Alpaslan Özgün

MicroRNA-21 as an Indicator of Aggressive Phenotype in Breast Cancer

Objective: The recently discovered microRNAs (miRNAs) are non-protein-coding, endogenous small RNAs. The aim of this study was to investigate the relationship between microRNA-21 (miR-21) and the clinicopathological features of breast cancer. Materials and Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from 15 patients who had undergone surgery for primary breast cancer. The miR-21 expression levels in normal and cancer tissues were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction (real-time qRT-PCR). The correlations between the miR-21 expression level and the stage of disease, the tumor size, lymph node involvement, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, and disease-free survival (DFS) were investigated. Results: The miR-21 expression levels were significantly higher in patients with stage III disease, patients with more than 3 axillary lymph node metastases and HER2-positive patients than in patients with stage I-II disease, patients with 1-3 axillary lymph node metastases and HER2-negative patients (p = 0.005, p = 0.037, and p = 0.014, respectively). Patients with high miR-21 expression level had a significantly shorter DFS than patients with low miR-21 expression level (median DFS: 18 and 56 months, respectively; p = 0.004). Conclusion: These results show that miR-21 is an indicator of an aggressive breast cancer phenotype and that it may be a new therapeutic target in the treatment of breast cancer in the future.

Mean platelet volume as a prognostic marker in metastatic colorectal cancer patients treated with bevacizumab-combined chemotherapy.

BACKGROUND Recent studies have revealed a prognostic impact of the MPV (mean platelet volume)/platelet count ratio in terms of survival in advanced non-small cell lung cancer. However, there has been no direct analysis of the survival impact of MPV in patients with mCRC. The aim of the study is to evaluate the pretreatment MPV of patients with metastatic and non-metastatic colorectal cancer (non-mCRC) and also the prognostic significance of pretreatment MPV to progression in mCRC patients treated with bevacizumab-combined chemotherapy. MATERIALS AND METHODS Fifty-three metastatic and ninety-five non-metastatic colorectal cancer patients were included into the study. Data on sex, age, lymph node status, MPV, platelet and platecrit (PCT) levels were obtained retrospectively from the patient medical records. RESULTS The MPV was significantly higher in the patients with mCRC compared to those with non-mCRC (7.895±1.060 versus 7.322±1.136, p=0.013). The benefit of bevacizumab on PFS was significantly greater among the patients with low MPV than those with high MPV. The hazard ratio (HR) of disease progression was 0.41 (95%CI, 0.174-0.986; p=0.04). In conclusion, despite the retrospective design and small sample size, MPV can be considered a prognostic factor for mCRC patients treated with bevacizumab-combined chemotherapy.

Immunoregulatory Function of HLA-G in Gastric Cancer

BACKGROUND Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. MATERIALS AND METHODS We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. RESULTS There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival. CONCLUSIONS We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.

Nesfatin-1 in advanced lung cancer patients with weight loss.

The cachexia occurs frequently in lung cancer patients. Among appetite regulatory peptides, alteration of expressions of leptin and ghrelin is demonstrated in cachectic cancer patients, but nesfatin-1 has not been yet studied in cancer. We investigated serum nesfatin-1 level in advanced lung cancer patients. Forty-one lung cancer patients and 24 healthy subjects were included to the study. Nesfatin-1 serum levels were analyzed by ELISA kit. Serum nesfatin-1 levels were lower in lung cancer patients than in healthy subjects (0.52±0.19ng/ml vs 0.75±0.23ng/ml; p<0.001). In lung cancer patients with weight loss, nesfatin-1 levels were decreased compared to the patients without weight loss (0.44±0.16ng/ml vs 0.63±0.18ng/ml; p<0.001). Whereas, there were no any difference between patients without weight loss and control subjects (0.63±0.18ng/ml vs 0.75±0.23ng/ml; p:0.129) or between SCLC and NSCLC patients (0.53±0.18ng/ml vs 0.52±0.20ng/ml; p:0.458). No significant correlation was found between serum nesfatin-1 values and BMI. In conclusion, loss of fat mass may decrease serum nesfatin-1 level in lung cancer patients with weight loss. The future studies which explore biological significance of low serum nesfatin-1 level in cancer are needed.

Hemicentral Retinal Artery Occlusion in a Breast Cancer Patient Using Anastrozole

Background: Anastrozole, an aromatase inhibitor, is commonly used in the adjuvant treatment of breast cancer. Anastrozole treatment is associated with a risk of thromboembolic events and retinal vascular side effects. Herein, we present a case of hemicentral retinal artery occlusion diagnosed in a breast cancer patient using anastrozole. Case Report: A 53-year-old woman with a hypertensive and diabetic background was admitted to our hospital with breast cancer. Anastrozole treatment was started after surgery, adjuvant chemotherapy, and radiotherapy. Sudden painless loss of vision in the patient’s right eye occurred within 13 months of Anastrozole treatment. A fluorescein angiogram revealed hemicentral retinal artery occlusion. Conclusion: To the best knowledge of the authors, this is the first report of hemicentral retinal artery occlusion in an anastrozole user.

Hyperammonemic encephalopathy in a patient with primary hepatic neuroendocrine carcinoma

A 53-year-old male patient was admitted to our hospital with abdominal pain in the right upper quadrant. There was no change in laboratory investigations other than a slight increase in serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT). Computed tomography (CT) of the abdomen showed multiple hepatic nodular lesions in the liver. Tru-cut biopsy of the lesions was reported as well-differentiated neuroendocrine carcinoma. The patient received sandostatin treatment. After a few days, the patient was hospitalized in the intensive care unit with disturbance of consciousness and clinical features suggestive of encephalopathy. Serum ammonia level was found highly elevated. After the treatment with l-ornithine-l-aspartate, a remarkable improvement in the level of patient’s sensorium occurred as well as a reduction in serum ammonia level within a few days. Transarterial chemoembolization (TACE) was performed one week later. The patient’s condition began to worsen along with increase in serum ammonia level and he died because of hyperammonemic encephalopathy. There are case reports of hyperammonemia with some malignancies such as multiple myeloma, plasma cell leukemia, and leiomyosarcoma, or in some patients who have received chemotherapy. This case may suggest an association between hyperammonemia and neuroendocrine tumors.

HLA-G in Testicular Germ Cell Tumors

Background: HLA-G is a non-classical major histocompatibility complex class I molecule. HLA-G expression has been found in various types of solid and hematological malignancies. It is also expressed in normal testicular and epididymal tissue. However, expression of HLA-G in testicular germ cell tumors has not been extensively studied. The aim of this study was to investigate whether HLA-G protein is present in different components of testicular germ cell tumors. Patients and Methods: 34 testicular cancer patients, for whom tumor tissue was available, were included in the study. Immunohistochemical staining was performed on tissue sections from formalin-fixed, paraffin-embedded tissue samples. Results: 7 (20.6%) patients had positive HLA-G staining in at least 1 component of the tumor sample. In 3 of 7 patients with intratubular germ cell neoplasia, staining with HLA-G was seen in this component. All of the choriocarcinoma components were strongly positive, and about 40% of teratoma components had immunopositivity. The components of seminoma and embryonal carcinoma, and most yolk sac tumors were negative. HLA-G immuno-positivity was not associated with tumor size, retroperitoneal lymph node involvement, distant metastasis, or relapse/refractory status. Conclusion: This study demonstrated that testicular choriocarcinoma and some teratomas express HLA-G, but not seminoma, embryonal carcinoma, and yolk sac tumors.

Clinicopathological Features and Survival of Young Turkish Patients with Testicular Germ Cell Tumors

BACKGROUND Testicular germ cell tumors (TGCTs) are a relatively common malignancy in young men. The aim of this study was to investigate the clinicopathological features and survival of young Turkish patients with TGCT. MATERIALS AND METHODS In this retrospective study, the clinical and pathological characteristics of young Turkish patients with TGCT who were monitored by the Department of Medical Oncology of a military hospital between 2008 and 2013 were investigated. Overall survival data were analyzed. RESULTS Ninety-six patients were included in the study. The mean age was 26.4 years. Among the patients, 17.7% had seminoma and 43.8% had mixed non-seminomatous germ cell tumors. Some 46.9% were Stage I, 30.2% were Stage II, and 22.9 were Stage III. Of the patients, 83.3% received chemotherapy, 25% underwent retroperitoneal lymph node dissection (RPLND), 3.1% received radiotherapy, and 12.5% were followed-up without treatment. In addition, 18.8% of the patients were administered salvage chemotherapy due to relapse or progression. The 5-year overall survival rate was 90.2% for all patients. The 2-year overall survival rate was 100% for Stage I patients, 94% for Stage II patients, and 70.2% for Stage III patients. The difference between the survival curves of stages was statistically significant (p=0.029). CONCLUSIONS In young Turkish patients with TGCT, good results were obtained with appropriate treatment, most receiving chemotherapy. The prognosis of the disease was good even in the advanced stage.

Platelet indices in patients with colorectal cancer

The interaction between cancer cells and platelets has been known for a long time. Although platelet indices have been also investigated in several clinical settings, it has not been exactly demonstrated in cancer patients. We investigated platelet indices in colorectal cancer patients and compared with healthy subjects. Two hundred and twenty-one colorectal cancer patients and 110 healthy subjects were enrolled into the retrospective study. Data were obtained from computerized medical records of our hospital. Medical record review was performed for all patients regarding thrombocyte indices. Platelet count (325.000/mm3 ± 265.000/mm3 vs 267.000/mm3 ± 67.000/mm3; p=0.025; respectively) and plateletcrit (Pct) (0.25% ± 0.10 vs 0.21 ± 0.05; p<0.001; respectively) were increased in patients compared with healthy subjects while mean platelet volume (MPV) and platelet distribution width (PDW) were similar. The platelet indices were not related to existence of metastasis or acute abdomen. Platelet count and Pct, but not MPV and PDW, are elevated in colorectal cancer patients. Future studies that investigate platelet morphology, function, and putative role of platelets in tumorigenesis and metatasis should be established.

Malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously: A case report

Malignant melanoma can be successfully treated when it is identified in its early stages, but the disease is associated with a poor prognosis when it is detected in an advanced stage. Papillary thyroid carcinoma is a thyroid cancer that has a good prognosis. The present study reports a rare case of malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously. The present patient was a 37-year-old male, in whom examination of a skin biopsy that was obtained from a lesion in the right retroauricular region revealed the lesion to be consistent with malignant melanoma. The patient underwent radical neck dissection upon the detection of malignant melanoma metastasis to the sentinel lymph node. Metastases of papillary thyroid carcinoma were detected in four out of 38 lymph nodes. The patient was then diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. The patient was administered with high-dose followed by moderate-dose interferon-α therapy for the treatment of malignant melanoma. The patient also received concurrent radioactive iodine therapy for the treatment of papillary thyroid carcinoma, at the same time as the interferon therapy. The two primary tumors of the patient were treated successfully. During therapy, no serious side-effects were observed, with the exception of fever caused by high-dose interferon therapy. Malignant melanoma and papillary thyroid carcinoma may occur concurrently, although this is rarely observed. The present study reports a rare case that demonstrates that the two tumors can be successfully treated simultaneously.