Immunohistochemical expression of human epidermal growth factor receptor (HER)-4 and prognosis in patients with metastatic breast cancer.

PURPOSE: The clinical value of HER4 - a cell surface receptor that belongs to the human epidermal growth factor receptor family - for predicting survival outcomes in patients with breast cancer remains controversial. Herein, we sought to investigate the prognostic significance of HER4 immunohistochemical expression with respect to progression-free survival (PFS) and overall survival (OS) in Turkish patients with metastatic breast cancer (MBC). METHODS: MBC patients (N=45; mean age=50.5±12.7 years) were consecutively enrolled between 2000 and 2006 in the Department of Oncology at the Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections. The predictive value of HER4 expression was investigated by multivariate analysis after allowance for potential confounders. RESULTS: The mean PFS in the study participants was 11.35 months (range:1-50), whereas the median OS was 22.18 months (range:1-76). The mean PFS in patients with a HER4 immunohistochemical score of 0, 1+, 2+, and 3+ was 11.0 ± 4.8, 11.3 ± 7.7, 11.7 ± 8.1, and 10.4 ± 7.4 months, respectively (p=0.99) . The mean OS in patients with a HER4 score of 0, 1+, 2+, and 3+ was 13.3 ± 6.8, 25.6 ± 10.8, 22.9 ± 10.7, and 13.5 ± 9.9, months, respectively (p=0.44). The results of multivariate Cox regression analysis indicated that the presence of visceral metastases was the only independent prognostic factor for both OS (HR=3.01, 95% CI=1.56-3.99, p <0.01) and PFS (HR=2.91, 95% CI=1.51-3.78, p <0.01). CONCLUSION: HER4 immunohistochemical expression is not an independent predictor of OS and PFS in Turkish MBC patients.

Prognostic impact of tumor lymphocytic infiltrates in patients with breast cancer undergoing neoadjuvant chemotherapy.

PURPOSE: The presence of a pronounced tumor lymphocytic infiltrate (TLI) is deemed to reflect the presence of an immunoinflammatory response against the tumor and may thus have prognostic significance. We investigated the prognostic value of TLI detected in pathological specimens collected following neoadjuvant chemotherapy (NACT) in patients with breast cancer. METHODS: 100 consecutive patients with breast cancer (mean age 47.8±11.4 years) who were scheduled to undergo anthracycline-and/or taxane-containing NACT were enrolled. Specimens collected after NACT were scored with the 4-point Klintrup scoring criteria for the presence of TLI. RESULTS: 60 patients had low-grade TLI and 40 high-grade TLI. Comparison of the patient population according to low-grade vs high-grade TLI revealed statistically significant difference both in terms of disease-free survival (DFS) (log rank-4.28, p<0.05) and overall survival (OS) (log rank=3.96, p<0.05), with high-grade TLI patients showing a better prognosis. Multivariate Cox regression analysis identified postoperative tumor size and low-grade TLI as the two main independent adverse prognostic factors. CONCLUSION: High-grade TLI may interfer with tumor growth and can represent a favorable prognostic factor in women with breast cancer undergoing NACT.

Neoadjuvant chemotherapy-induced changes in immunohistochemical expression of estrogen receptor, progesterone receptor, HER2, and Ki-67 in patients with breast cancer.

PURPOSE: The impact of neoadjuvant chemotherapy (NACT) on immunohistochemical markers in breast cancer specimens remains controversial. We designed the current study to investigate the potential changes in estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 expression before and after NACT in a cohort of Turkish patients with breast cancer. METHODS: This research was designed as a prospective, observational study of 100 consecutive patients with breast cancer (mean age 47.8±11.4 years) who were scheduled to undergo anthracycline- and/or taxane-containing NACT before attempting cytoreductive surgery at the Department of Oncology of the Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded specimens. RESULTS: Changes in immunohistochemical markers before and after NACT were only significant for HER-2 and Ki- 67. More specifically, the number of HER-2-positive specimens decreased from 21 before NACT to 8 after NACT (p<0.001). Similarly, the number of tumor samples positive for Ki-67 decreased significantly from 65 to 24 after NACT (p<0.001). Mean pre- and post-treatment tumor grades of differentiation before and after NACT were 2.56 ± 0.67 and 2.37±1.07, respectively (p<0.05). We did not find any significant associations between baseline ER, PR, HER2, and Ki-67 expression with both overall survival (OS) and disease- free survival (DFS). CONCLUSION: Our study suggests that NACT reduces the expression of HER2 and Ki-67 in breast cancer specimens. The significance of NACT-induced changes in the immunohistochemical expression of HER2 and Ki-67 in patients with breast cancer should be further studied in future translational and clinical research.

Pulmonary actinomycosis mimicking metastasis from lung adenocarcinoma.

BACKGROUND: Pulmonary actinomycosis may create a diagnostic and therapeutic dilemma especially in cancer patients. CASE REPORT: A 64-year-old male patient presented with a productive cough, bloody sputum, and weight loss. Thoracic computed tomography (CT) showed a 5-cm mass in the upper lobe of the right lung, and a 2-cm mass in the lower lobe of the left lung. Bronchoscopic examination did not show any endobronchial lesions. CT-guided needle biopsy of the right pulmonary lesion showed lung adenocarcinoma. Wholebody positron emission tomography/CT revealed an increase in fluorodeoxyglucose accumulation in the upper lobe of the right lung, in the lower lobe of the left lung, and in the right hilar and paratracheal lymph nodes. Before chemotherapy was initiated, the patient had to be admitted to the hospital because of massive hemoptysis. Bronchoscopic examination indicated persistent bleeding in the left lower lobe bronchus. The patient underwent diagnostic left thoracotomy, and wedge resection of the lower lobe mass. The diagnosis was pulmonary actinomycosis, and the patient received oral amoxicillin. He underwent successful surgery for the primary disease following 6 cycles of chemotherapy. CONCLUSION: Oncologists should be aware of rare diseases that may affect management approaches in the treatment of cancer.

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer.

BACKGROUND/AIMS: 5-Fluorouracil-based chemoradiotherapy is the most widely used treatment modality in the adjuvant treatment of rectal cancer. Capecitabine represents a valuable alternative to 5-Fluorouracil in this situation. METHODOLOGY: Patients with stage II and stage III rectal adenocarcinoma, who were included in this analysis, received adjuvant chemoradiotherapy consisting of external-beam radiotherapy (50.4-54Gy) either with 5-Fluorouracil at a median dose of 300 mg/m2/day by protracted venous infusion for 5 days a week, or capecitabine at a median dose of 1650 mg/m2/day for 5 days a week after surgery. The data concerning the toxicity and the efficacy of the treatments were compared in patients treated with 5-Fluorouracil- and capecitabine-based chemoradiotherapy. RESULTS: Forty-three patients received 5-Fluorouracil, and 24 patients received capecitabine during adjuvant radiotherapy. Although there were no differences between the groups in terms of toxicity rates, distant metastasis-free survival, disease-free survival, and overall survival rates; a trend for improved loco-regional recurrence-free survival rate was observed in the capecitabine arm (p = 0.063). CONCLUSIONS: Capecitabine is at least as effective as 5-Fluorouracil in the postoperative treatment of rectal adenocarcinoma. Considering the trend for improved loco-regional recurrence-free survival rate in the capecitabine arm, it seems that the drug exerts better synergy with radiotherapy in this situation.

Fatal ischemic bowel necrosis possibly due to docetaxel and cisplatin in a patient with non-small cell lung cancer.

We would like to report fatal ischemic bowel necrosis (IBN) as an unexpected complication of docetaxel and cisplatin in a patient with non-small cell lung cancer.

Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer.

AIMS AND BACKGROUND: To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. RESULTS: After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). CONCLUSIONS: The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incorporation of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

Spectrum of EGFR gene mutations and ALK rearrangements in lung cancer patients in Turkey.

The EGFR gene and ALK rearrangements are two genetic drivers of non-small cell lung cancer (NSCLC). The frequency of EGFR mutations and ALK rearrangement varies according to not only ethnicity but also gender, smoking status and the histological type of NSCLC. In the present study, we demonstrated the distribution of EGFR mutations in 132 NSCLC patients by using a pyrosequencing technique and the distribution of ALK rearrangements in 51 NSCLC patients by using fluorescent in situ hybridization technique in Turkey. Additionally, we compared the clinicopathological data of NSCLC patients with the mutation status of EGFR in their cancerous tissues. Both EGFR mutations and ALK rearrangements were identified in 19 (14.39 %) and 1 (1.96 %) patients, respectively. We found EGFR mutations in codon 861, 719 and 858 with the ratios of 10.52 % (2/19), 10.52 % (2/19) and 31.58 % (6/19), respectively, and deletion of exon 19 in 47.37 % (9/19) of the patients. We found the frequency of EGFR mutations to be significantly higher in female patients and nonsmokers (p = 0.043, p = 0.027, respectively). Consequently, we found EGFR mutations to be more frequent in female patients and nonsmokers. Future studies on larger patient groups would provide more accurate data to exhibit the relationship between EGFR mutations and ALK rearrangements and the clinicopathological status.

The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases.

BACKGROUND: Although bone marrow metastases can be found commonly in some malignant tumors, diagnosing a nonhematologic malignancy from marrow is not a usual event. METHODS: To underscore the value of bone marrow aspiration and biopsy as a short cut in establishing a diagnosis for disseminated tumors, we reviewed 19 patients with nonhematologic malignancies who initially had diagnosis from bone marrow. RESULTS: The main indications for bone marrow examination were microangiopathic hemolytic anemia (MAHA), leukoerythroblastosis (LEB) and unexplained cytopenias. Bone marrow aspiration was not diagnostic due to dry tap or inadequate material in 6 cases. Biopsy results were parallel to the cytological ones in all cases except one; however a meticulous second examination of the biopsy confirmed the cytologic diagnosis in this patient too. The most common histologic subtype was adenocarcinoma, and after all the clinical and laboratory evaluations, the primary focus was disclosed definitively in ten patients (5 stomach, 3 prostate, 1 lung, 1 muscle) and probably in four patients (3 gastrointestinal tract, 1 lung). All work up failed in five patients and these cases were classified as tumor of unknown origin (TUO). CONCLUSION: Our series showed that anemia, thrombocytopenia, elevated red cell distribution width (RDW) and hypoproteinemia formed a uniform tetrad in patients with disseminated tumors that were diagnosed via bone marrow examination. The prognosis of patients was very poor and survivals were only a few days or weeks (except for 4 patients whose survivals were longer). We concluded that MAHA, LEB and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Because of the very short survival of many patients, all investigational procedures should be judged in view of their rationality, and should be focused on treatable primary tumors.

Association and Prognostic Significance of the Functional -1562C/T Polymorphism in the Promoter Region of MMP-9 in Turkish Patients with Gastric Cancer.

Matrix metalloproteinases (MMPs) are a group of zinc-dependent peptidases that participate in matrix turnover in solid malignancies. The aim of this study was twofold. First, we sought to investigate under a case-control design the association between the functional -1562C/T polymorphism in the promoter region of MMP-9 and gastric cancer (GC) in a Turkish sample. Second, we examined its prognostic significance in GC patients. A total of 144 subjects were enrolled in the case-control study (79 GC cases and 65 controls). Overall survival (OS) and progression-free survival (PFS) served as the main outcome measures in the longitudinal study. The MMP-9 -1562C/T polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The odds ratio (OR) of GC for the CC genotype relative to the CT+TT genotypes was not significant (OR = 0.89, 95 % confidence interval [CI] = 0.44-1.82, P = 0.75). These results did not change after allowance for age and sex in multivariable regression analysis (OR = 0.81, 95 % CI = 0.40-1.94, P = 0.84). When the MMP-9 -1562C/T polymorphism was analyzed among GC patients in relation to OS and PFS, we found no significant differences between subjects with the CC and CT+TT genotypes. In conclusion, the results of our study did not point toward a major role of the MMP-9 -1562C/T polymorphism in the pathogenesis and clinical course of GC in Turkish subjects.

Prognostic value of nm23 in gastrointestinal stromal tumors.

AIM/BACKGROUND: nm23 is suggested to represent a new class of metastasis suppressor genes. An inverse correlation between nm23 expression level and metastatic potential has been demonstrated in different malignancies. This study evaluated the prognostic value of nm23 in gastrointestinal stromal tumors (GISTs). METHODS: Immunohistochemical expression level of nm23 was studied in a total of 32 patients with localized GISTs. The relationship between the expression level of nm23 and patient outcome was investigated. RESULTS: A tumor size of 10 cm or more and a mitotic rate of 10 or more per 50 high-power fields were not significantly associated with the metastasis risk (p = 0.60 and 0.55, respectively). Tumors with high expression of nm23 tended to have significantly lower metastatic potential (p = 0.02). The median survival was significantly longer in patients with high expression of nm23 (p = 0.007). CONCLUSION: These results suggest that expression level of nm23 may be considered as a prognostic predictor in GISTs. Future studies with larger patient numbers will be essential to confirm the prognostic significance of nm23 in patients with GIST.

Protective effect of amifostine against toxicity of paclitaxel and carboplatin in non-small cell lung cancer: a single center randomized study.

AIM: In this study we determined the protective role of amifostine against the side effects of the combination of paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemo-naive patients with NSCLC were eligible. Thirty-eight patients were randomized to receive paclitaxel 175 mg/m2 and carboplatin AUC = 6 with amifostine 910 mg/m2 (group B) or chemotherapy alone (group A). The occurrences of hematologic, neurologic, cardiologic toxicities, and ototoxicity were evaluated. RESULTS: All patients completed the six scheduled cycles of therapy. A total of 114 cycles of chemotherapy was given in both groups. Neutropenia grade 3-4 was observed in 11 cycles (9.6%) in group A and 19 cycles (16.6%) in group B (p = 0.16). Paresthesia grade 1 or 2 was observed in 18 of 19 patients of group A and in 8 of 19 patients of group B, following the sixth cycle of chemotherapy (p = 0.018). Two patients of group B and nine patients of group A suffered from sensory motor impairment grade 2 (p = 0.029). There was no clinical evidence in any patient for deterioration in cardiac function. Asymptomatic and transient sinus bradycardia or ventricular premature beats developed in four patients. None of the patients reported vertigo, tinnitus, or hearing loss. CONCLUSION: The addition of the amifostine to the combination of paclitaxel and carboplatin may prevent or reduce the incidence of neurotoxicity in the treatment of NSCLC. Amifostine does not appear to have a preventive role in neutropenia.

Evaluation of the effects of Helicobacter pylori eradication therapy on gastric antral epithelial hyperproliferation: a prospective six-month follow-up study.

BACKGROUND/AIMS: H. pylori-induced hyperproliferation of the gastric epithelium may have a critical role in gastric carcinogenesis. H. pylori-related hyperproliferation and reversibility of hyperproliferation after eradication therapy is still controversial. Therefore, we have evaluated the effects of H. pylori and its eradication on gastric antral epithelial proliferation. METHODOLOGY: A total of 32 H. pylori-positive and 22 H. pylori-negative subjects were enrolled into the study. Triple eradication therapy was given to the H. pylori-positive group. Upper endoscopy was repeated one month after the therapy and six months later, antral biopsy specimens were taken in each endoscopy. Biopsy specimens from H. pylori-negative subject were taken at the beginning of the study and sixth months later also. RESULTS: Proliferative index was 40.2% in H. pylori-positive state; it regressed to 27.6% after eradication and six months later the proliferative index was 30.7%. H. pylori-negative group's proliferative index was 25.5% initially and six months later it was 25.6%. The difference between the H. pylori-positive and -negative group was statistically significant (p<0.0001). The difference between H. pylori-positive group's values at the beginning of the study and one month after the eradication was significant (p<0.0001). In addition, the difference between H. pylori-positive group's initial values and those six months after eradication was also significant (p<0.0001). CONCLUSIONS: H. pylori increased the gastric epithelial proliferation and after the eradication therapy proliferative index decreased to control values. H. pylori and the related factors inducing gastric antral hyperproliferation may have an important role in H. pylori-related gastric malignancies.

Comparison of clinical outcomes of different erythropoietin usage strategies.

AIM: There is no comprehensive study that compares the different usage strategies of recombinant human erythropoietin (rHuEPO) in platinum-induced anemia. In order to clarify this issue, we conducted a prospective clinical study. MATERIAL AND METHODS: Seventy-seven patients were studied in three main groups. Group 1 (n = 17) consisted of cancer patients without anemia. These patients received rHuEPO starting from the first chemotherapy cycle. Group 2 (n = 26) consisted of patients whose hemoglobin (Hb) values decreased by at least 1 g/dL after the first cycle of chemotherapy. Group 3 (n = 34) consisted of patients whose Hb values dropped below 10.5 g/dL after the second chemotherapy cycle. Groups 2 and 3 were each divided into two subgroups. In groups 1, 2A and 3A rHuEPO (5000 U/day subcutaneously three times a week) treatment was continued until three weeks after the completion of chemotherapy. In groups 2B and 3B, rHuEPO was given for 12 weeks only. RESULTS: There were no prominent differences between the Hb values of these groups throughout the chemotherapy cycles. Transfusion rates and the number of patients who became anemic were also not different between groups. CONCLUSION: No rHuEPO usage strategies are superior to others in terms of Hb levels and transfusion requirements. The decision as to when rHuEPO is to be added to platinum-containing therapy should be tailored to the health conditions of individual patients.

Treatment of metastatic pancreatic cancer with a combination of gemcitabine and 5-fluorouracil: a single center phase II study.

AIM: To determine the activity and toxicity of a combination of weekly gemcitabine and 5-fluorouracil bolus intravenously in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Twenty-one patients with previously untreated metastatic pancreatic cancer were included in this phase II study. The schedule was gemcitabine (1000 mg/m2 i.v.) and 5-fluorouracil (500 mg/m2 bolus i.v.) weekly for 3 weeks every month. RESULTS: Four patients (19%) achieved a partial response and three stable disease. A clinical benefit was obtained in 7 patients (33%). Median survival for all the patients was 6 months. The treatment was well tolerated and toxicity was mild. WHO grade 3 leukopenia occurred in 2 (9.5%) patients, grade 3 anemia in 4 (19%) patients, grade 3-4 thrombocytopenia in 4 (19%) patients, grade 1 diarrhea in 1 (4.7%) patient and grade 1 mucositis in 3 (14.2%) patients. CONCLUSION: The weekly administration of gemcitabine combined with 5-fluorouracil bolus i.v. is an active and well-tolerated regimen in metastatic pancreatic cancer. However, its efficacy is relatively limited.

Single-agent irinotecan as second-line treatment for advanced gastric cancer.

AIM: To investigate the activity and toxicity of irinotecan (CPT-11) as a single agent in patients with advanced gastric cancer after failure of previous 5-fluorouracil-based combination chemotherapy. PATIENTS AND METHODS: Sixteen patients with advanced gastric received CPT-11, 350 mg/m2 every 21 days. The median age of the patients was 54.6 years; ECOG performance status was 0-1 in 14 patients and 2 in 2 patients. Dominant metastatic sites included liver, lung, lymph nodes and peritoneum. RESULTS: No complete response was observed. Two patients (12.5%) achieved a partial response to treatment. One patient (6.25%) had a minor response. Ten patients (62.5%) had progressive disease on therapy, and 3 patients (18.75%) had stable disease. The median survival of all 16 patients was 5 months. Grade 3 neutropenia was observed in 3 patients (18.75%), grade 4 thrombocytopenia in 1 patient (6.25%), and grade 3 anemia in 1 patient (6.25%). Three patients (18.75%) suffered from grade 3 diarrhea. CONCLUSIONS: CPT-11 is moderately active and a well-tolerated regimen for selected advanced gastric cancer patients who experience disease progression after receiving first-line treatment.

Small cell carcinoma of the urinary bladder. A clinicopathologic study of five cases.

AIMS AND BACKGROUND: Small cell carcinoma of the bladder (SCCB) is a rare entity characterized clinically by an aggressive behavior with a high incidence of systemic metastases. We report the clinicopathologic findings of five cases. METHODS: We reviewed five consecutive patients with SCCB treated at our institute. In each case the following clinical data were recorded: age, sex, presenting symptoms, endoscopically determined location of the tumor, clinical staging, node involvement (if any), site of metastases (if any), treatment, follow-up and outcome. RESULTS: There were four male and one female patients, age range 42 to 68 years, mean 57.6 years. The clinical presentation was not different from conventional transitional cell carcinoma, with hematuria being the most frequent complaint (four cases). Microscopic examination revealed oat cells in three cases and an intermediate variant in one. At the time of diagnosis the tumors were staged as T3bN2M0, T2N2M0, T4N0M0, T3aN0M0, and T2N0M0. Primary therapy consisted of radical cystectomy alone (one case), transurethral resection (TUR) alone (one case), TUR with chemotherapy (two cases), or TUR with chemotherapy and radiotherapy (one case). Four patients died of progressive disease, with survival from the time of diagnosis ranging from 7 to 16 months (mean, 12.2 months). One patient died of myocardial infarction (unrelated to the primary disease) one month after diagnosis. CONCLUSION: Our study indicates that primary small cell carcinoma of the urinary bladder is as aggressive as its pulmonary counterpart and the overall prognosis of this tumor is very poor.

Molecular markers for patients with thymic malignancies: not feasible at present?

BACKGROUND: Thymomas and thymic carcinomas are rare malignancies and devising clinically effective molecular targeted therapies is a major clinical challenge. The aim of the study was to analyze BLC2 and vascular endothelial growth factor receptor (VEGFR) expression and KRAS and EGFR mutational status and to correlate them with the clinical characteristics of patients with thymomas and thymic carcinomas. MATERIALS AND METHODS: A total of 62 patients (mean age: 50.4 ± 13.2 years) with thymomas and thymic carcinomas were enrolled. The expression of BLC2 and VEGFR in tumor cells and normal tissues was evaluated by RT-PCR. The mutational status of the KRAS and EGFR genes was investigated by PCR with sequence specific primers. RESULTS: The BLC2 and VEGFR expression levels did not differ significantly between tumor and normal tissues. Moreover, there were no clearly pathogenic mutations in KRAS or EGFR genes in any tumor. None of the molecular markers were significantly related to clinical outcomes. CONCLUSIONS: Changes in levels of expression of BLC2 and VEGFR do not appear to be involved in thymic tumorigenesis. Moreover, our data suggest that KRAS and EGFR mutations do not play a major role in the pathogenesis of thymomas and thymic carcinomas.

Prognostic significance of c-erbB2 overexpression in patients with metastatic gastric cancer.

BACKGROUND: Overexpression of the gene c-erbB2, which encodes a receptor tyrosine kinase, has been associated with prognosis and response to therapy in several solid tumors. This study was designed to test whether c-erb-B2 overexpression can be related to prognosis of patients with metastatic gastric cancer. METHODS: Between 2005 and 2010, 46 cases of metastatic gastric cancer were evaluated immunohistochemically for c-erb-B2 overexpression. Overall survival (OS) and time-to-progression (TTP) served as the main outcome measures. RESULTS: c-erbB2 was overexpressed in 19 (41.3 %) cases and 8 patients (17.4 %) had a c-erbB2 score of 3+ (a strong complete membrane staining observed in >10 % of the tumor cells). c-erbB2 expression was not associated with the clinicohistological characteristics of the study participants. The mean OS was 11.48 ± 1.03 months, whereas the mean TTP was 8.28 ± 0.8 months. Compared with patients with a score of 2+ or less (n = 38), those with a c-erbB2 score of 3+ (n = 8) had both a significantly lower OS (15.55 ± 1.63 vs. 8.22 ± 0.88 months, respectively, p < 0.05) and TTP (10.72 ± 1.81 vs. 6.11 ± 0.61 months, respectively, p < 0.05). After allowance for potential confounders, Cox regression analysis identified a c-erbB2 score of 3+ as an independent predictor of both OS (hazard ratio = 1.9; 95 % confidence interval = 1.1-3.7, p < 0.05) and TTP (hazard ratio = 1.8; 95 % confidence interval = 1.1-4.1, p < 0.05). CONCLUSION: Our results suggest that c-erbB-2 overexpression may have a prognostic significance in patients with metastatic gastric cancer.

The SOCS-1 -1478CA/del polymorphism is not associated with colorectal cancer or age at onset in Turkish subjects.

BACKGROUND: Suppressor of cytokine signaling (SOCS)-1 acts as a key regulator of many cytokine signaling pathways and its abnormal expression has been identified in several human malignancies, suggesting potential roles in carcinogenesis. The aim of this study was to investigate any association between the functional SOCS- 1 -1478CA>del polymorphism and colorectal cancer (CC) as well as age at onset in a Turkish clinical sample. MATERIALS AND METHODS: A total of 122 subjects were enrolled in this case-control study (70 CC cases and 52 controls). The SOCS-1 -1478CA>del polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The odds ratio of the del allele for CC relative to the CA allele was not significantly different between the groups (OR=0.71, 95% CI=0.41-1.22, p=0.27). This result did not change after adjustment for age and sex on multivariable regression analysis (OR=0.84, 95% CI=0.59-1.34, p=0.53). When the SOCS-1 -1478CA>del polymorphism was analyzed among CC patients in relation to the age at disease onset, we found no significant differences between subjects with the del/del, CA/del, and CA/CA genotypes. CONCLUSIONS: The results of our study did not point towards a major role of the SOCS-1 -1478CA>del polymorphism in the pathogenesis of CC in Turkish subjects.