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PubMed2006

High positive sentinel node identification rate by EORTC melanoma group protocol. Prognostic indicators of metastatic patterns after sentinel node biopsy in melanoma.

Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS. The positive SN-identification rate was 29% at a median Breslow thickness of 2.00 mm and the false-negative rate was 9.4%. Breslow thickness and ulceration of the primary correlated with SN status. SN status, ulceration and site of the primary tumour correlated with DFS. SN status and ulceration of the primary correlated with OS. The in-transit metastasis rate correlated with SN-positivity, Breslow thickness and ulceration. Projected 3-year OS was 95% in SN-negative and 74% in SN-positive patients. Transhilar bivalving of the SN with step sections from the central planes is simple and had a high SN-positive detection rate of about 30%. The SN status is the most important predictive value for DFS and OS. In-transit metastasis rates correlated with SN-positivity, Breslow thickness and ulceration of the primary.

Adolescent↗
PubMed1998

Is prostate specific antigen density an important prognostic indicator for patients with prostate cancer treated with external beam therapy?

The purpose of this study was to determine if prostate specific antigen density (PSAD) is a predictor of outcome following external beam radiotherapy for prostate cancer, and to compare it with other prognostic factors. Between January 1990 and December 1993, 205 patients with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation, with no prior or adjuvant hormonal therapy. All patients had pre- and post-treatment serum prostate specific antigen (PSA) evaluation. They were followed up for at least 24 months. PSAD was defined as the ratio of pre-treatment serum PSA to the prostate volume, as determined from CT treatment planning scans. Prostate volumes were calculated using the prostate ellipse formula. Median PSA density was 0.37, with a range 0.01-6.7. Biochemical failure was defined as three consecutive rises in serum PSA, regardless of the magnitude of elevation. 4-year biochemical disease-free survival (BDFS) for patients with PSAD < or = 0.3 was 60%, compared with 22% for patients with PSAD > 0.3 (p = < 0.001). In a multivariate analysis, pre-treatment PSA (p = < 0.001), Gleason score (p = 0.002), and stage (p = 0.03) were independent predictors of BDFS, while PSAD was not an important prognosticator (p = 0.62). Pre-treatment serum PSA is the most important prognosticator of BDFS, following external beam radiotherapy, for patients with prostate cancer. PSA density did not predict treatment outcome.

Adenocarcinoma↗
PubMed2000

Acquired expression of p27 is a favorable prognostic indicator in patients with hepatocellular carcinoma.

The p27 cyclin-dependent kinase inhibitor is a negative regulator of cell-cycle progression. In many human epithelial malignancies, decreased expression of p27 correlates with high grade, early recurrence, and poor prognosis. To evaluate the prognostic significance of p27 in hepatocellular carcinoma (HCC), we studied 54 HCCs along with corresponding nontumoral tissue. Immunohistochemistry (IHC) and Western blot (WB) analysis before and after immunoprecipitation with Cdk2 were performed on paraffin-embedded tissues and protein homogenates, respectively, to compare localization and expression of the p27 protein and to determine the total and active (Cdk2-bound) fractions of p27. Correlations were analyzed between IHC-assessed levels of p27, survival, and major clinical and pathological variables. IHC revealed no p27 expression in the majority of hepatocytes from normal and cirrhotic liver, whereas 14 HCCs (26%) were high p27 expressers (>50% positive cells), 26 (48%) low expressers (<50% positive cells), and 14 (26%) negative. High IHC signals of p27 correlated with Cdk2-bound p27 as assessed by immunoprecipitation-WB; by contrast, WB alone displayed similar levels of p27 protein in all normal and tumoral samples. High IHC p27 expression correlated with prolonged survival (P = 0.027), whereas the presence of cirrhosis was associated with poor outcome (P = 0.029). We conclude that with respect to their nonneoplastic counterparts, a subset of HCCs acquire significant p27 expression and that high expression of p27 is a favorable independent prognostic parameter for HCC.

Aged↗
PubMed1993

A comparison of flow cytometric and absorption cytometric DNA values as prognostic indicators for pancreatic carcinoma.

BACKGROUND: The DNA content of 30 adenocarcinomas of the head of the pancreas was measured by flow and absorption cytometric analysis. METHODS: Each of the patients in this study had curative pancreatoduodenectomy. The absorption cytometric measurements were done in a research laboratory, and the flow cytometric measurements were performed in a commercial laboratory. The DNA measurements were done on nuclei disaggregated from pancreatic cancer tissue blocks without the examiner knowing whether the patient had survived. RESULTS: Twenty-one of the 30 cancers were found to be aneuploid by absorption cytometric analysis, whereas only 1 of the 30 cancers was aneuploid by flow cytometric analysis. This difference was statistically significant (P < 0.001). CONCLUSIONS: Univariate and multivariate analyses showed that the absorption cytometric DNA measurements were stronger prognostic determinants for patient survival than were the flow cytometric DNA measurements, indicating that some caution may be warranted in the interpretation of commercially obtained DNA distributions of pancreatic carcinomas.

Analysis of Variance↗
PubMed2006

Progesterone and estrogen receptors: opposing prognostic indicators in meningiomas.

OBJECT: The preponderance of progesterone receptors (PRs) and the scarcity of estrogen receptors (ERs) in meningiomas are well known. The expression of PRs may relate to tumor grade and recurrence. Cytogenetic abnormalities are associated with aggressive behavior, recurrence, and progression. In this study, the authors focus on the prognostic implications of hormone receptors in meningiomas to help determine the clinical and biological aggressiveness of tumors and their correlations with cytogenetic abnormalities. METHODS: Two hundred thirty-nine patients with meningiomas were separated into three groups. Group 1 (PR-positive group) comprised patients whose meningiomas displayed expression of PRs alone. Group 2 (receptor-negative group) included patients whose lesions did not have receptors for either progesterone or estrogen. Group 3 (ER-positive group) included patients whose tumors displayed expression of ERs. Clinical and histological findings, proliferative indices, tumor recurrence, and cytogenetic findings were analyzed by performing the Fisher exact test. Compared with the receptor-negative (Group 2) and ER-positive (Group 3) groups, the PR-positive group (Group 1) had a statistically significant lower proliferative index and a smaller number of patients in whom there were aggressive histopathological findings or changes in karyotype. In Groups 1, 2, and 3, the percentages of cases with aggressive histopathological findings were 10, 31, and 33%, respectively; the percentages of cases with chromosomal abnormalities were 50, 84, and 86%, respectively; and the percentages of cases in which there initially was no residual tumor but recurrence was documented were 5, 30, and 27%, respectively. A statistically significant increase in the involvement of chromosomes 14 and 22 was identified in receptor-negative and ER-positive de novo meningiomas, when compared with the PR-positive group. Abnormalities on chromosome 19 were statistically significantly higher in receptor-negative meningiomas than in PR-positive tumors. CONCLUSIONS: The expression of the PR alone in meningiomas signals a favorable clinical and biological outcome. A lack of receptors or the presence of ERs in meningiomas correlates with an accumulation of qualitative and quantitative karyotype abnormalities, a higher proportional involvement of chromosomes 14 and 22 in de novo tumors, and an increasing potential for aggressive clinical behavior, progression, and recurrence of these lesions. Sex hormone receptor status should routinely be studied for its prognostic value, especially in female patients, and should be taken into account in tumor grading. The initial receptor status of a tumor may change in progression or recurrence of tumor.

Adult↗
PubMed1982

Prognostic indicators in stage III and localized stage IV breast cancer.

One hundred eighty-three patients with Stage III and nonmetastatic Stage IV breast cancer, seen between 1960-1975 at the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, were retrospectively analyzed to determine the prognostic significance of the following clinical features: (1) "grave signs" (skin ulceration, skin fixation, chest wall fixation, and edema); (2) size of primary tumor; (3) nodal stage; and (4) inflammatory changes. Since therapy among 147 patients with noninflammatory cancer comprised of either irradiation alone (54 patients) or surgery plus irradiation (93 patients), all the above factors were analyzed also with respect to the method of treatment. In 147 patients with noninflammatory carcinoma, the local failure rate, regional failure rate, distant failure rate and five-year disease free survival were all unaffected by the presence or absence of "grave signs," whether treated by irradiation alone or surgery plus irradiation. The size of the primary tumor, in patients treated with irradiation alone, influenced the rate of local failure (44% for tumors 0-8 cm and 76% for tumors greater than or equal to 8 cm) and five-year disease-free survival (30 versus 4%, respectively). Such a statistically significant difference in local failure rate or disease-free survival was not noted when treated with combined modality. N stage also influenced the prognosis in patients treated with irradiation alone since the regional failure rate increased from 9% for N0, N1 to 58% for N2, N3 patients. This was reflected in a decreased disease-free survival (4 versus 30%) for patients with advanced nodal disease who were treated with irradiation alone. No such difference was noted when the nodal disease was treated with a combination of surgery and irradiation. The 36 patients with inflammatory carcinoma had essentially the same incidence of local, regional and distant failure as the 147 patients with noninflammatory carcinoma but the appearance of distant metastases occurred significantly earlier in patients with inflammatory carcinoma than in those with noninflammatory carcinoma. This earlier appearance of distant metastases was reflected in the significantly lower disease-free survival for the patients with inflammatory carcinoma (6 versus 28%). The data from this analysis suggests that consideration should be given to removing the presence of grave signs from the current AJC staging system and substituting in its place the size of the primary tumor (less than 8 cm versus greater than or equal to 8 cm). Further analysis on a large number of patients is needed to substantitate this recommendation.

Breast Neoplasms↗
PubMed1992

Flow cytometric analysis of uterine sarcoma: ploidy and S-phase rate as prognostic indicators.

Flow cytometry of various gynecological tumors has shown that aneuploid tumors and a high S-phase rate carry a prognosis worse than that of diploid tumors or tumors with a low S-phase. The aim of this study is to investigate the prognostic importance of DNA ploidy and S-phase rate in relation to mitotic count, tumor stage, tumor grade, and histology in 37 patients with uterine sarcoma stages I-IV (FIGO). Flow cytometry was performed on archival paraffin-embedded tumor tissue and the histologic specimens were reviewed by a single pathologist. Nineteen (51%) of the tumors were classified as DNA aneuploid. The S-phase fraction (SPF) was determined in 33 cases. The mean SPF (+/- SD) was 15.0% (+/- 9.5%). The mean SPF was three times higher in aneuploid tumors than in diploid cases. Both the proportion of aneuploid tumors and the mean SPF were significantly higher in later stage tumors, more poorly differentiated tumors, and tumors with a higher mitotic index. No significant differences were seen between histologic types with respect to the two cytometric variables. The 5-year cancer survival rate was only 11% in aneuploid cases compared with 59% in diploid cases (log rank, P = 0.0002). There was a significantly worse prognosis in cases with a higher SPF (P = 0.0009) and in case with a higher mitotic index (P = 0.0016). In the multivariate survival analysis using the Cox proportional hazards model, DNA ploidy showed a significant prognostic value (P = 0.046) even when adjusted for stage, grade, and mitotic index. When adjusted for stage and grade only, SPF showed significant additional prognostic value.

Adult↗
PubMed1997

Proliferating cell nuclear antigen and MIB-1. An alternative to classic prognostic indicators in renal cell carcinomas?

Tumor progression and clinical outcome for patients with renal cell carcinomas (RCCs) cannot be predicted based solely on tumor staging and grading. In a retrospective study we have therefore attempted to analyze the capacity of proliferation markers to provide additional prognostic information. One hundred seven cases of RCC were investigated by immunohistochemical analysis using two different monoclonal antibodies: PC10, which recognizes a proliferating cell nuclear antigen (PCNA), and MIB-1, which identifies the Ki-67 antigen in formalin-fixed, paraffin-embedded material. PCNA frequency ranged from 0% to 71% (mean, 17%), and MIB-1 expression, from 0% to 43% (mean, 11%). PCNA scores correlated significantly with MIB-1 immunoreactivity. PCNA and MIB-1 immunoreactivity showed a significant correlation with tumor grade. A strong correlation was also observed for T-component of stage and MIB-1 scores, but no correlation was found between PCNA and T-component of stage. In univariate analysis, PCNA immunoreactivity and MIB-1 scores were significant predictors of survival. Multivariate analysis, using a Cox proportional hazard model, showed PCNA index, N-component of stage, and tumor grade to be independent predictors of tumor progression, which is not the case for MIB-1 index.

Adult↗
PubMed2005

Multidrug resistance as a potential prognostic indicator in acute myeloid leukemia with normal karyotypes.

INTRODUCTION: Approximately 45% of adults with acute myeloid leukemia (AML) have normal karyotypes and therefore lack structural abnormalities that can assist in the localization and characterization of molecular defects. The current study attempted to evaluate the potential prognostic role of multidrug resistance (MDR), regarded as one of the potential prognostic factors for the outcome of overall AML, for AML with normal karyotypes. METHOD AND MATERIALS: A functional MDR assay was performed in pretreatment samples from AML patients with normal karyotypes. The complete remission (CR) rate, event-free survival (EFS), and overall survival (OS) were analyzed according to the MDR status and clinical prognostic factors for 88 patients with AML with normal karyotypes. RESULTS: MDR by efflux was expressed in 14 out of 48 evaluable patients (29%) but failed to identify the association with CR (p = 0.124). However, MDR was identified as an independent prognostic factor for EFS and OS (p = 0.013 and 0.046) together with the use of stem cell transplantation (p = 0.009 for EFS and 0.029 for OS) and the WBC count at presentation (p = 0.023 for EFS and 0.034 for OS). CONCLUSION: The functional MDR assay may provide information on the prognosis of AML patients with normal karyotypes, and it might be a possible guideline for risk-stratified treatment strategies in AML with normal karyotypes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Malignant paraganglioma of the urinary bladder: Immunohistochemical study of prognostic indicators.

Using various immunohistochemical markers, the objective of our study was to assess whether correlation exists between growth potential of paraganglioma (pheochromocytoma) cells and formation of metastasis. The patient was a 28-yr-old man who presented with intermittent episodes of gross hematuria due to a mass in the urinary bladder. He had no constitutional symptoms to suggest paraganglioma. Histologic, immunohistochemical, and electron microscopic investigation of the surgically removed tissue proved that the tumor was a malignant paraganglioma with metastases in the regional lymph nodes. The immunohistochemical tests were not supportive of high cell proliferation index, indicating that metastases can develop in the absence of rapid multiplication of the tumor cells. Abnormalities in vascular architecture and marked expression of VEGF in the tumor cells may be regarded as prognostic signs to predict the formation of metastases.

Adult↗
PubMed1995

Expression of the p53 protein in malignant melanomas as a prognostic indicator.

It is currently widely accepted that the tumour suppressor gene p53 is critically involved in the proliferation and differentiation of tumour cells including melanoma cells. In the present study, we examined 60 cases of primary melanoma to compare the expression of p53 protein with conventional prognostic markers for melanoma such as clinical and histological parameters. No correlation was found between the p53 protein and clinical factors except for the presence of a metastatic node and development to clinical stage II. However, the expression of p53 protein was significantly associated with tumour thickness over 1.5 mm, levels IV and V of invasion, the presence of ulceration, and high mitotic rate for 5-year survival rate. Although many questions still remain to be answered, our results and those of others for various other malignant tumours, implicate p53 in malignant transformation of pigment cells. Indeed, it could be a new marker for an unfavourable prognosis of malignant melanoma, even though the gene mutation in this highly lethal tumour has yet to be established.

Adult↗
PubMed1997

Histopathology and pathologic prognostic indicators.

Conventional squamous cell carcinoma is the most common type of laryngeal cancer. Nevertheless, it is important to be cognizant of the less common laryngeal malignancies because of their distinctive clinical behavior and the concomitant implications for therapy. Additionally, it would be useful to identify pathologic prognostic factors in laryngeal squamous cell carcinoma that would allow optimal individualization of therapy. The histopathology of various laryngeal malignancies and various putative pathologic prognosticators in laryngeal squamous cell carcinoma are reviewed.

Carcinoma, Neuroendocrine↗
PubMed1984

Toxic epidermal necrolysis. Granulocytic leukopenia as a prognostic indicator.

Drug-induced toxic epidermal necrolysis is a disease of severe morbidity and high mortality. In the ten cases reported herein, therapeutic measures, including antibiotics, closed mechanical ventilation, maintenance of fluid and electrolyte balance, and management in special burn-care units, failed to alter a poor prognosis. The administration of corticosteroids was of no apparent benefit and may have been detrimental. Young age seemed to have a favorable influence on survival. There developed a pattern of leukopenia due to severe granulocytopenia that proved to be of prognostic importance. Persistence of the granulocytopenia portended a fatal outcome, whereas recovery of the granulocyte count to normal indicated, overall, a more favorable trend. The cause of the granulocytopenia could not be determined.

Adolescent↗
PubMed1996

Preoperative CYFRA 21-1 level as a prognostic indicator in resected primary squamous cell lung cancer.

The CYFRA 21-1 assay is a test that has been developed recently for detection of a cytokeratin 19 fragment in serum. A diagnostic role for CYFRA 21-1 has already been proposed. The question of whether this marker is prognostically significant is important in clarifying the role of CYFRA 21-1 in clinical practice. The aim of this study was to evaluate the prognostic significance of elevated preoperative CYFRA 21-1 levels in patients with resected primary squamous-cell lung cancer (SqCC). Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 91 patients with operable SqCC. Survival and disease-free survival curves related to initial levels of this marker were estimated using the Kaplan-Meier method. In the univariate analysis the log-rank test and the log-rank test for trend were used. In the multivariate analysis the stratified log-rank test and the proportional hazard model were used. Elevated preoperative CYFRA 21-1 levels were identified in 55% of patients with SqCC. The number of patients with elevated levels of this marker increased with TNM stage (P = 0.0001). In univariate analysis elevated levels of CYFRA 21-1 were significantly associated with poor overall survival (P < 0.00005) and with disease-free survival (P < 0.00005). In multivariate analysis elevated levels of this marker were also found to be associated with poor overall and disease-free survival (P = 0.01 and P = 0.003 respectively). In conclusion, CYFRA 21-1 may be an independent prognostic parameter of survival and tumour relapse in SqCC and may be useful in identifying resected SqCC patients at high risk of treatment failure.

Adult↗
PubMed2002

Serum tissue polypeptide specific antigen as a noninvasive prognostic indicator for early recurrence of hepatocellular carcinoma after curative resection.

BACKGROUND: Serum tissue polypeptide specific antigen (TPS) is a useful cell proliferation marker in diagnosing and monitoring patients with a variety of malignancies. The objective of this study was to determine the usefulness of serum TPS as a noninvasive prognostic factor for early recurrence of hepatocellular carcinoma (HCC) after patients undergo curative resection. METHODS: Serum TPS levels were measured by monoclonal TPS immunoradiometric assay in 54 patients shortly before they underwent curative resection for HCC. The recurrence time was correlated with the TPS level and with other prognostic factors using the log-rank test in univariate analysis and a Cox regression in multivariate analysis. Receiver operating characteristic analysis was performed to examine the power of the various prognostic factors to distinguish between patients with recurrent tumors and patients who were disease free. RESULTS: Patients who had higher levels of TPS (>or= 150 U/L) had earlier recurrences compared with patients who had lower levels of TPS (< 150 U/L; P = 0.016) in univariate analysis. Tumor size, the number of tumors, portal vein invasion, and the resection margins also were associated significantly with the time to tumor recurrence (P = 0.015, P = 0.004, P = 0.003, and P = 0.003, respectively). Serum alpha-fetoprotein was not a significant risk factor for tumor recurrence. In multivariate analysis, the TPS level, tumor size, and resection margins were independent prognostic factors (P = 0.025, P = 0.018, and P = 0.016, respectively). The inclusion of TPS in addition to tumor size and resection margins increased the rate of corrective prediction from 0.72 to 0.80. CONCLUSIONS: The current study demonstrated that the preoperative serum TPS level was a significant factor in predicting early recurrence of HCC after curative resection. Patients with high serum TPS levels warrant more aggressive treatment and close follow-up after they undergo tumor resection.

Adult↗
PubMed2001

PAS-positive loops and networks as a prognostic indicator in cutaneous malignant melanoma.

Recently, microvascular channels, as detected by PAS histochemistry, were positively correlated with poor prognosis in uveal malignant melanoma. Since uveal melanomas are not penetrated by lymphatic vessels, while cutaneous melanomas are, the question arises as to whether these loops and networks are also of prognostic relevance in cutaneous melanoma. Histochemically and immunohistochemically detected loops and networks in 100 cases of cutaneous malignant melanoma were correlated with the occurrence of metastasis in a 10-year follow-up study. To detect these patterns, the significance of various methods (PAS reaction with/without nuclear counterstain, anti-laminin immunohistochemistry) was investigated. The presence of loops and networks was a highly significant prognostic marker (p<0.0001) for metastasis in cutaneous malignant melanoma. The presence of these patterns proved to have higher prognostic relevance for metastasis than Breslow's tumour thickness, especially for stage IB and stage IIA tumours (intermediate thickness/risk). PAS reaction without nuclear counterstain proved to be the best method to detect these patterns. Compared with the conventional staging of Breslow's tumour thickness, and especially so for stage IB and IIA melanomas, the determination of PAS-positive loops and networks in cutaneous malignant melanoma provides additional prognostic information.

Adult↗
PubMed1998

Ratio of CD44 epithelial variant to CD44 hematopoietic variant is a useful prognostic indicator in gastric and colorectal carcinoma.

BACKGROUND: The CD44 is a cell adhesion molecule that is present as numerous isoforms created by mRNA alternative splicing. Expression of variant isoforms of CD44 is associated with tumor growth and metastasis. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in gastric and colorectal cancer. METHODS: We performed a polymerase chain reaction analysis following reverse transcriptase treatment for CD44 expression in fresh surgical specimens obtained from 25 colon carcinomas and 30 gastric carcinomas and matched adjacent normal mucosa. We determined the epithelial variant/hematopoietic variant (E/H) ratio (the amount of the CD44 epithelial variant transcript relative to the CD44 hematopoietic variant transcript) in cancer tissues and examined it for correlations with clinicopathological parameters and survival rate. RESULTS: The E/H ratio in tumor tissue was significantly higher than that in adjacent non-cancerous mucosa. In gastric and colorectal cancer tissues, there was no significant relationship between E/H ratio and clinicopathological parameters. However, patients who died due to tumor recurrence had a higher E/H ratio than surviving patients with colorectal cancer. In gastric cancer, patients with high E/H tumors had a shorter survival time than those with low E/H tumors. CONCLUSIONS: Our results suggest that the E/H ratio is a useful indicator of prognosis in gastric and colorectal carcinoma.

Adult↗
PubMed1996

[Value of immunohistochemical determination of receptors, tissue proteases, tumor suppressor proteins and proliferation markers as prognostic indicators in primary breast carcinoma].

OBJECTIVE: We tested whether immunohistochemical detection of oestrogen and progesterone receptor (ER, PR), the oestrogen-dependent protein pS2, the growth hormone receptors p 185neu and EGF-R, the tumour suppressor protein p53, the tissue proteases Cathepsin D and Urokinase, and the proliferation marker PCNA are of prognostic relevance in breast cancer patients. METHODS: Expression of the proteins listed above was evaluated in formalin-fixed and paraffin-embedded sections of 311 primary breast cancer specimens using modified Avidin-Biotin-Complex methods. Results were correlated to clinical and morphological parameters (age, menopausal status, nodal status, tumour size, tumour grade), and clinical course of disease (complete follow-up in 301 women, median observation time 62 months) utilising univariate and multivariate statistical analyses. RESULTS: If univariate analyses and multivariate regression analyses according to the Cox-model were applied, only Cathepsin D correlated to an elevated risk for recurrence in nodally negative patients (n = 135). In nodally positive women (n = 161), increasing tumour size, tumour grade, lack of ER and PR, expression of p185neu, p53, and PCNA indicated a significantly increased relative risk. CONCLUSIONS: Immunohistochemistry allows the detection of parameters which may indicate prognosis in subgroup of breast cancer patients.

Adult↗