients with operable breast cancer. Amplification is usually detected in tumor samples remaining after pathologic work-up, preventing the examination of small tumors. METHODS: Tumor imprints that contained low numbers of contaminating normal cells were obtained from small tumors. The prognostic value of erb-B2 and myc amplification in imprint breast preparations was examined, using the polymerase chain reaction (PCR) to determine gene copy number. Tumor material was obtained from 162 patients with breast cancer operated 1975-1976. RESULTS: Amplification of erb-B2 existed in 21% and myc in 16% of the patients. Both erb-B2 and myc amplification showed prognostic significance in univariate analysis for survival and relapse free survival. In multivariate analysis, erb-B2 was a significant factor. In small tumors less than 13 mm in greatest dimension, erb-B2 showed prognostic significance for survival but not for relapse free survival. CONCLUSIONS: The use of imprints/PCR allows the detection of gene amplification in breast cancer. The procedure is suitable for the analysis of small tumors and can be used to examine very small tumors, such as those detected mammographically.

Analysis of Variance↗

Prognostic criteria in patients with stage D2 prostate cancer. Correlation with mean nuclear volume.

BACKGROUND: Histologic grading, especially the Gleason score (GS), is considered to be of value in determining the prognosis of patients with prostate cancer. However, subjective histologic grading is characterized by low reproducibility. Conversely, estimates of mean nuclear volume (MNV), developed by Gunderson and Jensen based on a stereologic technique, is a method with high reproducibility. Furthermore, it has been reported that MNV provides an accurate prognosis of bladder cancer. In this study MNV was compared with two histologic grading methods in determining the prognosis of Stage D2 prostate cancer. METHODS: A retrospective, prognostic study of 31 patients with Stage D2 prostate cancer treated with transurethral resection of the prostate or needle biopsy between January, 1983, and July, 1994, was performed. Unbiased estimates of MNV were compared with age at the time of diagnosis, histologic grading according to World Health Organization (WHO) classification, and GS on the prognostic value. RESULTS: Age at the time of diagnosis, WHO classification and GS had no value as prognostic criteria, and only MNV correlated significantly with prognosis of Stage D2 prostate cancer (P = 0.0017). CONCLUSION: Results of this study indicate that MNV is prognostically superior to morphologic grading of malignancy, such as GS and WHO classification, in Stage D2 prostate cancer.

Adenocarcinoma↗

Objective malignancy grading of squamous cell carcinoma of the lung. Stereologic estimates of mean nuclear size are of prognostic value, independent of clinical stage of disease.

BACKGROUND: The prognostic value of quantitative histopathologic parameters was evaluated in 55 consecutively treated patients with operable lung carcinoma of squamous (N = 39) and mixed, adenosquamous (N = 16) cell type. Patients alive were followed for at least 12 years. METHODS: Using a projection microscope and a simple test system in fields of vision systematically selected from the whole tumor area of one routine section, five quantitative histopathologic variables were estimated: the mean nuclear volume, the mean nuclear profile area, the density of nuclear profiles, the volume fraction of nuclei to tissue, and the number of mitotic profiles per 10(3) nuclear profiles. For each patient, information was recorded regarding sex, age at diagnosis, and clinical stage of disease. RESULTS: Single-factor analyses showed that a favorable prognosis was associated with early clinical stages (Stages I and II) and young age (P < or = 0.03), and that females tended to do better than males (P = 0.09). Estimates of the mean nuclear volume were of prognostic significance (P = 0.02), small nuclei being associated with the worst prognosis. In a multivariate Cox analysis, clinical stage, age, and mean nuclear volume were found to be parameters of significant, independent prognostic value. CONCLUSIONS: The present feasibility study indicates that estimates of the mean nuclear volume are of prognostic value, independent of the clinical stage of disease. This quantitative histopathologic variable is highly reproducible and easily obtained using an unbiased stereologic method. Thus, the mean nuclear volume may be a parameter of future importance in the clinical management of patients with carcinoma of the lung.

Aged↗

Prognostic significance of p53 and ras p21 expression in nonsmall cell lung cancer.

BACKGROUND: Alterations of the p53 gene are one of the most common genetic changes in various types of cancer, including lung cancer. Abnormalities in the ras genes, including point mutations and overexpression, are another common feature in the molecular biology of lung cancer and are associated with a poorer prognosis. The authors' purpose was to determine expression of the mutated p53 gene in nonsmall cell lung cancer (NSCLC) specimens that were studied for expression of ras p21 and to document whether altered p53 expression was also an important factor for survival. METHODS: Ninety-six patients with NSCLC underwent surgical resection between 1977 and 1985, 63 of whom received postoperative combination chemotherapy. None received radiation therapy. Tumor specimens were analyzed for altered p53 expression by immunohistochemistry. Univariate and multivariate analyses were performed to assess the association between p53 expression and survival. RESULTS: Fifty-six (58%) of 96 tumor specimens showed altered p53 expression, and 91 patients were analyzed for survival. Altered p53 expression did not correlate with clinicopathologic characteristics except for postsurgical pathologic tumor (pT) classification. The patients with altered p53 expression survived for a significantly shorter period after surgery than those without p53 expression, including all patients who underwent resection and potentially curative resection (P = 0.02 and P = 0.048, respectively, generalized Wilcoxon test). Multivariate analysis showed independent prognostic significance for altered p53 expression (hazard ratio [HR] = 1.72, P = 0.04) and surgical cure (HR = 4.69, P < 0.001). The combined analysis of mutated p53 and ras p21 expression in the same tumor specimens revealed that patients with p53- and ras p21-negative tumors survived the longest among those with different p53 and ras p21 features (P = 0.005, generalized Wilcoxon test). CONCLUSION: Altered p53 expression is a significant and independent negative prognostic factor for patients with surgically resected NSCLC: Combined immunohistochemical analysis of mutated p53 and ras p21 expression can divide patients with NSCLC into more accurate prognostic groups. If the current findings can be confirmed in larger prospective studies, combined immunohistochemical analysis of mutated p53 and ras p21 expression can be a useful clinical tool for stratifying patients with NSCLC into accurate prognostic groups and for identifying the population with a different risk of recurrence.

Aged↗

Prognostic significance of heat shock protein-27 expression in hepatocellular carcinoma and its relation to histologic grading and survival.

BACKGROUND: The expression of heat shock protein-27 (HSP-27) has been detected in some human tumors. In this study the authors investigated HSP-27 expression in patients with hepatocellular carcinoma (HCC) and examined its prognostic significance. METHODS: Expression of HSP-27 was studied in 58 HCC and adjacent noncancerous liver tissues by immunohistochemical stain. The relation between its expression and eight known prognostic factors was evaluated. RESULTS: Of the 58 HCC tissues studied, the presence of HSP-27 was demonstrated in 45 tissues (77.6%); low expression (</= 25%) was demonstrated in 17 tissues and high expression (> 25%) was demonstrated in 28 tissues. A significantly higher distribution of HSP-27 expression in HCC tissues compared with adjacent noncancerous liver tissues was obtained (P < 0.0001). Patients with high HSP-27 expression had a significantly higher histologic tumor grade than those with low HSP-27 expression (P = 0.001). The 5-year disease free survival rate of patients with high HSP-27 expression was 21.4% versus 59.3% for patients with low HSP-27 expression (P < 0.001). A similar relation was observed with overall survival (33.3% vs. 64. 8%; P = 0.009). HSP-27 expression was also identified to be a significant and powerful prognostic indicator for disease free survival (odds ratio = 2.25; P = 0.034) and for overall survival (odds ratio = 2.72; P = 0.015). CONCLUSIONS: The current study data suggest that HSP-27 expression is a powerful prognostic indicator and is related to histologic grade and survival of patients with HCC.

Adult↗

Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years.

BACKGROUND: The purposes of this study were to identify prognostic factors for response to chemotherapy, overall survival, and long term survival of patients with small cell lung carcinoma and to construct a classification of patients on the basis of their expected overall survival. METHODS: In the 763 patients registered in 4 consecutive clinical trials conducted by the European Lung Cancer Working Party from 1982 to 1993, the impact of 21 pretreatment variables assessable in a routine practice was analyzed for the various outcomes with a minimum follow-up of 5 years. RESULTS: The key prognostic role of disease extent was confirmed for all the outcomes. Additional independent prognostic factors for response to chemotherapy were gender, neutrophil count, and hemoglobin level; for overall survival, these factors were Karnofsky performance status, gender, and neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM) analysis classified patients into 4 groups, taking into consideration disease extent, Karnofsky performance status, age, gender, and neutrophil count. Median survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For long term survival, defined as a minimum survival of 2 years (9% of the patients), Karnofsky performance status was the only independent predictive factor, along with the achievement of a complete response (if this was taken into consideration). Small cell lung carcinoma remained the main cause of death among these patients. Cure was infrequent, with only 14 patients alive and disease free at 5 years (1.8%). CONCLUSIONS: In this study the long term prognosis associated with small cell lung carcinoma was poor. The well-known prognostic values of disease extent and Karnofsky performance status were confirmed, but the authors also identified age and gender (which are more controversial) as independent characteristics, in addition to citing the role of complete response in the attainment of long term survival. The independent role of neutrophils observed by the authors. must be validated by further studies.

Adult↗

The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma.

BACKGROUND: The prognostic significance and nature of p53 dysfunction in ovarian carcinoma is unclear. The relation between p53 overexpression, p53 mutations, and their effects on overall survival in primary ovarian carcinoma is explored. METHODS: Tumor specimens from 171 consecutive epithelial ovarian carcinomas were examined for overexpression of p53 protein with DO7 antibody. P53 mutations were determined by direct sequencing. The influences of conventional histopathologic prognostic factors and various p53 molecular alterations on overall survival were assessed. RESULTS: Overall, 48.5% and 57.3% of the samples showed p53 overexpression and p53 mutation, respectively. Although neither p53 overexpression nor the mere presence of a p53 mutation impacted overall survival, the combination did prognosticate survival both in univariate and multivariate models. The authors' results suggest 4 mechanisms that may affect p53 dysfunction in nearly 100% of advanced stage ovarian carcinomas. These include null mutation, nonresponsive p53 (wild-type [wt] p53 sequence, DO7 negative), sequestration (wt p53 sequence, DO7 positive), and missense mutation. Median survival for these groups that constitute sequentially 21.3%, 20.5%, 12.3%, and 45.9% of the 122 Stage III or IV (International Federation of Gynecology and Obstetrics) cancers was 1.49, 1.31, 3.09, and 3.6 years, respectively. The nonresponsive p53 and null sequence tumors grouped together as functionally null convey the worst prognosis relative to missense mutations in a univariate model (P = 0.006). Functionally null p53 (P = 0.002), stage (P = 0.008), and optimal cytoreduction (P = 0.008) were independent prognostic factors by multivariate analysis. CONCLUSIONS: Sequestration of wt p53 is unique to advanced stage ovarian carcinoma. Functionally null p53 represents an independent molecular predictor of compromised survival.

Adult↗

Increased expression of laminin-5 and its prognostic significance in lung adenocarcinomas of small size. An immunohistochemical analysis of 102 cases.

BACKGROUND: Laminin-5 plays an important role in cell migration during tissue remodeling and tumor invasion. METHODS: The authors studied the expression of laminin-5 immunohistochemically in 102 cases of small-sized lung adenocarcinoma (maximum dimension < or = 2 cm) using a monoclonal antibody against the laminin gamma2 chain, and they also investigated the associations of laminin-5 with clinicopathologic characteristics. Prognostic significance of increased laminin-5 expression was evaluated using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: Overall, laminin-5 expression was observed in 82 cases (80.4%): 7 of 18 (38.9%) bronchioloalveolar carcinomas and 75 of 84 (89.3%) invasive adenocarcinomas. Laminin-5 was preferentially localized in the cytoplasm of tumor cells at the tumor-stromal interface, where budding or dissociation of cancer cells was frequently observed. Overexpression of laminin-5 (24 cases, 23.5%) was associated with vascular invasion (P = 0.021) and stromal fibroblastic reaction (P = 0.005) but not with nodal involvement, lymphatic invasion, or pleural invasion. Survival analysis revealed that overexpression of laminin-5 was associated with shorter patient survival (P = 0.0027 by log rank test). On multivariate analysis, overexpression of laminin-5 was an independent prognostic factor (P = 0.030), as were nodal involvement (P < 0.0001), vascular invasion (P = 0.047), and lymphatic invasion (P = 0.0047) in a whole cohort of patients. Moreover, when patients with Stage I (International Union Against Cancer [UICC] staging system) disease were considered in multivariate analysis, overexpression of laminin-5 was the only significant prognostic factor (P = 0.022), whereas vascular invasion had a marginally significant impact (P = 0.07) on patient survival. CONCLUSIONS: The authors' results showed that laminin-5 is frequently expressed by cancer cells at the invasive front of lung adenocarcinoma. The study concluded that overexpression of laminin-5 may be a useful prognostic factor in patients with small-sized lung adenocarcinoma, especially in Stage I cases.

Adenocarcinoma↗

Comparison of prognostic models in patients with advanced Hodgkin disease. Promising results from integration of the best three systems.

BACKGROUND: Several prognostic systems have been elaborated for patients with Hodgkin disease (HD) over the last 12 years, but early identification of a reasonably large group of both low and high risk, advanced stage patients remains unsatisfactory. METHODS: Seven well known models were applied to 516 patients with advanced HD, with 315 patients used for the study sample and 201 patients used for the test sample. Individual performances as well as joint performances were analyzed univariately and multivariately in relation to overall survival, recurrence free survival, and time to treatment failure by means of a proportional hazards model. RESULTS: None of the models identified a group containing > 10% of patients from the total population who had a failure risk of either < or = 10% or > or = 50%. The systems of the International Database on Hodgkin Disease, the Memorial Sloan-Kettering Cancer Center, and the International Prognostic Factor Project showed the best prognostic power; only these three, when analyzed together, predicted clinical outcome with a statistically significant fit to the clinical data. Integration of the three systems in a linear model dramatically improved their individual discriminatory capacity by identifying patients with 10% and 50% failure risks, respectively, in 23% and 24% of the study patient population and in 19% and 25% of the test population, respectively. CONCLUSIONS: As powerful and simple new prognostic factors are awaited that may improve our predictive ability, this integrated index is probably the best way to exploit the significance of those presently available. The program required for the calculations can be downloaded from the Internet at the web site http://www.unimo.it/gisl/default.htm.

Adolescent↗

Hyaluronan content in pleural fluid as a prognostic factor in patients with malignant pleural mesothelioma.

BACKGROUND: Regardless of the modality of therapy used, malignant pleural mesothelioma is a highly treatment-resistant and invariably fatal disease. Identification of prognostic variables are important for future investigational therapeutic studies. METHODS: The prognostic significance of various clinical variables, including hyaluronan levels in pleural fluid, was evaluated in a retrospective analysis in 100 patients with histologically confirmed malignant pleural mesothelioma. RESULTS: The overall median survival was 11.5 months. Univariate analyses identified histologic subtype, i.e., epithelial or mixed, and elevated content of hyaluronan in the pleural effusion as significant prognostic variables. A multivariate analysis confirmed the independent predictive power of histologic subtype, and an elevated concentration of hyaluronan in the pleural fluid also indicated longer survival in older patients and in patients receiving therapy other than supportive. CONCLUSIONS: The prognostic value of histologic subtype and the concentration of hyaluronan in pleural effusions should be considered when designing and evaluating treatment trials for patients with malignant pleural mesothelioma.

Adult↗

Lymphatic vessel invasion is an independent prognostic factor in patients with a primary resected tumor with esophageal squamous cell carcinoma.

BACKGROUND: Little data exist about the prognostic role of a lymphatic vessel invasion (LVI) in patients with esophageal carcinoma. The objective of this study was to clarify the presence and prognostic impact of LVI in a large group of patients resected for esophageal squamous cell carcinoma (SCC) at one surgical center. METHODS: Three hundred sixty-six patients, who had a primary resection for SCC, were analyzed by univariate and multivariate analysis. Follow-up was complete for 93.7% patients with a median follow-up of 8.3 years. RESULTS: The total rate of LVI was 39.1% (n = 143). Univariate analysis revealed a significant relation between LVI and different T classifications (P = 0.001), N classifications (P < 0.0001), M classifications (P < 0.0001), International Union Against Cancer (UICC) stages (P < 0.0001), and residual tumor (P < 0.0001). Multivariate analysis of the patients with R0-resected tumors proved LVI as an independent prognostic factor. The 2-, 5- and 10-year survival rates in patients with LVI were 28.5%, 11.1%, and 9.2% compared with 63.4%, 46.6%, and 27%, respectively, without LVI (P < 0.0001). Patients with LVI had a median survival time of 11.4 months compared with 28.6 months without LVI (P < 0.0001). Patients with R0-resected tumors without LVI had a median survival time of 54.1 months compared with 12.1 months in patients with LVI (P < 0.0001) and compared with 11.3 months in patients with R1-resected tumors P < 0.0001). CONCLUSIONS: These data clearly show that LVI is an independent prognostic factor in patients with SCC and confirm the importance of a systematic pathohistologic workup. The prognosis of patients with R0-resected tumors with LVI is equal to patients with an incomplete tumor resection. This supports the inclusion of LVI in the UICC classification system for esophageal carcinoma.

Adult↗

Immune function, telomerase, and angiogenesis in patients with primary, operable nonsmall cell lung carcinoma: tumor size and lymph node status remain the most important prognostic features.

BACKGROUND: Lung carcinoma usually is advanced at the time of presentation and frequently shows metastatic spread. In recent times, prognostic factors such as c-erbB-2 in patients with breast carcinoma have provided useful information and beneficial therapeutic targets. The objective of this study was to evaluate angiogenesis, immune function, and telomerase expression in patients with nonsmall cell lung carcinoma (NSCLC) to determine their prognostic significance. METHODS: Immunohistochemistry was used to evaluate the expression of human telomerase reverse transcriptase (hTERT; n = 115 patients), interleukin-2r (IL-2r; n = 40 patients), microvessel density (MVD; n = 81 patients), and vascular endothelial growth factor (VEGF; n = 61 patients). Three-year survival follow-up information was available for most patients, and a comprehensive review of clinicopathologic features was carried out. RESULTS: Fifty percent of tumors showed nuclear staining for hTERT, 55% of tumors showed some degree of lymphocyte IL-2r expression, 33% of tumors were recorded with an MVD that was higher than average, and VEGF staining was detected in 85% of tumors. None of the parameters measured had an impact on survival. hTERT expression was correlated with lymph node status. Lymph node status and tumor size were identified as independent prognostic factors. CONCLUSIONS: This study failed to identify a marker of prognosis for patients with NSCLC other than tumor size and lymph node status in this population. Telomerase expression was associated with metastases, raising the possibility that this enzyme is involved in the metastatic process. Tumor cell VEGF expression was identified frequently: This growth factor may have potential as a target for antiangiogenic therapy. Lung carcinoma typically is the result of large numbers of mutations. Further understanding of the biologic implications of these mutations will lead to the development of effective prognostic markers and treatments for patients with NSCLC.

Adult↗