Prognostic importance of RASSF2 expression in patients with gastric cancer who had undergone radical gastrectomy

Background: Although Ras-association domain family of gene 2 (RASSF2) has been shown to undergo promoter methylation at high frequency in some cancer types and in brain metastases, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. Methods: Prognostic significance of RASSF2 expression was retrospectively analysed by immunohistochemically in 105 patients with gastric cancer who underwent curative gastrectomy. Results: Low RASSF2 expression was detected in 58 (55 %) patients, whereas 47 patients (45 %) had high RASSF2 expression. Lymph node involvement, pT stage, TNM stage, vascular invasion, perineural invasion and the presence of recurrence were found to be significantly related to RASSF2 expression levels. Low PRL-3 expression was closely correlated with lymph node metastasis (p = 0.001), advanced pT stage (p = 0.021), advanced TNM stage (p < 0.001), the presence of vascular invasion (p < 0.001), perineural invasion (p = 0.018) and high prevalence of recurrence (p = 0.003) compared with high RASSF2 expression. The median disease-free survival (DFS) time for patients with low RASSF2 expression was significantly worse than that of patients with high RASSF2 expression (10.2 vs. 50.6 months, p < 0.001). In addition, patients with high RASSF2 expression had the higher overall survival (OS) interval compared to patients with low RASSF2 expression (NR vs. 14.9 months, p < 0.001). In the multivariate analysis, the rate of RASSF2 expression levels was an independent prognostic factor, for DFS [p < 0.001, HR 0.12 (0.10-0.88)] and OS [p < 0.001, HR 0.10 (0.04-0.46)], as were pT stage and TNM stage, respectively. Conclusions: RASSF2 may be an important molecular marker for carcinogenesis, prognosis and progression in gastric cancer, but the potential value of RASSF2 expression as a useful molecular marker in gastric cancer progression should be evaluated, comprehensively. It would be possible to develop treatments targeting RASSF2 and advance new treatment strategies for gastric cancer

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The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients

Aim: The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens. Materials and methods: Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30-90 min every 21 days, and capecitabine was prescribed at 1000 mg/m2 twice daily on days 1-14 of the same 21-day schedule. Results: Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70-87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0-1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8-12.1) and the median OS was 25 months (95 % CI, 18.6-31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand–foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded. Conclusions: Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients (AU)

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Prognostic importance of RASSF2 expression in patients with gastric cancer who had undergone radical gastrectomy.

BACKGROUND: Although Ras-association domain family of gene 2 (RASSF2) has been shown to undergo promoter methylation at high frequency in some cancer types and in brain metastases, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. METHODS: Prognostic significance of RASSF2 expression was retrospectively analysed by immunohistochemically in 105 patients with gastric cancer who underwent curative gastrectomy. RESULTS: Low RASSF2 expression was detected in 58 (55 %) patients, whereas 47 patients (45 %) had high RASSF2 expression. Lymph node involvement, pT stage, TNM stage, vascular invasion, perineural invasion and the presence of recurrence were found to be significantly related to RASSF2 expression levels. Low PRL-3 expression was closely correlated with lymph node metastasis (p = 0.001), advanced pT stage (p = 0.021), advanced TNM stage (p < 0.001), the presence of vascular invasion (p < 0.001), perineural invasion (p = 0.018) and high prevalence of recurrence (p = 0.003) compared with high RASSF2 expression. The median disease-free survival (DFS) time for patients with low RASSF2 expression was significantly worse than that of patients with high RASSF2 expression (10.2 vs. 50.6 months, p < 0.001). In addition, patients with high RASSF2 expression had the higher overall survival (OS) interval compared to patients with low RASSF2 expression (NR vs. 14.9 months, p < 0.001). In the multivariate analysis, the rate of RASSF2 expression levels was an independent prognostic factor, for DFS [p < 0.001, HR 0.12 (0.10-0.88)] and OS [p < 0.001, HR 0.10 (0.04-0.46)], as were pT stage and TNM stage, respectively. CONCLUSIONS: RASSF2 may be an important molecular marker for carcinogenesis, prognosis and progression in gastric cancer, but the potential value of RASSF2 expression as a useful molecular marker in gastric cancer progression should be evaluated, comprehensively. It would be possible to develop treatments targeting RASSF2 and advance new treatment strategies for gastric cancer.

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients.

AIM: The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens. MATERIALS AND METHODS: Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30-90 min every 21 days, and capecitabine was prescribed at 1000 mg/m(2) twice daily on days 1-14 of the same 21-day schedule. RESULTS: Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70-87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0-1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8-12.1) and the median OS was 25 months (95 % CI, 18.6-31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand-foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded. CONCLUSIONS: Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients.

The differences of clinicopathological factors for breast cancer in respect to time of recurrence and effect on recurrence-free survival

Purpose. In the literature, small number of study has addressed time of recurrence in breast cancer. We analyzed clinicopathological factors predicting early or late recurrence in breast cancer patients and also prognostic factors related with recurrence-free survival (RFS) in recurrent patients. Patients/methods. We evaluated retrospectively 1980 breast cancer patients. Relapsed was defined as early if it was occured first 5 year of follow-up (Group 1) and late if it was occured after 5 years (Group 2). The clinicopathological factors were compared in respect of time of recurrence. The prognostic factors were evaluated using univariate and multivariate analyses. Results. Recurrence wase detected in 141 patient during follow-up. Tumors recurred after 5 years more likely to have lower stage (p = 0.05), tumors without lymphovascular invasion (LVI) (p < 0.001) and perineural invasion (PNI) (p = 0.01), and also HER2 negative (p < 0.001). The median RFS time and 5 years RFS rates were 42.9 months and 31.9 %, respectively. LVI (p = 0.01), PNI (p = 0.03), HER2 (p = 0.003), progesterone receptor (PR) (p = 0.04), the presence of neoadjuvant chemotherapy (p = 0.003), adjuvant hormonotherapy (p = 0.05) were found to be related with RFS. Axillary lymph node metastasis (p = 0.05) and the presence of PNI (p = 0.009) were poor prognostic factors for early recurrent group. PR-positive tumors (p = 0.001) and luminal subtypes (p = 0.03) had instances of late recurrences significantly. Conclusions. Clinicopathological factors predicting the recurrence time in breast cancer were important to modify adjuvant therapy (AU)

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Prognostic significance of ADAM17 expression in patients with gastric cancer who underwent curative gastrectomy

Backgrounds. A disintegrin and metalloproteinase (ADAM) 17 has been indicated to be an indispensable regulator of cellular events from proliferation to migration. Although prognostic importance of ADAM17 expression has been investigated in several tumours, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. In the current study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after curative gastrectomy. Methods. The prognostic significance of ADAM17 expression was analysed immunohistochemically in 156 patients with gastric cancer who had undergone curative gastrectomy, and the relationship between its expression and clinicopathological factors was also evaluated. Results. High ADAM17 expression was detected in 79 patients (51 %), whereas low expression was found in 77 cases (49 %). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression (p = 0.032). The median disease-free survival (DFS) time for patients with tumours with high ADAM17 expression was worse than that of patients with tumours with low ADAM17 expression (16.6 vs. 44.2 months, p = 0.004). In addition, patients with low ADAM17 expression had a higher median overall survival (OS) (49.6 vs. 26.9 months, p = 0.019) compared to those with high ADAM17 expression. Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to the already known important clinicopathological prognostic indicator. But the prognostic importance of ADAM17 expression could not be proved by multivariate analysis for OS. Conclusions. The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively; it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection (AU)

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The differences of clinicopathological factors for breast cancer in respect to time of recurrence and effect on recurrence-free survival.

PURPOSE: In the literature, small number of study has addressed time of recurrence in breast cancer. We analyzed clinicopathological factors predicting early or late recurrence in breast cancer patients and also prognostic factors related with recurrence-free survival (RFS) in recurrent patients. PATIENTS/METHODS: We evaluated retrospectively 1980 breast cancer patients. Relapsed was defined as early if it was occured first 5 year of follow-up (Group 1) and late if it was occured after 5 years (Group 2). The clinicopathological factors were compared in respect of time of recurrence. The prognostic factors were evaluated using univariate and multivariate analyses. RESULTS: Recurrence wase detected in 141 patient during follow-up. Tumors recurred after 5 years more likely to have lower stage (p = 0.05), tumors without lymphovascular invasion (LVI) (p < 0.001) and perineural invasion (PNI) (p = 0.01), and also HER2 negative (p < 0.001). The median RFS time and 5 years RFS rates were 42.9 months and 31.9 %, respectively. LVI (p = 0.01), PNI (p = 0.03), HER2 (p = 0.003), progesterone receptor (PR) (p = 0.04), the presence of neoadjuvant chemotherapy (p = 0.003), adjuvant hormonotherapy (p = 0.05) were found to be related with RFS. Axillary lymph node metastasis (p = 0.05) and the presence of PNI (p = 0.009) were poor prognostic factors for early recurrent group. PR-positive tumors (p = 0.001) and luminal subtypes (p = 0.03) had instances of late recurrences significantly. CONCLUSIONS: Clinicopathological factors predicting the recurrence time in breast cancer were important to modify adjuvant therapy.

Prognostic significance of ADAM17 expression in patients with gastric cancer who underwent curative gastrectomy.

BACKGROUNDS: A disintegrin and metalloproteinase (ADAM) 17 has been indicated to be an indispensable regulator of cellular events from proliferation to migration. Although prognostic importance of ADAM17 expression has been investigated in several tumours, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. In the current study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after curative gastrectomy. METHODS: The prognostic significance of ADAM17 expression was analysed immunohistochemically in 156 patients with gastric cancer who had undergone curative gastrectomy, and the relationship between its expression and clinicopathological factors was also evaluated. RESULTS: High ADAM17 expression was detected in 79 patients (51 %), whereas low expression was found in 77 cases (49 %). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression (p = 0.032). The median disease-free survival (DFS) time for patients with tumours with high ADAM17 expression was worse than that of patients with tumours with low ADAM17 expression (16.6 vs. 44.2 months, p = 0.004). In addition, patients with low ADAM17 expression had a higher median overall survival (OS) (49.6 vs. 26.9 months, p = 0.019) compared to those with high ADAM17 expression. Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to the already known important clinicopathological prognostic indicator. But the prognostic importance of ADAM17 expression could not be proved by multivariate analysis for OS. CONCLUSIONS: The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively; it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection.

Clinical importance of posphatase of regenerating liver-3 expression in breast cancer

BACKGROUND: Several biomarkers have been previously studied for breast cancer to define risk of recurrence and metastasis. Phosphatase of regenerating liver-3 (PRL-3) is one of them. High PRL-3 expression has been found to be correlated with axillary lymph node metastasis and survival in breast cancer. Herein, we evaluated the prognostic significance of PRL-3 expression and the relationship between PRL-3 and other clinicopathological factors. METHODS: PRL-3 expression was analyzed immunohistochemically in 122 invasive breast cancer tissues. We evaluated the correlation between PRL-3 and other clinicopathological factors by χ² test. Kaplan-Meier test and log rank method were used to define prognostic importance of PRL-3 expression. RESULTS: Of 122 breast cancer tumor samples, 46 (37.7 %) were negative while 76 (62.3 %) were positive in respect to PRL-3 expression. There was significant correlation between PRL-3 expression and other clinicopathological factors, such as histology, lymphovascular invasion (LVI), necrosis, progesterone receptor (PR) status, and the presence of triple negative disease. Tumors with LVI and necrosis had more positive PRL-3 expression compared to tumors without LVI or necrosis (P = 0.05 and 0.03, respectively). Triple negative and cerb-B overexpressed breast cancers were found to be more positive PRL-3 expression than hormone receptor positive with cerb-B negative groups (luminal A) (P = 0.02).We could not find any relationship between PRL-3 expression and overall survival (OS) or disease-free survival (DFS) (P > 0.05). CONCLUSION: Although PRL-3 expression was related to LVI or necrosis which is important for tumor invasiveness, we could not find that PRL-3 as an important prognostic factor in breast cancer patients. In addition, triple negative and cerb-B overexpressed tumors, which had worse prognosis compared to hormone receptor positive without cerb-B expressed group, associated with also PRL-3 positivity more than PRL-3 negative group (AU)

Efficacy, safety and prognostic features of resected colon carcinoma treated in "real world" practice: a retrospective cohort-study.

PURPOSE: Treatment outcomes and prognostic features of a specific cancer generally come from prospective randomized studies. It seems reasonable to ask the question whether the results of prospective randomized studies entirely reflect the results of the population treated in "real world" practice. Therefore we performed a retrospective cohort analysis in order to find out the efficacy of adjuvant chemotherapy as well as the prognostic factors of our patient population treated in daily practice, and compared these findings with those defined in the prospective studies. METHODS: Data of patients with high risk stage II and all stage III colon cancers treated with adjuvant chemotherapy were retrospectively analyzed. RESULTS: A total of 190 patients were retrospectively analyzed. The rates of T2, T3, and T4 tumors were 4.2, 77.9, and 17.9%, respectively. Over 35% of the patients had stage II disease. Of the 5- fluorouracil (5-FU)-based chemotherapy group (n=141), 15% had a dose reduction because of toxicity and 73% were given the total planned dose and cycles, whereas these rates were 18.5 and 66% for oxaliplatin+5-FU treated group, respectively (p=0.66 and 0.44, respectively). The 3-year disease-free survival (DFS) and 5-year cancer-specific overall survival (OS) for all patients were 69.4 and 73%, respectively. In multivariate analysis, cancer-specific OS showed significant correlation with T stage (p=0.015) and with perineural invasion (p=0.024). Also patients ≥ 65 years old had significantly lower OS (p= 0.003) CONCLUSION: This study is the fi rst to report the efficacy of adjuvant treatment in a curatively resected Turkish colon carcinoma population treated in "real world" practice. Our study showed that the treatment results and the prognostic parameters of Turkish colon carcinoma patients treated in "real world" practice are not different from those of selected patients treated in randomized prospective studies.

ERCC1 is not expressed in hepatocellular cancer: A turkish oncology group, gastrointestinal oncology subgroup study.

PURPOSE: hepatocellular cancer (HCC) is a common malignancy with a high mortality rate. Existence of excisional repair cross complementation1 (ERCC1) is implicated in resistance to cisplatin treatment. Expression of ERCC1 in HCC is not known. In this study we aimed to find out whether a subset of HCC patients can be identified to benefit from cisplatin. METHODS: sixty-one patients with HCC who had enough tissue to do immunohistochemistry were identified in 3 institutions. Immunohistochemical staining was performed manually using the standard streptavidin-biotin-peroxidase method. Monoclonal anti-ERCC 1 (D-10) antibody from Santa Cruz Biotechnology (Santa Cruz, CA) was used. RESULTS: only one out of 61 patients (1.6%) had ERCC1 expression. CONCLUSION: although around 10% of HCC patients respond to cisplatin, this is unlikely to be due to ERCC1 negativity. Pathways other than ERCC1 should be searched to find ways to help these patients' treatment strategies.

Safety and efficacy of transdermal fentanyl in patients with cancer pain: phase IV, Turkish oncology group trial.

We have performed a prospective evaluation of the efficacy, safety and convenience of the transdermal therapeutic system - fentanyl (TTS-F) in Turkish cancer patients when it was newly available in Turkey. Ninety-nine patients with historically confirmed malignancy and pain entered the study; the mean age was 55.1 (16-58) years. The study duration was 28 days. Transdermal therapeutic system - fentanyl was used in opioid-naïve or pre-treated patients. Most patients reported a decrease in pain severity. Use of rescue medication decreased from day 4 to day 28. The majority of patients rated patch convenience of use as excellent. A total of 22.2% of patients experienced adverse events that were either probably related or very likely to be related to the study drug. The majority of the adverse events mentioned were related to the digestive system. Eighteen serious adverse events were reported by 13 patients. Six events were doubtfully related, and 12 events were not related to the study drug. Four patients died during the trial. None of these deaths was attributed to the study drug. In conclusion, the trial showed that TTS-F is easily managed, effective and will help to enable the appropriate opioid administration to patients who are suffering from cancer pain in Turkey.

HPV DNA frequency and subset analysis in human breast cancer patients' normal and tumoral tissue samples.

Viruses are known to be associated with human malignancies, e.g., Epstein-Barr virus, human papillomavirus (HPV) and human T-cell leukemia virus type I. We conducted a prospective study to define the role of HPV in breast cancer. The malignant and normal breast tissue samples of 50 consecutive breast cancer patients were obtained postoperatively. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Thirty-seven samples (74%) of tumoral breast tissue expressed HPV-DNA, 16 normal breast tissue samples (32%) were positive as well. There was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples. HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (54.4%) and in 9 of the HPV-DNA positive normal tissue (56.3%). HPV-33 also was detected in 35 (94.6 %) of the HPV-DNA positive tumoral tissue and in 14 (87.5 %) of the HPV-DNA positive normal tissue samples. HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Additional studies looking at HPV and HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer.

Neoplastic diseases prevalence in a turkish university hospital.

PURPOSE: The purpose of this study was to register the different cancer cases diagnosed in our hospital with an aim to define the most common and treatable cancer types and help define accurate targets for the allocation of the already limited resources of the Ministry of Health. MATERIALS AND METHODS: We surveyed 12 months of the hospital's pathology records to determine the prevalence of various cancer types. RESULTS: Out of 9720 biopsy and cytology samples, 662 were cancer cases. Breast and gastric cancers were higher and colorectal cancers were lower than the series reported from the United States. Of the pulmonary malignancies, lung cancer in general was not particularly higher in proportion to other cases, something interesting for a country with smoking rates exceeding 60% of the adult population. Squamous cell lung cancer was more common compared to the rates reported in the western world statistics. CONCLUSION: Although biases may exist, as certain cancers are more amenable to surgical intervention and physician groups may have special interest toward a particular cancer, distribution of cancer cases in Turkey is probably similar to the western world.