The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma.

INTRODUCTION: Resistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients. METHODS: We analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients' body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis. RESULTS: Median splenic volume change was 10% (ranging from - 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1-4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1-6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly. CONCLUSION: Our findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.

Greater financial toxicity correlates with increased psychological distress and lower quality of life among Turkish cancer patients.

PURPOSE: This study aims to investigate the factors that influence financial toxicity and its effects on both quality of life and psychological distress in Turkish cancer patients. METHODS: Data from 400 cancer patients receiving chemotherapy at a public university in Turkey was analyzed. The Comprehensive Score for Financial Toxicity (COST), Patient Health Questionnaire for Depression and Anxiety (PHQ-4), and Functional Assessment of Cancer Therapy-General (FACT-G) were used to measure financial toxicity, psychological distress, and health quality of life, respectively. RESULTS: Patients' median COST score was 22 (SD = 10.1; range: 1-44) and was consistent with mild financial toxicity. Financial toxicity was associated with lower education level (p < 0.001), lower monthly income (p < 0.001), being a woman (p = 0.021), living in another city (p = 0.012), and previous cancer surgery (p = 0.02). A negative and statistically significant correlation was found between financial toxicity and quality of life (r = - 0.139; p = 0.005) and psychological distress (r = - 0.398; p < 0.001). CONCLUSION: This investigation demonstrated that financial toxicity was a significant determinant of quality of life and psychological distress.

LAG-3 expression in tumor microenvironment of triple-negative breast cancer.

BACKGROUND: This study aimed to evaluate the expression of lymphocyte activation gene-3 (LAG-3) and its relationship with programmed cell death ligand-1 (PD-L1) in triple-negative breast cancer (TNBC). METHODS: : LAG-3 and PD-L1 was evaluated in tumor-infiltrating lymphocytes (TILs) using immunohistochemistry (IHC). The chi-square test was used to estimate the associations between LAG-3, PD-L1 and clinicopathological characteristics. Correlation between LAG-3 stromal TIL (sTIL), LAG-3 intraepitelial TIL (iTIL) and PD-L1 was assessed with using the Spearman's correlation coefficient. Survival analysis was performed using the Kaplan-Meier method. RESULTS: The percentages of LAG-3 sTIL+, LAG-3 iTIL+, PD-L1+ tumor cells and PD-L1+ inflammatory cells were 52%, 42%, 14% and 70%, respectively. A strong positive correlation between LAG-3 sTIL and LAG-3 iTIL (r = 0.874, p < 0.001) and a moderate positive correlation between LAG-3 sTIL and PD-L1 (r = 0.584, p < 0.001) were found. LAG-3 and PD-L1 status did not significantly affect overall survival (OS) (HR: 0.56 (95% CI: 0.15-2.11) (p = 0.397), HR: 2.70 (95% CI: 0.56-13.02) (p = 0.215), respectively). DISCUSSION: High levels of LAG-3 and PD-L1 expression were detected in patients with TNBC. Although their contribution to survival could not be determined, the high expression rates of PD-L1 and LAG-3 may help identify the subgroup of TNBC that would benefit from immunotherapy.

Current status of biosimilars in Turkey: A survey among medical oncologists.

INTRODUCTION: To evaluate biosimilar understanding and preference trends of medical oncologists in Turkey. METHODS: A survey consisting of 24 multiple-choice questions with checkbox answers was conducted among medical oncologists. The questionnaire was divided into five parts to some intentions: demographic characteristics, general knowledge about biosimilars, knowledge about local approval and reimbursement issues, individual preference trends, and ranking the knowledge of their own. All answers were analyzed as whole cohort, specialists and fellows. RESULTS: Fellows (n = 47) consisted 42%, and academic clinicians (n = 37) consisted 35% of the participants. In the whole cohort, the overall rate of correct answers was 55.1% in the general knowledge about the biosimilars part, and 26.7% in the local approval and reimbursement issues part. At all, 57.7% of the participants declared that they object to switch from a reference product to a biosimilar product. The rate of those who defined themselves as extremely knowledgeable decreased from 8.1% to 2.7% in the whole cohort at the end of the survey. CONCLUSION: The need for more accurate and clarified local regulations and education emerging in the biotechnology era must be met.

The relationship between clinical and pathological findings and FDG - PET uptake in metastatic colorectal cancers.

BACKGROUND: In metastatic colorectal cancer (mCRC), the genetic structure and cell metabolism of the primary tumor lesion might be different from metastatic lesions. It is thought that cell-level glucose metabolism may differ due to the difference in RAS wild and mutant mCRC patients' prognosis. In this study, we aimed to compare 2-deoxy-2-[fluorine-18]-fluoro-D-glucose Positron Emission Tomography (18F-FDG PET/CT) uptake levels for KRAS mutation status and primary-metastatic tumor localization. METHODS: Our study is a retrospective cohort analysis that included RAS mutation status study and staging-oriented 18F-FDG PET/CT conducted on mCRC patients. RESULTS: There was no significant relationship between metastasis and primary tumor maximum Standardized uptake value (SUVmax) values according to the KRAS mutational status (P > 0.05). Patients with liver metastasis along with mutant BRAF mutation status had significantly higher SUVmax values in PET-CT scans (P = 0.04). There was a negative correlation between SUVmax values of lung metastases and overall survival (r = -0.35, P = 0.04). Patients with high carcinoembryonic antigen (CEA) levels had significantly higher SUVmax values of lung metastasis than patients with normal CEA levels (P = 0.009). Patients with high CA19-9 levels had significantly higher SUVmax values of liver, peritoneal, and bone metastasis than patients with normal CA19-9 levels (P = 0.002, P = 0.001, P = 0.004, respectively). There was no significant correlation between SUVmax values of metastasis and Lactate dehydrogenase (LDH) values. Liver metastasis of right-sided mCRCs had significantly higher SUVmax values (P = 0.03). CONCLUSION: We could not demonstrate a significant association between KRAS mutation and SUVmax values of PET scan in primary or metastatic tumor sites in advanced CRC.

Oxaliplatin­induced changes in splenic volume and liver fibrosis indices: retrospective analyses of colon cancer patients receiving adjuvant chemotherapy.

The aim of our study was to evaluate the association between increased splenic volume (SV) and liver fibrosis indices in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy. Patients who received adjuvant oxaliplatin-based regimens with the diagnosis of stage II and III colon cancer were evaluated. Splenic volume measurements, liver function tests, platelet count, and non-invasive liver fibrosis indices [NAFLD fibrosis score (NFS), AST to platelet ratio (APRI), and Fibrosis-4 (FIB-4)] were measured before and after treatment. A 30% increase in SV after chemotherapy compared to baseline was considered increased SV. The rate of increase in SV was 57.7% in the whole group. An increase in SV was shown at a higher rate in patients treated with capecitabine and oxaliplatin (CAPOX) than those treated with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (66.3% vs. 36.8%, p = 0.002). Furthermore, the CAPOX regimen (OR: 2.831, 95% CI: 1.125-7.121; p = 0.027), and higher post-treatment FIB-4 score (OR: 3.779; 95% CI:1.537- 9.294, p = 0.004) were determined as independent risk factors for the increased SV. Our study revealed that increased SV had a significant association with higher FIB-4 score in patients treated with oxaliplatin-based chemotherapy.

Retrospective Evaluation of the Efficacy of Gemcitabine-Based Therapies After FOLFIRINOX Failure in Advanced Pancreatic Cancer, Multi-Center Real-Life Data.

OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.

Cachexia index in predicting outcomes among patients receiving immune checkpoint inhibitor treatment for metastatic renal cell carcinoma.

INTRODUCTION: Immune checkpoint inhibitors (ICI) have transformed treatments for patients with metastatic renal cell carcinoma (mRCC). Although some patients benefit greatly from ICI treatments, an effective marker to determine which patients will benefit from these treatments is lacking. Moreover, chronic inflammation and sarcopenia have been associated with poor survival rates among cancer patients. Accordingly, in this study, we investigated how the cachexia index (CXI), used as a combined score for sarcopenia and chronic inflammation, affects the survival outcomes of patients with mRCC receiving ICI. METHODS: We retrospectively screened data from 52 mRCC patients who had followed up between October 2010 and October 2021 after receiving ICI as a second-line or later treatment. Patients' respective basal CXI score were calculated according to the following formula, based on their L3 vertebral skeletal musculoskeletal area (SMI), neutrophil-lymphocyte ratio (NLR), and albumin (Alb) levels: CXI = (SMI x Alb) / NLR. Additionally, we analyzed how patients' subcutaneous adipose tissue (SAT), body mass index (BMI), ECOG performance status, The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, nephrectomy status, sites of metastasis, and histological subtypes affected survival outcomes. RESULTS: Our univariate analysis significantly associated CXI score, NLR, nephrectomy status, and patient age with overall survival (OS). However, only CXI scores' significance was confirmed through multivariate analysis. The median OS (mOS) was 7 months for patients whose CXI score < the median value and 48 months for patients with a CXI score ≥ the median value. (HR 4.5, 95% CI [1.9-11], p = 0.001). Only CXI was significantly associated with progression-free survival (PFS) outcomes. The median progression-free survival (mPFS) was 4 months for patients whose CXI score < the median value and 17 months for patients with a CXI score ≥ the median value. (HR 2.6, 95% CI [1.3, 5.3], p = 0.007). Sarcopenia, sarcopenic obesity, and sarcopenia combined with NLR were not found to significantly affect OS. CONCLUSION: Our findings suggest that CXI score, a combined indicator of sarcopenia and chronic inflammation parameters, may serve as a useful marker in predicting the outcomes of ICI-based treatments for mRCC patients.

Thirty-day mortality rates after immunotherapy initiation.

Background: The aim of this study was to determine the cause of death in patients who died within 30 days after the first dose of immunotherapy. Methods: The data of 1432 patients treated with immunotherapy in six tertiary referral hospitals were retrospectively analyzed. Results: It was determined that 34 (2%) of the patients died within 30 days after the first dose of immunotherapy. Death occurred in all patients who received palliative therapy, and most patients (88%) received immunotherapy as second- or subsequent-line of therapy. The most common cause of death was disease progression and thromboembolic events. Conclusion: Preliminary results of the current study might give some clues to define the patient population in whom the fatal side effects of immunotherapy might be encountered.

Serum big endothelin-1 levels in female patients with breast cancer.

Endothelin-1[ET-1] acts as a growth factor in various malignancies. Big endothelin-1 (big ET-1) is the precursor of ET-1. The aim of this study was to determine the importance of serum big ET-1 levels as a novel marker of disease in female patients with breast cancer of various clinical stages. The study consisted of 75 female patients with breast cancer who were diagnosed and treated at the Gazi University Department of Medical Oncology and 20 controls. The patients were classified as follows: group A [n=26], patients with newly diagnosed primary breast cancer but without metastasis; group B [n=33], patients with metastatic breast cancer who had undergone treatment for their diseases and in whom metastasis was detected during follow-up; group C [n=16], off-therapy patients whose cancer had been in remission for at least 5 years; and group D [n=20] healthy controls. Serum big ET-1 level were measured with an enzyme immunoassay kit. The median serum big ET-1 levels of the 75 patients with breast cancer [10.96+/-1.36 ng/ml] were statistically significantly higher than those of controls [8.97+/-1.55 ng/ml]. The median serum big ET-1 levels of the patients with primary breast cancer patients [group A] were statistically significantly different from those in the controls, the off-therapy patients and the patients with metastatic disease [11.56+/-0.78 ng/ml, 8.97+/-1.55 ng/ml, 9.76+/-1.52 ng/ml, and 10.83+/-1.18 ng/ml respectively, P=.001]. There was no statistically significant difference in the serum big ET-1 levels of patients in group A in terms of tumor stage, hormone receptor status or lymph node status. Serum big ET-1 levels were statistically significantly higher in patients with metastatic disease than in controls or off-therapy patients (P=.001). The serum big ET-1 levels of off-therapy patients whose disease was in remission were not statistically significantly different from those in controls (P>.05). Serum big ET-1 levels seemed to represent the activation of ET-1 in female patients with breast cancer. Serum big ET- 1 levels can be an indicator of the breast cancer. Further studies are needed to demonstrate the prognostic importance of serum big ET-1 in patients with breast cancer.

Temozolomide in newly diagnosed malignant gliomas: administered concomitantly with radiotherapy, and thereafter as consolidation treatment.

BACKGROUND: Surgical resection followed by radiotherapy used to be the standard treatment in malignant gliomas. Recently, temozolomide has become a cornerstone in the treatment of these patients. We evaluated retrospectively the efficacy and the toxicity of temozolomide which was administered concomitantly with radiotherapy, and thereafter as consolidation treatment. PATIENTS AND METHODS: Medical records of 64 patients with malignant glioma were reviewed. Postoperatively, temozolomide was given at a dose of 75 mg/m(2)/day concomitantly with cranial radiotherapy. After 4 weeks of rest, patients were treated with temozolomide 200 mg/m(2) on days 1-5 every 28 days for 6 cycles. RESULTS: 62 patients were evaluable for response and toxicity. Objective response rate was 38.7% including 7 (11.3%) complete responses, and 17 (27.4%) partial responses. Median progression-free survival, and overall survival have not yet been reached in the grade III astrocytoma group at a median follow-up of 19 months. In the glioblastoma multiforme group, median progression-free survival, and median overall survival were 10 and 19 months, respectively. 2-year survival rates were 80% and 19% for the grade III astrocytoma, and for the glioblastoma multiforme groups, respectively. Toxicity was mild to moderate with rare grade 4 toxicities. CONCLUSION: Our data suggest that temozolomide is an active regimen for malignant gliomas. It was more effective in younger patients with better performance status.

Serum neopterin levels in patients with breast cancer.

The aim of this study was to determine the importance of serum neopterin level in female patients with breast cancer of various clinical stages. The study consisted of 75 female patients with breast cancer who were diagnosed and treated at the Gazi University Department of Medical Oncology. The patients were classified into three representative groups and a control group: group A (n = 26), patients with newly diagnosed primary breast cancer and without metastasis; group B (n = 33), patients with metastatic breast cancer who had undergone treatment for their diseases and on whom metastasis was detected during their follow-up; group C (n = 16), off-therapy patient whose cancer had been in remission for at least 5 years; group D (n = 20) healthy controls. The median serum neopterin levels of the 75 patients with breast cancer 11.0 (range, 0-23.6) nmol/L were significantly higher than those of controls (8.3 (range, 1.2-12.0) nmol/L). In group B patients, neopterin levels (12.6 (range, 0-23.6) nmol/L) were statistically significantly higher than those of controls, primary breast cancer patients, and off-therapy patients (P < .05). In group B, patients with visceral metastases had higher neopterin levels than did those with bone or local metastases; however, that difference was not statistically significant. The median serum neopterin levels of the primary breast cancer patients in group A (8.8 (range, 0-20) nmol/l) were not statistically significantly different from those in controls and off-therapy patients. Serum neopterin levels were significantly elevated in patients with metastatic breast cancer. Neopterin seems to be an indicator of metastatic cancer rather than a marker for local cancer. In patients with metastatic breast cancer, determining the serum neopterin levels may be useful in estimating survival; however, additional long-term follow-up will be needed.

Inhibitory effect of 5-fluorouracil on cytochrome P450 2C9 activity in cancer patients.

Drug interactions have been reported between 5-fluorouracil and cytochrome P450 2C9 (CYP2C9) substrates, S-warfarin and phenytoin. This study was performed to determine the influence of 5-fluorouracil on cytochrome P450 2C9 (CYP2C9) activity in colorectal cancer patients (n=17) receiving 5-fluorouracil. Losartan was used as a marker to assess CYP2C9 activity. Losartan and its CYP2C9 dependent metabolite, E-3174, were determined in urine. The ratios of urinary losartan/E-3174 before and after the 5-fluorouracil treatment were compared for each patient. Genotyping was performed to detect the CYP2C9*2 and CYP2C9*3. At the end of the first cycle of 5-fluorouracil, losartan/E-3174 ratio was increased by 28.0% compared to the pre-treatment values (P=0.15). In five patients recruited for phenotyping after three 5-fluorouracil cycles, the metabolic ratio was increased significantly by 5.3 times (P=0.03). The results suggest that in most patients 5-fluorouracil inhibited CYP2C9 activity. This inhibition was more pronounced when the total administered dose increased. This finding may help explain the mechanism of interaction between 5-fluorouracil and CYP2C9 substrates.

The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma.

AIMS AND BACKGROUND: p53, c-erbB-2 and Ki-67 protein expression and microvessel density (MVD) determined by CD34 antibody were evaluated by immunohistochemistry and their correlation with clinicopathological parameters including estrogen (ER) and progesterone (PR) receptor status and survival were investigated in patients with axillary lymph node-negative infiltrating ductal breast carcinoma. METHODS: The study population consisted of 47 patients with axillary lymph node-negative infiltrating ductal breast carcinoma. RESULTS: p53 and c-erbB-2 expression was detected in 36.2% and 31.9% of patients, respectively. Median Ki-67 expression was 10%. There were no statistically significant differences in the distribution of p53, Ki-67 and c-erbB-2 protein expression in relation to the age of the patients or to the size, histological grade or ER and PR status of the tumors. p53 protein expression correlated positively with c-erbB-2 and Ki-67 protein expression (P < 0.05). The mean MVD was 63.65 +/- 29.1 and it correlated positively with histological grade and Ki-67 expression (P < 0.05). Survival analysis revealed that age, tumor size, p53 and c-erbB-2 expression and PR status had no significant prognostic impact, whereas histological grade, proliferative activity and angiogenic activity were significant prognostic factors. Although ER-positive patients had a statistically significant overall survival advantage, the difference in disease-free survival was not significant. CONCLUSION: In axillary lymph node-negative breast carcinoma the histological grade and the proliferative and angiogenic activity of the tumor could be useful prognostic indicators.

Primary high grade malignant lymphoma of bladder.

Primary malignant lymphoma of bladder is one of the rarest extranodal site for lymphomas. Less than 100 cases have been reported so far. A history of chronic cystitis has been shown to be a preceding feature in many cases (40%) of primary bladder lymphoma. Most of the cases reported in the literature have a low-grade lymphoma including the subtypes of mucosa-associated lymphoid tissue. The diffuse large cell lymphoma is the most frequent type among the subtypes of high-grade bladder lymphomas. In this report, a case with high-grade primary malignant lymphoma of bladder is reported and the clinical, pathological aspects of diseases are reviewed.

Serum leptin levels are associated with tamoxifen-induced hepatic steatosis.

PURPOSE: Tamoxifen, used in breast cancer treatment, may induce hepatic steatosis. It has been suggested that leptin, which has a relationship with body fat stores, may be involved in the pathogenesis of hepatic steatosis. In this study, we compared serum leptin levels in tamoxifen-treated patients with and without hepatic steatosis. METHODS: Thirty-four women with breast cancer receiving tamoxifen were included in the study. Serum samples were obtained from the patients before and 3 months after tamoxifen therapy. RESULTS: Increased hepatic steatosis was detected in 15 of 34 (44%) patients after 3 months of tamoxifen therapy. Serum leptin levels were found to be significantly elevated in patients with increased hepatic steatosis (37.3 +/- 17.7 to 50.5 +/- 22.4 ng/ml, p = 0.023) compared to (48.2 +/- 20.2 to 42.6 +/- 14.9 ng/ml, p > 0.05) after tamoxifen treatment. CONCLUSION: Leptin may play a role in tamoxifen-induced hepatic steatosis. The exact mechanism involved should be investigated in further studies.

Serum interleukin-18 and nitric oxide activity in bladder carcinoma.

BACKGROUND: Both interleukin-18 and nitric oxide are multifunctional molecules that are involved in the different steps of carcinogenesis. METHODS: In the present study, we measured serum interleukin-18 and nitric oxide activity in 51 bladder cancer patients with different tumor stage and grade, and in 8 healthy controls. Serum nitrite-nitrate levels were measured as an index of nitric oxide generation. RESULTS: Serum interleukin-18 levels were significantly higher in bladder cancer patients when compared to the control subjects (p > 0.05). Serum interleukin-18 levels were found to be higher in patients with Ta stage than patients with T1 and T2, T3, T4 stages and in patients with grade 1 tumors than patients with grade 2 and grade 3 tumors, but this was not statistically significant (p > 0.05). There was no significant difference in serum nitrite + nitrate levels between bladder cancer patients and control subjects. CONCLUSIONS: Elevated serum interleukin-18 levels in bladder carcinoma patients may be a result of host defence mechanism against the growth and progression of bladder cancer cells.

Significance of serum vascular endothelial growth factor, insulin-like growth factor-I levels and nitric oxide activity in breast cancer patients.

Vascular endothelial growth factor (VEGF) is used to evaluate the angiogenic activity in breast carcinoma. Nitric oxide (NO) and insulin-like growth factor-I (IGF-I) are also implicated in breast tumorigenesis, including angiogenesis. We measured serum VEGF, IGF-I and nitrate+nitrite levels in 38 patients with metastatic and 23 with nonmetastatic breast cancer and in 16 controls. Serum VEGF and IGF-I levels were higher in patients with metastatic disease than in those with nonmetastatic disease or in controls (P<0.001). Serum nitrate+nitrite levels were higher in patients with metastatic and nonmetastatic disease than in controls (P<0.001). Patients with visceral metastasis and local metastasis had higher serum VEGF and nitrate+nitrite levels than patients with bone metastasis (P<0.05). In the metastatic disease group, there was a positive correlation between serum VEGF levels and nitrate+nitrite levels (r=0.436, P<0.05). Within the group with nonmetastatic disease, premenopausal patients had higher serum IGF-I levels than did postmenopausal patients (P<0.001). NO may involve an angiogenic process that is stimulated by VEGF in breast carcinoma. Larger studies are required to clarify these suggestions.

Prognostic implication of nm23-H1 expression in colorectal carcinomas.

AIMS: Expression of nm23 has been identified as a potential metastatic suppressor. In this study, nm23-H1 expression, clinicopathological parameters and influences on clinical outcomes were investigated in colorectal carcinoma patients. METHODS: Immunostaining was performed on 185 colorectal carcinomas using a polyclonal anti-nm23-H1 antibody. RESULTS: The nm23-H1 immunoreactivity was weak in 31 (17%), moderate in 48 (26%) and strong in 106 (57%) cases. The well differentiated adenocarcinomas showed significantly strong staining for nm23-H1 compared with the moderately and poorly differentiated adenocarcinomas (chi2 test, P<0.001). Advanced tumour stages were associated with reduced nm23-H1 expression (P<0.001). There was an inverse correlation with angiolymphatic invasion, nodal metastasis and liver metastasis (univariate logistic regression analysis, P<0.001). In univariate analysis, patients with reduced expression of nm23-H1 had significantly shorter overall and disease-free survival than the strong expression group (log-rank test for trend, P=0.002 and P=0.003, respectively). CONCLUSIONS: Our results indicated that reduced nm23-H1 expression showed poor prognosis in colorectal carcinomas. As a result, nm23-H1 expression might be a useful marker to predict outcome while planning treatment.

Expression of MUC1 and MUC2 mucins in gastric carcinomas: their relationship with clinicopathologic parameters and prognosis.

The aim of this study was to investigate the relationship between MUC1 and MUC2 mucin expressions and clinicopathologic variables in gastric carcinomas with regard to survival times. MUC1 and MUC2 expressions were revealed immunohistochemically in 143 gastric carcinomas. Of these 143 patients, follow-up data were available for 45 (median survival time of 30 months, ranging from 2 to 80 months). MUC1 was detected in 82 (58%), and MUC2 in 60 (42%) out of 143 cases. Papillary adenocarcinomas showed significantly higher MUC1 and MUC2 immunoreactivity than did signet-ring cell and mucinous tumors (p = 0.045 and p = 0.01, respectively). MUC1 was highly positive in intestinal-type carcinomas (p = 0.006), whereas intestinal and diffuse carcinomas did not differ in MUC2 expression. There was a positive correlation between tumor differentiation and MUC1 expression. However, no correlation was found between MUC1 and MUC2 expressions and angiolymphatic invasion. According to the TNM classification, stage 1A tumors have significantly lower rates of MUC1 reactivity compared to higher stages (p = 0.04). The patients with gastric carcinomas expressing MUC1 showed significantly poorer survival than those without MUC1 expression (p = 0.04). The present study suggests that MUC1 expression be a useful prognostic factor for predicting the outcome of gastric carcinoma patients, whereas the role of MUC2 expression is still unclear.