Predictor Of Distant Metastasis Research Articles

Overexpression of Tyrosine Kinase B Protein as a Predictor for Distant Metastases and Prognosis in Gastric Carcinoma

Objective: Tyrosine kinase B (TrkB) is associated with aggressive behavior and poor prognosis in various cancers. Here we examined the association between TrkB expression and distant metastases/prognosis in gastric carcinoma (GC). Patients and Methods: We analyzed TrkB expression in 161 GC patients by immunohistochemistry and Western blot analysis. The correlation of TrkB mRNA and protein expression levels was examined in 10 patients by RT-PCR assay. Results: TrkB expression was of level 1 in 97 (60.2%) and level 2 in 64 (39.8%) patients. Patients with level 2 expression had a significantly higher incidence of distant metastases (p < 0.0001), well-differentiated tumors (p < 0.005), deeper depth of invasion (p < 0.005) and poorer disease-free and overall survival (p < 0.0001 each) compared to patients with level 1. Multivariate analysis identified the level of TrkB expression as an independent prognostic factor for both disease-free and overall survival (p < 0.01 and p < 0.0001, respectively). Both lymph node metastasis (odds ratio = 10.7) and TrkB expression (odds ratio = 9.3) were independent predictors of distant metastases. Conclusion: A high level of TrkB expression was observed in well-differentiated GC subtypes and is a predictor for distant metastases and prognosis in GC.

Method of Detection of Ipsilateral Breast Tumor Recurrence Following Breast Conserving Therapy is a Predictor of Distant Metastases

Results: We identified 112/809 patients with initial IMN+ disease (13.8%) detected on ultrasound, CT scan, PET/CT, and/or MRI studies. The majority of breast patients at our institution undergo an ultrasound for staging purposed; among the 90% of 809 patients with an ultrasound exam, the incidence of IMN+ disease was 12.3% (90/732). A small percentage of patients had additional chest CT, PET/CT, or MRI studies available. The detection rates of IMN+ on chest CT and PET/CT scan were 17.9% (39/218) and 31.3% (10/32), respectively. MRI data were incomplete for analysis. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (96/112) resulted in a clinical complete response of IMN disease in 72.1% of patients, with normalization of the involved IMN on imaging studies. All patients received radiation to the breast or chest wallandregionallymphaticsincludingtheIMNchainwithamediandoseto IMNsof60Gyiftheynormalizedafterchemotherapy, 66 Gy if they did not. The median follow-up of surviving patients was 41 months (range, 8-118 months). The actuarial 5-year IMN control rate, overall survival (OS), and disease-free survival (DFS) were was 86.8%, 69.2%, and 49.6%, respectively. Of the 96 patients who received radiotherapy with curative intent, the actuarial 5-year locoregional control rate was 84%. Sixteen patients were omitted from this analysis due to progression of disease prohibiting completion of multimodality therapy. Superior 5-year actuarial locoregional control was observed in patients with earlier T stage (89.7% vs. 60.4%, p = 0.0004) or a favorable response of IMN to chemotherapy (85.1% vs. 32.8%, p\0.0001). Furthermore, an improvement in 5-year actuarial OS was observed in patients with earlier T stage (82.2% vs. 56.6%, p = 0.003) and response of IMN to chemotherapy (75.9% vs. 40.3%, p\0.0001), compared to patients with T3-4 tumors and no response of IMN to chemotherapy. Conclusions: The incidence of IMN involvement in patients with advanced breast cancer is higher than clinically appreciated. Patients with IMN+ disease are potentially curative with multimodality therapy including radiation therapy to the IMN nodes, with half remaining disease-free at 5 years.

Merging microarray data from separate breast cancer studies provides a robust prognostic test

BackgroundThere is an urgent need for new prognostic markers of breast cancer metastases to ensure that newly diagnosed patients receive appropriate therapy. Recent studies have demonstrated the potential value of gene expression signatures in assessing the risk of developing distant metastases. However, due to the small sample sizes of individual studies, the overlap among signatures is almost zero and their predictive power is often limited. Integrating microarray data from multiple studies in order to increase sample size is therefore a promising approach to the development of more robust prognostic tests.ResultsIn this study, by using a highly stable data aggregation procedure based on expression comparisons, we have integrated three independent microarray gene expression data sets for breast cancer and identified a structured prognostic signature consisting of 112 genes organized into 80 pair-wise expression comparisons. A classical likelihood ratio test based on these comparisons, essentially weighted voting, achieves 88.6% sensitivity and 54.6% specificity in an independent external test set of 154 samples. The test is highly informative in assessing the risk of developing distant metastases within five years (hazard ratio 9.3 with 95% CI 2.9–29.9).ConclusionRank-based features provide a stable way to integrate patient data from separate microarray studies due to invariance to data normalization, and such features can be combined into a useful predictor of distant metastases in breast cancer within a statistical modeling framework which begins to capture gene-gene interactions. Upon further confirmation on large-scale independent data, such prognostic signatures and tests could provide a powerful tool to guide adjuvant systemic treatment that could greatly reduce the cost of breast cancer treatment, both in terms of toxic side effects and health care expenditures.

Predicting distant dissemination in patients with early breast cancer

Background. Prediction of distant metastases is of paramount importance in the knowledge and management of breast cancer patients. The objective of this study was to assess conventional prognostic factors in a large database of patients with early breast cancer, including those with small tumors diagnosed through regional screening, to determine the risk of distant dissemination. Methods. The study included 4 797 patients of the Stockholm database who did not receive systemic adjuvant treatments. The main endpoint was metastasis free-interval. Individual risks of distant metastasis were estimated using the regression coefficients of the significant prognostic factors in Cox multivariate analyses. For each level of metastatic risk the pattern of failure was analyzed by a model assuming competing risks. Results. The three independent significant prognostic factors were histologic tumor size, number of involved axillary lymph nodes and progesterone receptor level. However, the latter factor added limited additional information of borderline clinical significance. Thus, subsequent estimations were done with a prognostic score taking into account only the former two most performant factors in the whole population. The risk of distant metastasis of observed values of tumor size categories fitted with published results of a series containing significantly larger tumors. A large variation of tumor size predicts 10-year distant metastasis risk ranging from below 10% up to 90%. Tumors of 10 mm or less had a 10-year metastatic risk of less than 10%. Conclusions. The results of this study are consistent with a linear effect of tumor size, within the range of data, on 10-year distant dissemination probabilities. Further refinement on prognostic value is needed for tumors of 15 mm or less.

Evaluating distant metastases in breast cancer: from biology to outcomes

There is an urgent need to understand distant metastases in breast cancer as they are the most lethal form of recurrence and a major cause of mortality in patients. Some predictors for distant metastases, including nodal status, tumor grade, and hormonal status, are useful in identifying patients at increased risk for distant metastases. Adjuvant endocrine therapy has been the treatment of choice for postmenopausal women with hormone-sensitive breast cancer, and some therapies have shown significant reductions in the risk of distant metastases. Skeletal metastases in breast cancer are treated with bisphosphonates with a certain level of success. With more new agents undergoing clinical trials, a thorough review of the specific and long-term safety of these agents is essential, as is a better understanding of the deterioration in the quality of life and cost concerns of patients who develop distant metastases. Gene-expression profiling is a new entrant in the field of distant metastases diagnosis, which is largely successful in defining gene signatures that predict the development of distant metastases. This review will discuss the biology and the impact of distant metastases on outcomes for patients with breast cancer; it also encompasses the current status, emerging focus, and future perspectives in treatment of skeletal metastases in patients with breast cancer.

Predictors of Distant Metastasis and Mortality in Patients with Stage II Colorectal Cancer

The aim of our study was to determine clinical factors that predicted distant metastasis and mortality in patients with stage II colorectal cancer (CRC). A retrospective review of all patients admitted to the Dallas Veteran's Affairs Medical Center from 1998 to 2002 with stage II CRC was performed. Factors associated with distant metastasis and mortality were assessed by univariate analysis. Independent predictors of mortality and distant metastasis were assessed by multivariate analysis. Fifty-five patients with stage II CRC were identified (96% men, age 65 +/- 1.2 years old). Univariate analysis demonstrated that patients with distant metastasis (n = 13) had a history of alcohol intake (54% vs 20%; P = 0.029), less history of angiotensin-converting enzyme inhibitor use for the management of hypertension (31% vs 67%; P = 0.029), greater incidence of a rectal location for cancer (54% vs 12%; P = 0.004), an abdominoperineal resection (APR) for surgical management of their cancers (23% vs 0%; P = 0.011), and less negative lymph nodes examined during surgical resection (9 +/- 2.2 vs 15 +/- 1.2, P = 0.022). Follow-up of at least 3 years revealed 14 mortalities. Survivors had a less preoperative serum carcinoembryonic antigen level (5.9 +/- 0.9 vs 19.1 +/- 8.6; P = 0.031), an average less tumor depth involvement (T stage: 3.0 +/- 0.03 vs 3.2 +/- 0.11; P = 0.065), more negative lymph nodes examined at the time of surgical resection (14.0 +/- 1.3 vs 10.0 +/- 1.7; P = 0.058), less incidence of rectal cancer (21% vs 43%; P = 0.060), and none had undergone an APR (0% vs. 21%; P = 0.010). Multivariate analysis revealed that alcohol intake (P = 0.014; odds ration [OR] = 5.3), patients undergoing an APR (P = 0.011; OR = 25), and less frequency of angiotensin-converting enzyme inhibitor use (P = 0.007; OR = 4.5) independently predicted distant metastasis, whereas preoperative carcinoembryonic antigen (P = 0.038; OR = 2.8) and patients undergoing an APR (P = 0.019; OR = 25) independently predicted mortality.

Local-regional relapse and distant metastasis in conservatively managed triple negative early stage breast cancer

594 Background: Triple negative (TN) basal-like breast cancers (Negative for ER,PR,HER2/neu) represent an aggressive phenotype, with unique clinical and pathologic features. The purpose of this study was to determine the prognostic significance of this classification with respect to local-regional relapse and distant metastasis in a cohort of conservatively managed breast cancer patients. Methods: A large data base of conservatively managed breast cancer patients with long term follow-up, in which all three immunhistochemical markers, ER,PR and HER2/neu were available was reviewed. Patients were classified as TN if they tested negative for all three markers. Of 442 patients in the data base with all three markers available, 100 were classified as TN. All clinical, pathologic, outcomes and molecular marker data were entered into a computerized database. Results: As of September 2005, with a median follow-up of 7 years, of the 442 patients in the study there have been 50 in-breast relapses, 10 nodal relapses, 68 distant relapses and 62 deaths. Compared with the other subtypes, the TN cohort had a poorer overall survival (67% vs 75%, p = .096), poorer distant metastasis-free rate (61% vs 75%, p = .002), poorer cause-specific survival (67% vs 78%, p = .03), and poorer nodal relapse-free rate (93% vs 99%, p = .021). In a multivariate Cox regression analysis, TN subtype was an independent predictor of distant metastasis (HR=2.6, CI 1.53–4.35, p = .004) and cause- specific survival (HR= 2.36, CI 1.28–4.38, p= .006). There was no significant difference in local (in-breast) control between the TN and other subtypes. BRCA testing was performed on 85 patients in this cohort, of whom 8 had deleterious mutations in BRCA1 and 6 had deleterious mutations in BRCA2. Of 8 BRCA1 mutant patients 7 were classified as TN, while only 1 of 6 BRCA2 patients were TN (p &lt; .001). Conclusions: Patients classified as TN have a poor prognosis with respect to overall, disease free and cause specific survival. However there was no evidence that these patients are at higher risk for local relapse following conservative surgery and radiation. BRCA1 mutant patients develop predominantly TN tumors. No significant financial relationships to disclose.

Expression profiling and prediction of distant metastases in head and neck squamous cell carcinoma

Background: For breast and prostate cancer, a gene expression signature of the tumour is associated with the development of distant metastases. Regarding head and neck squamous cell carcinoma (HNSCC), the...

Usefulness of Plasma Vascular Endothelial Growth Factor in the Diagnosis of Pancreatic Carcinoma

This study aimed to examine the usefulness of plasma vascular endothelial growth factor (p-VEGF) in patients with pancreatic carcinoma (PC) as a tumor marker for PC in comparison with chronic pancreatitis (CP) and to clarify the relationship between p-VEGF and the clinicopathological features of PC. The subjects were 69 patients with PC, 35 with CP, and 26 healthy volunteers (control group). The p-VEGF levels were measured by enzyme-linked immunoassay. p-VEGF levels were significantly higher in the PC group compared with the CP and control groups (P < 0.0001). A cut-off level of 149.5 pg/mL, discriminating between PC and CP, was determined based on a receiver operating characteristic curve. Using this cut-off level, the sensitivity was 60%, specificity was 96%, and accuracy was 73%. Patients with PC with distant metastases exhibited a significantly higher level of p-VEGF compared with those without metastasis (P = 0.0113). Multivariate analysis indicated that a high level of p-VEGF was an independent prognostic factor, and a significant association was observed between p-VEGF and median survival time (P = 0.0092). p-VEGF proved useful in differentiating between PC and CP, and in patients with PC, a high level of p-VEGF may be a predictor of distant metastases and poor prognosis.

Variables Predicting Distant Metastases in Thyroid Cancer

Distant metastases from thyroid cancer are uncommon and have a variable prognosis. We present a series of patients with distant metastases to determine which patients are at risk of developing distant disease and to examine the significant prognostic variables. Retrospective chart review of 30 patients with distant metastases compared with 633 controls from the Mount Sinai Thyroid Cancer Database and literature review. The prevalence of distant metastases was 4.5%, and median follow-up of survivors was 12.7 years. Histologic type was Hurthle cell carcinoma in 3, follicular in 3, papillary in 19, and 5 patients had focal anaplasia either in the primary site or regional metastases. Predictors for distant metastases, locoregional control, and survival were analyzed. Cumulative survival for patients with distant metastases was 49.5% at 10 years and 12.9% at 20 years. Site of metastases was lung in 26, bone in 11 and brain in 1 patient, with 8 patients having multiple sites. The median time to diagnosis of distant metastases was 3 months. Variables that predicted for development of distant disease were male sex, age, size, extrathyroidal extension, regional metastases, and elevated thyroglobulin. Survival in patients without distant disease was significantly better than those with distant metastases (P < .001). Variables that predicted poor outcome in patients with distant metastases on analysis were age greater than 45 years (P = .003) and histologic type of thyroid cancer (P = .009). Although patients with thyroid cancer and distant metastases may live prolonged periods with disease, it does significantly impact on patient survival. Age remains an important variable in both predicting for development of distant metastases and also influences long-term survival in patients with existing distant metastases.

THE MEMBRANE PROTEASES ADAMS AND HEPSIN ARE DIFFERENTIALLY EXPRESSED IN RENAL CELL CARCINOMA. ARE THEY POTENTIAL TUMOR MARKERS?

ADAMs (a disintegrin and metalloproteinases) as cell surface proteins with adhesion and protease activity, and hepsin as a transmembrane protease have important roles in many biological processes. We assessed the expression of various ADAMs and of hepsin in human renal cell carcinoma (RCC), and correlated expression with clinicopathological data. mRNA expression of ADAM-8, 17, 19, 28, TS1 and TS2, and of hepsin was investigated in paired tissue samples from cancerous and noncancerous parts of the kidneys of 27 patients with RCC who underwent tumor nephrectomy. Measurements were performed by quantitative real-time reverse transcriptase-polymerase chain reaction on a LightCycler instrument (Roche Applied Science, Mannheim, Germany). The data were related to housekeeping gene porphobilinogen deaminase mRNA. All ADAMs except ADAM-TS1 were significantly higher but hepsin was less expressed (at least p <0.05) in cancerous vs matched noncancerous tissue. Expression was differentially related to tumor stage. ADAM-8 and ADAM-TS2 over expression as well as decreased hepsin expression were associated with shorter patient survival. The Cox proportional hazards regression model revealed that ADAM-TS2 was an independent prognostic factor for cancer related death. ADAM-8 was the best predictor of distant metastases. The differential expression of hepsin and ADAMs suggests early and late involvement of membrane proteases in the development of RCC. Their association with the clinical outcome illustrates their potential usefulness as biomarkers for RCC.

S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer.

Distant metastasis is the predominant cause of death in early-stage non-small cell lung cancer (NSCLC). Currently, it is impossible to predict the occurrence of metastasis at early stages and thereby separate patients who could be cured by surgical resection alone from patients who would benefit from additional chemotherapy. In this study, we applied a comparative microarray approach to identify gene expression differences between early-stage NSCLC patients whose cancer ultimately did or did not metastasize during the course of their disease. Transcriptional profiling of 82 microarrays from two patient groups revealed differential expression of several gene families including known predictors of metastasis (e.g., matrix metalloproteinases). In addition, we found S100P, S100A2, trypsinogen C (TRY6), and trypsinogen IVb (PRSS3) to be overexpressed in tumors that metastasized during the course of the disease. In a third group of 42 patients, we confirmed the induction of S100 proteins and trypsinogens in metastasizing tumors and its significant correlation with survival by real-time quantitative reverse transcription-PCR. Overexpression of S100A2, S100P, or PRSS3 in NSCLC cell cultures led to increased transendothelial migration, corroborating the role of S100A2, S100P, and PRSS3 in the metastatic process. Taken together, we provide evidence that expression of S100 proteins and trypsinogens is associated with metastasis and predicts survival in early stages of NSCLC. For the first time, this implicates a role of S100 proteins and trypsinogens in the metastatic process of early-stage NSCLC.

Increased mRNA expression of ADAMs in renal cell carcinoma and their association with clinical outcome

ADAMs (a disintegrin and metalloproteinase) are cell-surface proteins with adhesion and protease activity which play important roles in many biological processes. Little is known about their role in cancer. The aim of the study was to assess the quantitative expression of the ADAMs in human renal cell carcinoma (RCC) and to associate expression levels with clinicopathological data. We investigated the mRNA expression of ADAM-8, -17, -19, -28, ADAM-TS1, and ADAM-TS2 in paired tissue samples from cancerous and non-cancerous parts of the kidneys of 27 patients with RCC who underwent tumour nephrectomy. Measurements were performed by means of the quantitative real-time RT-PCR on a LightCycler instrument. ADAM-8, -17, and -19 were significantly higher expressed (p<0.05 at least) in cancerous compared with the matched non-cancerous tissue in pT1 and > or =pT2 tumours, ADAM-28 and ADAM-TS2 only in pT1 tumours, and ADAM-TS1 was not differently expressed. All ADAMs except ADAM-TS1 showed an increase of expression in the non-cancerous tissue with rising pT stage suggesting an early involvement of ADAMs in the development of RCC. The expression of ADAM-8 was related to a shorter survival of patients and was the best predictor of distant metastases. Our results indicate a potential role for ADAMs in RCC and that the overexpression might be a useful predictive tool.

Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes.

To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P =.04) and a clinical response to chemotherapy > or = 50% (P =.003) were associated with negative axillary status at dissection. An initial tumor size < or = 3 cm (63 patients) was associated with pCR of the primary tumor (P =.02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P =.003), absence of residual nodal disease (P =.01), and pCR of the tumor (P =.05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% +/- 14.9% among patients with no involved nodes at the time of surgery and 48.7% +/- 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age < or = 40 years (P =.002), persistence of nodal involvement (P =.03), and S-phase fraction greater than 4% (P =.02). Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.

Prediction of Distant Metastases after Curative Surgery for Rectal Cancer

Background. This study was performed to define selection criteria for adjuvant therapy in rectal cancer.Materials and methods. An immunohistochemical analysis using nine monoclonal antibodies against CEA, CD15s, CD44v6, DCC, E-cadherin, EGF-R, NM23, PAI-1, and P53 was performed on paraffin sections of two matched (age, gender, UICC stage [I–III], year of operation [1982–1991]) groups of patients (n = 2 × 64) with rectal carcinoma curatively treated by surgery alone. The two groups differed only with regard to metachronous distant metastatic spread. In order to exclude the influence of surgery, all patients had to meet the selection criterion “free of locoregional disease.” Follow-up was prospective (median 80 months). Conventional staining procedures and immunohistochemical evaluation were used. Tumor grading and lymphatic and extramural venous invasion were also investigated. Analysis was performed with Fisher's exact test and Kaplan–Meier estimates of disease-free survival (log rank). The Cox model was used for multivariate analysis.Results. In univariate analysis only grading (P < 0.001) and extramural venous invasion (P < 0.001) correlated significantly with metachronous metastases. In multivariate analysis, beside grading (P = 0.010) and extramural venous invasion (P = 0.011), CD15s (P = 0.042) was also of significance. All other immunohistochemical markers failed.Conclusions. The histopathological parameters grading and extramural venous invasion appear to be acceptable predictors of metachronous distant spread in curatively resected rectal cancer. In contrast to the immunohistochemical markers, grading seems to better reflect the individual tumor phenotype and its behavior.

Incidence and Prognostic Significance of Complete Axillary Downstaging After Primary Chemotherapy in Breast Cancer Patients With T1 to T3 Tumors and Cytologically Proven Axillary Metastatic Lymph Nodes

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P = .04) and a clinical response to chemotherapy ≥ 50% (P = .003) were associated with negative axillary status at dissection. An initial tumor size ≤ 3 cm (63 patients) was associated with pCR of the primary tumor (P = .02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P = .003), absence of residual nodal disease (P = .01), and pCR of the tumor (P = .05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% ± 14.9% among patients with no involved nodes at the time of surgery and 48.7% ± 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age ≤ 40 years (P = .002), persistence of nodal involvement (P = .03), and S-phase fraction greater than 4% (P = .02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.

Predictors of distant metastasis at presentation in breast cancer: a study also evaluating associations among common biological indicators

To investigate the correlation among some of the commonly used clinical, pathological factors and newer biological indicators, and to identify the independent predictors of distant metastasis at presentation in patients with breast cancer. The pathological specimens from 73 patients with breast cancer were retrospectively evaluated by immunohistochemistry. Data on 13 biological indicators; ER, PR, P53, c-erbB-2, PCNA, CEA, Ki-67, Vimentin, Ulex, Nm23, Cathepsin D, Factor VIII, PS2 together with clinical and pathological factors were collected. A number of highly significant correlations were found among the biological indicators studied. By logistic regression analysis, the predictors of distant metastasis at presentation in univariate tests were tumor diameter, number of lymph nodes involved, P53, c-erbB-2 and grade. In multivariate analysis, tumor diameter (P = 0.042, HR: 1.88(1.02-3.44)), c-erbB-2 expression (P=0.035, HR: 18.20 (1.23-268.66)) and grade (P=0.010, HR: 8.05(1.66-39.00)) retained their significance. Our findings show that inactivation of suppressor genes, expression of oncogenes, loss of differentiation, augmentation of proliferative activity, metastatic potential, angiogenesis and hormone receptor status are all interrelated facets of breast cancer pathogenesis. Patients with tumors overexpressing c-erbB-2 or with bigger or higher-grade tumors probably need to be more carefully evaluated for the presence of distant metastasis, thus be better staged, at presentation. This may be a new reason to test c-erbB-2 routinely in all patients with breast cancer in addition to its well-known prognostic and predictive uses.

Prediction of distant metastases in breast cancer from blood flow in primary nodule estimated using kinetic analysis of 99Tcm-MIBI uptake

Riannel, Ju. E.; Barysheva, E. V.; Mihailovic, J.; Velichko, S. A.; Slonimskaya, E. M.; Stefanovic, L.; Ussov, W. Yu.

139 Predictors of distant metastasis 7 years after a rising PSA in prostate cancer patients treated with external beam radiotherapy

139 Predictors of distant metastasis 7 years after a rising PSA in prostate cancer patients treated with external beam radiotherapy

Increased expression of CD44v6 mRNA significantly correlates with distant metastasis and poor prognosis in gastric cancer.

Expression of CD44 and its variants is associated with clinically aggressive behavior of some human cancers. The present study was undertaken to determine the expression level of these CD44 mRNAs in relation to the clinicopathologic features and prognosis of gastric cancer. Using reverse transcription polymerase chain reaction followed by Southern blotting, we examined the expression of the standard and variant (v6 and v9) forms of CD44 mRNA in 73 cases of gastric cancer. We determined the ratio of mRNA expression in cancer tissue to normal tissue (T/N ratio) and evaluated the correlations of the ratio with clinico-pathologic features, tumor progression and prognosis. The expression level of the standard form of CD44 (CD44s) mRNA correlated with peritoneal dissemination only, and that of CD44v9 mRNA did not significantly correlate with any clinicopathologic factor. The expression level of CD44v6 mRNA was significantly higher in patients with lymph node metastasis and liver metastasis. In 48 curatively resected patients, the expression level of CD44v6 mRNA correlated with the site of recurrence. Furthermore, there was a significant survival advantage in patients with low expression of CD44v6 mRNA compared with those with high expression. The level of CD44v6 mRNA expression may be a potential prognostic indicator and may be useful as a predictor for distant metastasis and recurrence in patients with gastric cancer.