Independent Predictor Of Early Recurrence Research Articles

O-119 Preoperative SUV of NSCLC is an independent predictor of early recurrence after complete resection

O-119 Preoperative SUV of NSCLC is an independent predictor of early recurrence after complete resection

Tissue microarray analysis reveals prognostic significance of syndecan-1 expression in prostate cancer.

Tissue microarrays (TMA) have recently emerged as powerful tools to rapidly analyze the clinical significance of new molecular markers in human tumors. Here, we have tested several molecular markers on a prostate TMA containing 637 different specimens. The specimens were from 551 patients with prostate cancer and long-term follow-up information on progression (median 5.3 years), tumor-specific and overall survival (median 5.9 years). Eighty-six specimens from benign prostatic hyperplasia were included as controls. Expression of Ki67, Bcl-2, p53, CD-10 (neutral endopeptidase), and syndecan-1 (CD-138) was analyzed by immunohistochemistry. Gleason grade and Ki67 Labeling Index (LI) were independent predictors of early recurrence and poor survival. Bcl-2 predicted early recurrence, whereas p53 was associated with poor survival. Syndecan-1 overexpression also predicted early recurrence and was significantly associated with tumor specific survival, high Gleason grade, Ki67 LI, and Bcl-2 overexpression. Neoadjuvant hormonal therapy was associated with overexpression of Bcl-2 and inhibition of Ki67 LI and CD-10, but did not affect the expression of the remaining markers. The results of this TMA study confirm a dominant prognostic significance of Gleason grading and Ki67 LI in prostate cancer, as compared to a less pronounced role of Bcl-2, and p53. We identified syndecan-1 as a new prognostic factor and provide evidence for an androgen-dependent regulation of CD-10 expression.

Risk factors for early recurrence after ischemic stroke: the role of stroke syndrome and subtype.

Information regarding risk factors for early recurrence is limited. Our aim was to identify the clinical predictors of early recurrence after ischemic stroke. We prospectively examined 297 patients (mean age, 72.0+/-8.4 years) hospitalized with ischemic stroke to identify recurrent strokes occurring within 90 days of the index stroke. Survival free of recurrence was estimated using Kaplan-Meier analysis stratified by demographic variables; vascular risk factors; stroke syndrome, subtype, vascular territory, and severity; scores on the Barthel Index and Mini-Mental State Examination during hospitalization; blood pressure on admission; and selected laboratory data. We estimated the relative risk (RR) of early recurrence associated with those variables using proportional hazards analysis. We identified 22 recurrent events in the first 90 days after the index stroke, resulting in an early stroke recurrence rate of 7.4%, and death occurred immediately after recurrence in 6 of the 22 patients. A major hemispheric stroke syndrome (RR=2.9; 95% confidence interval [CI]=1.2 to 7.1), atherothrombotic stroke mechanism (RR=3.3; CI=1.3 to 8.3), and atrial fibrillation (RR=2.2; CI=0.8 to 6.1) were independent predictors of early recurrence, after adjustment for demographic variables. Conclusions-Early recurrence was frequent and resulted in increased mortality. Attention to the clinical features of the index stroke, including the presenting syndrome and the ischemic mechanism, and the recognition of atrial fibrillation may help in the selection of patients for the initiation of targeted interventions to prevent early recurrence and subsequent mortality.

POSTOPERATIVE RECURRENCE OF CROHN'S DISEASE IN CHILDREN

Background: Postoperative recurrence of Crohn's disease (CD) is well characterized in adults with symptomatic recurrence rates of 10% at 1 yr, 30% at 3 yrs and 40-50% at 5 yrs. To date, only one retrospective study has critically analyzed postoperative recurrence of CD in children. Methods: A retrospective analysis of patients with CD seen at CHOP from 1978-1996 who underwent resective surgery before 21 yrs of age was performed. Postoperative recurrence was defined as 1) CD-related symptoms with radiologic or endoscopic evidence of recurrence, or 2) an increase in Pediatric Crohn's Disease Activity Index (PCDAI) of >30 points with response to subsequent escalation in medical therapy. Recurrence rates were calculated using actuarial (Kaplan-Meier) log-rank analysis and correlated to specific historical, surgical and pathological factors. Results: Out of 339 pts with CD, 79 (23%) pts had resective surgeries. Records were available for 67 (85%) surgeries. 8 (12%) had colonic disease, 4 (6%) small bowel (SB) disease, 39 (58%) had ileocecal disease, and 16 (24%) had disease diffusely involving both the SB and colon. Average followup was 3.6 yr (med: 2.8 yr, range: 0-16.5 yr). Recurrence rate was 17% at 1yr, 38% at 3yrs, and 60% at 5 yrs. By univariate analysis, lymphopenia at surgery (p=0.05), or preoperative use of 6-mercaptopurine (6-MP) (p=0.004) or metronidazole (p=0.04) was associated with shorter recurrence free intervals (RFI) following surgery. Recurrence rate did not correlate with preoperative duration of CD or perforating indication for surgery. Patients with disease limited to the colon had a high rate of recurrence (Median RFI=1.16 yr), while those who had ileocecal disease had a low rate of recurrence (median RFI=4.36 yr), and those with diffuse disease (involving both the colon and SB) had an intermediate rate (median RFI=2.95 yr) (p=0.01). Multivariate analysis revealed that the use of 6-MP (p=0.0005) and a high PCDAI at the time of surgery (p=0.01) were independently associated with increased postoperative recurrence rates. Conclusions:Children with CD have a higher postoperative symptomatic recurrence rate than previously described in the adult literature. Children with colonic disease are at high risk for recurrence, those with diffuse disease are at intermediate risk, and those with ileocecal disease are at low risk for recurrence. Preoperative use of 6-MP and high PCDAI at surgery are independent predictors of early recurrence.

Sialomucin expression is associated with erbB-2 oncoprotein overexpression, early recurrence, and cancer death in non-small-cell lung cancer.

Mucin production, when heavily sialylated, can promote cancer cell invasion and metastasis, and modulate the immune recognition system of the host. To explore the prognostic implication of sialomucin expression in lung cancer, we studied 116 patients with non-small-cell lung cancer (NSCLC). Tumor specimens were stained immunohistochemically with monoclonal antibodies (mAbs) against mucin glycoprotein (17Q2, HMFG2, SM3), and histochemically with periodic acid-Schiff/alcian blue to differentiate neutral mucin from acid mucin, and with high-iron diamine/alcian blue to differentiate sialomucin from sulfomucin. The expression status of two established molecular prognostic factors, the p53 and erbB-2 oncoproteins, were evaluated immunohistochemically. The staining was performed on two separately archived, paraffin-embedded tumor blocks for each patient, with normal lung as a control. Correlations were subsequently made among stains and various clinicopathologic factors. All analyses were blinded, and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Associations were established among adenocarcinoma histotype and erbB-2 overexpression, sialomucin expression, and 17Q2 and HMFG2 immunohistochemical positivity (p < 0.05). Sialomucin expression was closely linked to erbB-2 overexpression (p = 0.01). Significant univariate predictors (p < 0.05) of recurrence and cancer death were surgical stage, p53 expression, erbB-2 overexpression, and sialomucin expression. These four factors remained as independent predictors of early recurrence (p < 0.05) after multivariate analysis. For cancer death prediction, p53 and sialomucin expression had a marginal effect. We concluded that sialomucin expression is also a poor indicator of prognosis, which is associated with erbB-2 oncoprotein overexpression, early postoperative recurrence, and cancer death in NSCLC.

Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients.

The Eastern Cooperative Oncology Group (ECOG) entered 766 patients onto two prospectively randomized surgical adjuvant clinical trials for lymph node-positive breast cancer (T1-3N1M0). Ninety-five percent (n = 728) of eligible patients have complete information on the prognostic covariables under study (tumor necrosis [TN], tumor size, number of positive lymph nodes, age) and a median follow-up duration of 10.3 years. TN was defined as confluent cell death in invasive areas of primary cancers, visible at 4 x objective lens magnification. Cox proportional hazards models were used to estimate presence versus absence of TN effects on clinical outcomes over full cross-stratification of variables, including delivery of chemotherapy versus observation only. Time-varying effects were modeled using spline functions of time, and by fixing proportional hazards models separately in the time periods 0 to 2 and 2+ years. Presence of TN was an independent predictor for time to recurrence (TTR) (P = .007) and for survival (P = .0003) in the overall 10-year follow-up period. Presence of TN was also an independent predictor for TTR and for survival (each P < .0001) in the period 0 to 2 years after diagnosis. Spline function time-modeling calculations showed different hazard ratios in the TN-present (TN+) versus TN-absent (TN-) groups for both TTR and survival (each P < .0001). This difference is changing over time (P = .0001 for TTR, P = .0005 for survival). Once a patient has been disease-free beyond 2 years after diagnosis, presence or absence of TN is irrelevant to future prognosis. Confluent TN of any dimension in invasive areas of lymph node-positive breast cancer is an independent predictor for early recurrence and death from the disease.

Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases.

We used monoclonal antibodies to identify occult micrometastases in the bone marrow of 49 patients with operable (stage I and II) breast carcinoma. Follow-up (mean, 29 months; median, 30 months) revealed that 12 patients recurred. The presence of bone marrow micrometastases (BMM) was significantly associated with early recurrence (P less than .04). The estimated 2-year recurrence rate for patients with no BMM detected (BMM-) was 3%; in patients with BMM, the 2-year recurrence rate was 33%. When BMM and axillary lymph node (LN) status were combined, groups of patients at low risk (LN-, BMM-; 2-year recurrence rate, 0%) and high risk (LN+, BMM+; 2-year recurrence rate, 42%) for early recurrence were identified. Bone marrow tumor burden was related to early recurrence. Among patients with BMM, those who did not recur had on average fewer extrinsic cells in their marrow than those who recurred (15 v 43 cells, respectively). Multivariate analysis comparing BMM, LN+ versus LN-, and tumor size (less than or equal to 2 cm v greater than 2 cm) revealed no factor independently associated with early recurrence. Peripheral tumor burden of BMM (0 or less than 10 extrinsic cells v greater than or equal to 10 extrinsic cells) was the only independent predictor of early recurrence (P less than .003). In conjunction with conventional prognostic factors, particularly axillary LN status, evaluation for BMM might be used to stratify patients for adjuvant treatment programs. Because this pilot study involved few patients with short-term follow-up, the results should be interpreted with caution. The examination of bone marrow for micrometastases remains an experimental procedure; the clinical usefulness of the test will be established through larger studies with long-term follow-up.

Cathepsin D and Prognosis in Breast Cancer

We investigated the possibility that cathepsin D, an estrogen-induced lysosomal protease, might have value as a prognostic factor in breast cancer by studying frozen tissue specimens from 397 patients. We measured the 34-kd mature form of the enzyme by Western blot assay and densitometry. Among 199 patients with node-negative disease, but not among 198 with node-positive disease, high levels of cathepsin D proved to be a significant predictor of reduced disease-free survival (median follow-up, 64 months), either as a continuous variable (log cathepsin D; P = 0.018) or as a dichotomous variable with an optimized cutoff point (P = 0.0001). Results were similar for overall survival (P = 0.009 and 0.0001, respectively). Relating the level of cathepsin D to other prognostic factors in the patients with node-negative disease, we found an association with aneuploidy but none with estrogen or progesterone receptors, tumor size, or the age of the patient. In multivariate analyses, a high level of cathepsin D was the most important independent factor in predicting shorter disease-free and overall survival in patients with node-negative disease. As compared with the risk in women with low levels of cathepsin D, the relative risk of tumor recurrence was 2.6 (95 percent confidence interval, 1.6 to 4.4) and the relative risk of death was 3.9 (95 percent confidence interval, 2.1 to 7.3) among those with high levels of cathepsin D. For disease-free survival, cathepsin D status was predictive of outcome primarily among those with aneuploid tumors; the actuarial five-year recurrence rates of aneuploid tumors were 60 percent among women with high levels of cathepsin D and 29 percent among those with low levels, as compared with 22 percent for all diploid tumors. We conclude that cathepsin D may be an independent predictor of early recurrence and death in node-negative breast cancer.

Lymphocytopenia as an independent predictor of early recurrence in breast cancer.

Lymphocytopenia as an independent predictor of early recurrence in breast cancer.