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Interobserver variability associated with the MIB-1 labeling index: high levels suggest limited prognostic usefulness for patients with primary brain tumors.

BACKGROUND: The use of the MIB-1 labeling index (LI) as a potential prognostic marker for patients with primary brain tumors is controversial. Many studies advocating its prognostic usefulness have suggested discrete MIB-1 LI cut-off values, above which patients have significantly worse outcomes. However, interobserver variability associated previously with MIB-1 LI calculation has not been reported despite the fact that the degree of interobserver variability impacts the clinical usefulness of such cut-off values. METHODS: MIB-1 LIs were calculated independently using a standardized protocol by six pathologist observers for 50 astrocytic gliomas of varying grades. The level of interobserver agreement was determined by calculating kappa statistics for pairwise pathologist comparisons using MIB-1 LI cut-off values of 2.5%, 5.0%, 8.0%, 11.0%, and 15.0%. Spearman rank correlation coefficients were used to assess the pairwise associations between observer MIB-1 LIs. RESULTS: Although there was general agreement among pathologists regarding whether an MIB-1 LI for a given astroglial tumor was low, moderate, or high based on the analysis of correlation, a high level of interobserver variability was associated with the determination of specific MIB-1 LIs. The highest level of agreement occurred using a cut-off value of 5.0%, with pairwise kappa statistics for this value ranging from 0.52 to 0.80. CONCLUSIONS: The high level of interobserver variability suggests that proposed discrete MIB-1 LI prognostic cut-off values most likely are not useful clinically for predicting outcome for individual patients with primary brain tumors. Further prospective studies are needed investigating the prognostic usefulness of MIB-1 LI ranges that optimize interobserver agreement.

Antigens, Nuclear↗

Prognostic relevance of serum levels of the angiogenic peptide bFGF in advanced carcinoma of the head and neck treated by primary radiochemotherapy.

BACKGROUND: The objective of this trial was to analyze the prognostic relevance of the angiogenic peptides basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) in the serum of patients with advanced carcinoma of the head and neck treated by primary radiochemotherapy. METHODS: From 1992 to 1995, 26 patients with advanced head and neck cancer (25 stage IV, 1 stage III UICC) were treated according to the protocol of radiochemotherapy with carboplatin. The pretreatment serum levels VEGF, bFGF, and MMP-2 were measured by ELISA, and data were correlated with tumor characteristics and followed up (median time of follow up, 60 months). RESULTS: An increase in bFGF serum level above the upper limit of normal controls showed a significant correlation with shorter time the of locoregional control (p =.036). In covariant analysis bFGF serum concentration proved to be independent of other prognostic factors like tumor site, age, total tumor volume, and response to therapy. No prognostic relevance of VEGF and MMP-2 serum levels could be determined. CONCLUSIONS: The results of this pilot study indicate that the serum concentration of bFGF has prognostic relevance for advanced head and neck cancer.

Adult↗

Peripheral neuropathy with necrotizing vasculitis in rheumatoid arthritis. A clinicopathologic and prognostic study of thirty-two patients.

OBJECTIVE: To examine the clinicopathologic features of the noncompressive neuropathies in rheumatoid arthritis (RA). METHODS: We studied 32 patients with RA and peripheral neuropathy whose nerve and/or muscle biopsy specimens exhibited necrotizing vasculitis. Morphologic analysis of nerve specimens included light and electron microscopy studies and teased fiber preparation. Survival was evaluated, and the prognostic values of clinical, biologic, and pathologic features were assessed by Cox proportional hazards model. A prognostic assessment based on the significant variables was devised to estimate the probability of survival of any individual patient. RESULTS: Epi- and/or perineurial vasculitis was observed with the same frequency in the 17 patients with sensory and motor deficit and the 15 patients with sensory neuropathies and was associated with axonal degeneration of an average of 77.7% of the nerve fibers. The mean followup was 7.2 years, and the overall survival rate at 5 years was 57%. A full prolonged remission of the vasculitis was observed in 53% of the patients; relapse occurred in 25%. The factors correlated with mortality, in decreasing order of significance, were clinical cutaneous vasculitis (P = 0.0003), neuropathy affecting 3 or 4 limbs (P = 0.03), and depressed level of C4 (P < 0.05). The prognostic assessment indicated a wide range of 5-year probabilities of survival, from < 1% to 93%. CONCLUSION: Necrotizing vasculitis is responsible for the different patterns of noncompressive neuropathies in RA, including mononeuritis multiplex and distal symmetric sensory or sensorimotor neuropathy. Cutaneous vasculitis, multifocal neuropathy, and depressed C4 level were the 3 independent variables which best predicted mortality. We propose a prognostic assessment according to these variables, to stratify patients to receive more aggressive or less aggressive therapy.

Adult↗

Comparison of three Glasgow multifactor prognostic scoring systems in acute pancreatitis.

Modifications have been proposed in an attempt to improve the clinical value of the original nine-factor Glasgow prognostic scoring system for acute pancreatitis. These include the omission of age or serum transaminase, reducing the factors to eight. Debate exists as to which system should be employed. Assessment of the individual factors in 198 attacks of acute pancreatitis treated conventionally revealed that only serum transaminase did not differ significantly between mild and severe outcome groups. Multivariate analysis demonstrated four factors (Pa,O2, white cell count, lactic dehydrogenase, and urea) with independent significance in predicting severity, while serum glucose, albumin and transaminase were least useful. Findings were similar when considering only patients with gallstone aetiology. The reduction of the prognostic factors to eight by the omission of either age or transaminase improved the predictive value of the scoring system, both when considering all attacks and those of gallstone aetiology alone. We suggest that serum transaminase should be omitted because: it shows no significant difference between mild and severe outcome groups, while age has prognostic significance; the system has greater sensitivity than if age is omitted; and the number of factors requiring emergency laboratory measurement for immediate prognostication is reduced by one.

Acute Disease↗

Evaluation of the prognostic value of triple node biopsy in early breast cancer.

The prognostic information obtained by triple node biopsy (low axillary, apical axillary and internal mammary nodes) in 693 patients with early breast cancer has been reviewed. Results show that tumour site within the breast influenced which nodal groups were involved. The low axillary node contributed the most useful prognostic information. The involved apical node carried the worst prognosis. Either the internal mammary node or a low axillary node when positive alone carried the same prognostic weight. When both nodes were positive the prognosis declined to the level associated with apical node positivity. A double node biopsy of the low axillary node and either the apical or the internal mammary node gave the same maximum prognostic information as a triple node biopsy. The triple node biopsy technique can be used to divide patients into groups with vastly different prognoses.

Adult↗

Prognostic significance of metastatic lymph node size in patients with gastric cancer.

BACKGROUND: Patients with gastric cancer that has metastasized to the lymph nodes are a heterogeneous population with a variable prognosis. Stratification of these patients into prognostic groups is necessary for optimal adjuvant therapy. METHODS: The study comprised 715 patients who had undergone curative resection of a gastric neoplasm. Lymph nodes were sectioned, stained with haematoxylin and eosin, and the diameter of the largest metastatic lymph node (MLN) was measured. Patients with metastatic nodes were divided into groups n1 and n2 according to the size of the MLN. The cut-off level was set at 7 mm by a two-sample log rank test; patients in group n1 had a MLN size of 7 mm or less and those in group n2 had a MLN of 8 mm or more. RESULTS: Patients were stratified into significant prognostic groups by both the Union International Contra la Cancrum (UICC) node (N) stage and MLN size (n group). The UICC N-stage subcategories were further divided into prognostic groups according to MLN size (n group). On multivariate analysis the MLN size remained independently significant in terms of overall and disease-free survival rates, and the UICC N stage was not significant, independently of the n group. Node-positive patients with fewer than 15 lymph nodes removed at operation could also be stratified into prognostic groups by the n group. Stratification according to the TNM stage and by MLN size was superior to existing UICC TNM staging. CONCLUSION: This new method may help clinicians to design a more appropriate treatment strategy for patients with gastric cancer.

Adult↗

Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) and endostatin stimulate and inhibit tumour angiogenesis respectively. Recent studies have demonstrated the prognostic value of serum levels of both VEGF and endostatin in patients with various types of cancer. Their significance in patients with hepatocellular carcinoma (HCC) remains unclear. METHODS: Serum VEGF and endostatin levels were measured by enzyme immunoassay in 108 patients with HCC before surgical resection and in 20 healthy controls. Preoperative serum VEGF and endostatin levels were correlated with clinicopathological features and long-term survival. RESULTS: Serum VEGF levels in patients with HCC were significantly higher than those in controls, but serum levels of endostatin were similar in the two groups. High serum levels of VEGF, but not endostatin, were significantly associated with venous invasion and advanced tumour stage. Patients with a serum VEGF level higher than median (over 245.0 pg/ml) had significantly worse overall and disease-free survival than those with a lower level (P = 0.012 and P = 0.022 respectively). On multivariate analysis, serum VEGF level was an independent prognostic factor (hazard ratio 1.86 (95 per cent confidence interval 1.10 to 3.92); P = 0.032). Serum endostatin levels did not have significant prognostic influence on overall or disease-free survival. CONCLUSION: A high serum level of VEGF is a predictor of poor outcome after resection of HCC. Serum VEGF, but not endostatin, may be a useful prognostic marker in patients with HCC.

Adolescent↗

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↗

Prognostic significance of grading and staging systems using MIB-1 score in adult patients with soft tissue sarcoma of the extremities and trunk.

BACKGROUND: The predictive value of histologic grading and staging systems for overall survival in different types of adult soft tissue sarcoma of the extremities and trunk is unclear. METHODS: Histologic slides from 193 patients with primary tumors were reviewed for diagnosis, and Ki-67 (MIB-1) immunostaining was performed for grading in all patients. Univariate and multivariate analyses were conducted to analyze the results from patients with soft tissue sarcomas as a group and among the six main histologic categories: malignant fibrous histiocytoma (n = 49 patients), liposarcoma (n = 48 patients), synovial sarcoma (n = 30 patients), spindle cell sarcoma (n = 24 patients), small round cell sarcoma (n = 15 patients), and others (n = 27 patients). The median follow-up was 50 months. RESULTS: Univariate analysis of soft tissue sarcomas showed that tumor size and depth, histologic type, MIB-1 score, grades based on three criteria (tumor differentiation/histologic type, necrosis, and either mitosis or MIB-1 score) and disease stage, as assessed by tumor size, depth, and grade, were associated with overall survival. Among these variables, grading and staging systems using the MIB-1 score had better predictive value compared with the MIB-1 score and standard grading and staging models in the main histologic categories. Because survival curves for the different tumor grades and stages showed similar trends between the different histologic types, multivariate analysis was conducted adjusting for age, gender, disease site, surgical margin, tumor size and depth, grade, stage, and histologic type. Consequently, Grade 3 emerged as the most significant adverse prognostic factor. Additional adverse prognostic factors were Stage III, Grade 2, a histologic type of spindle cell sarcoma, and patient age > 50 years at the time of presentation. The histologic type liposarcoma was identified as a favorable prognostic factor. CONCLUSIONS: The current results indicate that grading and staging systems using the MIB-1 score are very strong prognostic factors in patients with the main histologic types of soft tissue sarcoma. Specific assessment of histologic type should be carried out before deciding on treatment strategies.

Adolescent↗

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

BACKGROUND: The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. METHODS: From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). RESULTS: Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). CONCLUSIONS: The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials.

Adolescent↗

Prognostic factors in neuroendocrine small cell cervical carcinoma: a multivariate analysis.

BACKGROUND: The purpose of this study was to evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine (NE) cervical carcinoma. METHODS: All patients with NE cervical carcinoma diagnosed between 1979-2001 were identified from tumor registry databases at two hospitals. Data were collected from hospital charts, office records, and tumor registry files. The impact of clinical and pathologic risk factors on the survival of patients with small cell NE carcinoma of the cervix was evaluated using Kaplan-Meier life table analyses and log-rank tests. The independent prognostic factors found to be predictive of survival in univariate analysis were evaluated using Cox regression. All tests were two-tailed with P values < 0.05 considered significant. RESULTS: Thirty-four patients (median age, 42 years) were diagnosed with neuroendocrine cervical carcinoma, which included 21 with International Federation of Gynecology and Obstetrics (FIGO) Stage I disease, 6 with FIGO Stage II disease, 5 with FIGO Stage III disease, and 2 with FIGO Stage IV disease. Seventeen patients underwent a radical and 6 patients underwent a simple hysterectomy. Fourteen women received adjuvant therapy with pelvic radiation and/or cisplatin-based chemotherapy. Ten women received primary radiotherapy with (n = 5) or without (n = 4) chemotherapy and the remaining patient refused therapy. Women with early-stage (Stage I-IIA) disease had median survival rates of 31 months compared with 10 months in the advanced-stage (Stage IIB-IVB) group (P = 0.002). In univariate analysis, advanced stage (P = 0.002), tumor size >2 cm (P = 0.02), margin involvement (P = 0.016), pure versus a mixed histologic pattern (P = 0.04), margin status (P = 0.016), and smoking (P = 0.04) were considered poor prognostic factors. In multivariate analysis, smoking for early-stage patients and stage of disease in the overall population remained as independent prognostic factors of survival. CONCLUSIONS: Smoking and advanced stage are reported to be poor prognostic factors for survival in patients with NE small cell carcinoma of the cervix. Only those with early lesions amenable to extirpation are cured. The role of primary or postoperative radiation with or without chemotherapy is unclear and yields uniformly poor results, particularly in patients with advanced lesions. Clinical trials are needed.

Adult↗

Prognostic significance and interobserver variability of histologic grading systems for endometrial carcinoma.

BACKGROUND: The most widely used histologic grading system for endometrial carcinoma is the three-tiered International Federation of Gynecology and Obstetrics (FIGO) system. Although FIGO grading has significant predictive value, the reproducibility of Grade 2 is limited. Recently, a binary grading system was proposed based on the amount of solid growth, the pattern of myometrial invasion, and the presence of tumor cell necrosis. The authors analyzed and compared the prognostic significance and the interobserver variability of both grading systems and of the three criteria for the binary grading system. METHODS: Eight hundred patients with Stage I-III endometrioid endometrial carcinoma were reviewed and graded independently by two pathologists according to the three-tiered FIGO grading system and the novel binary grading system. RESULTS: The interobserver agreement for both systems was moderate, with 70% and 73% agreement rates for the FIGO (kappa = 0.41) and binary (kappa = 0.39) grading systems, respectively. When converting the FIGO grading system into an artificial, 2-tiered grading system (Grade 3 vs. Grades 1-2), the agreement was much better (agreement rate, 85%; kappa = 0.58). Of the 3 criteria for the binary grading system, amount of solid growth (< or = 50% vs. > 50%) had the greatest reproducibility (agreement rate, 80%; kappa = 0.50). Both the 2-tiered FIGO grading system and the binary grading system were significant predictors of local recurrence, distant recurrence, and disease-specific survival (hazard ratios [HRs]: 1.7, 2.5, and 2.6, respectively, for FIGO and 2.1, 4.1, and 3.8, respectively, for the binary grading system). The amount of solid growth also was a strong prognostic factor for these three endpoints (HRs: 2.4, 3.9, and 3.8, respectively). CONCLUSIONS: Both the binary grading system and the FIGO grading system had strong prognostic significance. Their reproducibility, however, was limited. A simple architectural binary grading system that divided tumors into low-grade lesions and high-grade lesions based on the proportion of solid growth (< or = 50% or > 50%) had superior prognostic power and greater reproducibility.

Aged↗

Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.

BACKGROUND: Advances in the diagnosis and surgical treatment of hepatocellular carcinoma (HCC) have improved the prognosis for patients with HCC who undergo liver resection. The objective of this study was to evaluate prognostic predictors for patients with HCC who underwent liver resection in a Japanese nationwide data base. METHODS: In this study, the authors analyzed 12,118 patients with HCC in a Japanese nationwide data base who underwent liver resection between 1990 and 1999 and compared them with a previous analysis of patients between 1982 and 1989. All patients were evaluated for prognostic factors. RESULTS: During the last decade, the increases in patients who were without hepatitis B virus surface antigen, who had small tumors, and who had portal vein invasion were noted. The 5-year overall survival rates for patients with HCC improved to 50.5%, compared with < 40% in the previous analysis. A multivariate analysis using a stratified Cox proportional hazards model according to associated liver disease indicated that age, degree of liver damage, alpha-fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were independent prognostic predictors for patients with HCC. Operative mortality decreased from 2.3% in 1990-1991 to 0.6% in 1998-1999. CONCLUSIONS: Outcomes and operative mortality rates in patients with HCC improved during the last decade. Age, degree of liver damage, alpha-fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were prognostic factors for patients with HCC who underwent liver resection.

Age Factors↗

Prognostic impact of TP53 mutation status for adult patients with supratentorial World Health Organization Grade II astrocytoma or oligoastrocytoma: a long-term analysis.

BACKGROUND: The goal of the current study was to retrospectively assess the prognostic impact of TP53 mutation status and P53 expression/accumulation on long-term outcome for adult patients with supratentorial World Health Organization (WHO) Grade II astrocytoma or oligoastrocytoma. METHODS: The authors revisited a previously published short-term data set containing information on 159 consecutive patients who were treated between 1991 and 1998. Each patient was screened for TP53 mutations and P53 overexpression/accumulation. The reference point for all analyses was the date of surgical treatment, and the date of last follow-up examination was August 2002. Overall survival, progression-free survival, postrecurrence survival, and time to malignant transformation were estimated using the Kaplan-Meier method, and potential prognostic factors were evaluated using the multivariate proportional hazards model. RESULTS: The median follow-up duration for survivors was 80.4 months (standard deviation, 33.0 months). TP53 mutations, which were present in 49.1% of all tumors, occurred preferentially in gemistocytic tumors (P < 0.05). In addition, the TP53 status of the primary tumor was predictive of the TP53 status of the recurrent tumor in all cases of disease recurrence. The 5-year overall and progression-free survival rates were 77.5% and 43.2%, respectively, and the risk of malignant transformation at 5 years postsurgery was 32.7%. Unfavorable prognostic factors with respect to survival duration included older age (> or = 50 years; P < 0.002), gemistocytic subtype (P < 0.01), and positive TP53 mutation status (P < 0.05), all of which were also negatively associated with progression-free survival (P < 0.05, P < 0.001, and P < 0.003, respectively). In contrast, positive TP53 mutation status was the only significant predictor of a reduction in time to malignant transformation (P < 0.03). P53 overexpression/accumulation did not exhibit prognostic relevance in any of the multivariate models constructed in the current study. CONCLUSIONS: TP53 mutations are common early events in the pathogenesis of WHO Grade II astrocytoma or oligoastrocytoma. In the current study, positive TP53 mutation status (but not P53 overexpression/accumulation) was found to be an independent unfavorable predictor of survival, progression-free survival, and time to malignant transformation. The therapeutic implications of these findings have yet to be determined.

Adult↗

Invasive cutaneous malignant melanoma in Sweden, 1990-1999. A prospective, population-based study of survival and prognostic factors.

BACKGROUND: The objective of the current study was to compile prospective, population-based data on cutaneous invasive melanomas in Sweden during the period from 1990 to 1999, to describe and analyze survival data and prognostic factors, and to make comparisons with previously published Swedish and international data. METHODS: Twelve thousand five hundred thirty-three patients, which included 97% of all registered melanomas in Sweden, were included and described. Among these, 9515 patients with clinical Stage I and II melanoma were included in an analysis of survival and in a univariate analysis, and 6191 patients were included in a multivariate analysis of prognostic factors. RESULTS: There was no significant change in melanoma incidence during 1990-1999. Favorable prognostic factors were found, especially in younger and female patients, resulting in a relative 5-year survival rate of 91.5%. In the multivariate analysis, significant factors that had a negative effect on survival were Clark level of invasion, Breslow thickness, ulceration, older patient age, trunk location, greatest tumor dimension, nodular histogenetic type, and male gender. CONCLUSIONS: During the period from 1990 to 1999, the 5-year survival of patients with malignant melanoma in Sweden was better compared with the previously reported rates in published, population-based studies from Sweden, probably as a result of better secondary prevention due to better knowledge and awareness by both patients and the medical profession. The more favorable prognostic factors and the change in melanoma location found in younger patients, compared with earlier reports, may reflect changes in clothing as well as tanning habits; however, a decrease also was found in Clark Level II and thin melanomas for the same patient group. The authors concluded that further improvements can be achieved with better access to health care and with the use of early melanoma detection campaigns.

Adolescent↗

The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma.

BACKGROUND: Loss of the cell-cycle inhibitory protein p27Kip1 is associated with poor prognosis in colorectal carcinoma. The decrease in p27Kip1 levels is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. Recently, Skp2 and Cks1 expression were found to be increased in some colorectal carcinomas, but their potential role as prognostic markers for survival is unknown. The present study was undertaken to assess the prognostic value of both Skp2 and Cks1 in colorectal carcinoma. MATERIALS AND METHODS: The expression of Skp2, Cks1, and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin-fixed, paraffin-embedded tissue sections from 80 patients with colorectal carcinoma. RESULTS: Overexpression of Skp2 and Cks1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation. A significant decrease in overall survival was observed in patients expressing high Skp2 or Cks1 levels, and in particular, patients with Stage II and III disease. Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27Kip1 expression. CONCLUSIONS: Results suggest that overexpression of Skp2 or Cks1 is strongly associated with poor prognosis and may thus be used as prognostic markers for overall survival in colorectal carcinoma.

Aged↗

Reclassification of patients with pT3 and pT4 renal cell carcinoma improves prognostic accuracy.

BACKGROUND: The significance of adrenal invasion and tumor thrombus in renal cell carcinoma (RCC) has been debated recently. The authors evaluated the associations of direct adrenal invasion, perinephric fat invasion, and tumor thrombus level with outcome to determine whether reclassification would improve the prognostic accuracy of the current primary tumor classification. METHODS: The authors studied 697 patients treated with nephrectomy for pT3 and pT4 RCC between 1970 and 2000. Associations with outcome were evaluated using Cox proportional hazards regression and prognostic accuracy was measured using the c index. RESULTS: Among patients with pT3 RCC, direct adrenal invasion was significantly associated with death from RCC (risk ratio, 2.11; P = 0.004). No significant difference in survival was found between patients with pT4 RCC and pT3 tumors with direct adrenal invasion (P = 0.490). Among patients with pT3b RCC, those with level I-III tumor thrombus were significantly more likely to die of RCC compared with patients harboring level 0 tumor thrombus (risk ratio, 1.62; P < 0.001). In addition, patients with fat invasion were more likely to die of RCC compared with pT3 patients without fat invasion (risk ratio, 1.87; P < 0.001). Therefore, patients with pT3 RCC were reclassified into 4 prognostic groups, and this reclassification significantly improved prediction of death from RCC compared with the current classification (c indices of 0.61 vs. 0.55, respectively). CONCLUSIONS: Direct adrenal invasion from RCC should be reclassified as pT4. In addition, the proposed reclassification for patients with pT3 RCC improved prognostic accuracy.

Adrenal Gland Neoplasms↗

Prognostic significance of the lymphocyte-to-neutrophil ratio in percutaneous fine-needle aspiration biopsy specimens of advanced nonsmall cell lung carcinoma.

BACKGROUND: The prognostic significance of tumor-infiltrating lymphocytes (TILs) in surgically resected carcinomas was reported. To apply this to inoperable nonsmall cell lung carcinomas (NSCLC) of Stage IIIB-IV, the authors estimated the occurrence of TILs using percutaneous fine-needle aspiration biopsy specimens, and tested the validity of this method. METHODS: The authors defined the L-N index as [L(S)/(L(S) + N(S)) - L(B)/(L(B) + N(B))], in which L(S) and N(S) denoted lymphocyte and neutrophil counts in the aspiration smear, and L(B) and N(B) denoted lymphocyte and neutrophil counts in the peripheral blood specimen. The cutoff value was set at twice the standard deviation of the L-N index of 41 smears contaminated with abundant blood. Retrospectively, the authors compared the survival rate of the group with a high L-N index (lymphocyte-dominant group) (n = 12) with the survival rate of the group with a low L-N index (lymphocyte-nondominant group) (n = 60). Then, they performed a prospective study and compared the survival rates of these 2 groups (n = 21 and n = 54). The Cox proportional hazards model was used to determine the effect of the L-N index as a continuous variable and other prognostic factors. The correlation (r) between the L-N index-based grouping (L-N grouping) and the histologic grade of TILs was studied among resected lung tumor specimens (n = 164). RESULTS: In the retrospective and prospective studies, the survival rate was significantly higher in the lymphocyte-dominant group than in the lymphocyte-nondominant group (P = 0.0019 and P = 0.0001). Using multivariate analysis, the L-N index was an independent prognostic factor. A significant correlation was noted between L-N grouping and histologic grade of TILs (r = 0.476). CONCLUSIONS: The L-N index of aspiration smears was found to be an independent prognostic factor for patients with advanced-stage NSCLC. L-N grouping was correlated with the histologic assessment of TILs.

Adult↗