Clinical and prognostic significance of BRAF V600E mutation in non-metastatic cutaneous melanoma patients.

Because of the conflicting conclusions on BRAF mutations in the natural course of non-metastatic melanoma their prognostic significance is still controversial. The present study aims to assess the prevalence and prognostic significance of BRAF V600E mutation and apprehend its association with clinicopathologic features in stage I to III Turkish melanoma patients. A total of 93 adult stages I to III cutaneous primary melanoma patients were included in the study. BRAF V600E mutation was detected using the Real Time PCR. Median age was 52 years (range, 18 to 84) and 68.8% of the patients were men. Overall, BRAF V600E mutation was detected in 46.2% (43/93) of the patients. In stages I and II, trunk was the most frequently affected localization (47.1%) (p=0.05) and regression was found more prevalent in BRAF-mutant patients (38.5%) (p=0.05). Furthermore, males were predominant among stage III BRAF-mutant patients (80.8%) (p=0.05), and both superficially spreading histology subtype (45.0%) (p=0.05) and lower mitotic rate (36.4%) (p=0.02) also were more commonly associated with stage III BRAF-mutant patients. A significantly favorable relapse free survival was found in stage III node-positive BRAF-mutant patients (p=0.02), on the other hand BRAF status was not found to be associated with relapse free survival in stage I and stage II patients (p=0.3). Moreover, there was no overall survival association between stages and BRAF status (p=0.1 and p=0.2). In conclusion, there is no prognostic value of BRAF V600E mutation on overall survival in stage I-III melanoma patients, yet its presence might indicate a decreased risk for development of relapse and/or metastasis in stage III melanoma patients.

Relapse patterns in patients with local and regional cutaneous melanoma.

BACKGROUND: The differences in features and risk factors for recurrence after definitive surgical excision are yet to be determined. The aim of this study was to understand these factors influencing recurrence patterns with local and regional disease in these patients. METHODS: A total of 365 relapsed patients, of whom 196 presented with local disease (stage I-II) and 169 with regional disease (stage III), were investigated in this retrospective study. RESULTS: The median time to initial recurrence for stage I-II and stage III patients was 22.3 and 13.4 months, respectively. Stage III patients were found to have higher Clark levels (p = 0.0001) and thicker lesions (p = 0.0001), and they were more significantly associated with the absence of tumor-infiltrating lymphocytes (p = 0.02) than stage I-II patients. Stage III patients were more significantly associated with recurrences compared to the stage I-II patients (p = 0.0001). Locoregional relapses were significantly associated with stage I-II melanomas, whereas majority of the distant metastases occurred in stage III patients (p = 0.01). Pulmonary metastasis was most frequently observed and the distribution of the sites for distant metastases was similar in both groups of the patients. On univariate analysis, male sex, increased tumor depth, presence of ulceration, nodular histopathology, higher Clark level, higher mitotic rate, and presence of lymphovascular invasions were found to predict shorter time to relapse for stage I-II patients; whereas only nodular pathology, presence of ulceration, and high mitotic rate were found to be associated with poor relapse-free survival in stage III patients. However, on multivariate analysis, only mitotic rate maintained its significance for both clinical staging groups. CONCLUSION: Potential differences among early-stage melanoma patients, who developed recurrence, were noted and mitotic rate was found as the single significant prognostic factor for recurrence in both stage I-II and III patients.

Clinical significance of serum caveolin-1 levels in gastric cancer patients.

Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. MATERIAL AND METHODS: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. RESULTS: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). CONCLUSION: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer.

Neurotropism as a prognostic factor in cutaneous melanoma patients.

Neurotropism is a feature that is encountered rarely in melanoma and is considered to be associated with increased risk of local recurrence. However, its prognostic significance still remains controversial. The objective of this study was to deter- mine the clinical significance of neurotropism in cutaneous melanoma patients. A total of 519 cutaneous melanoma patients were enrolled into this study and their data were analyzed in a retrospective fashion. The melanomas without neurotro- pism (n=496; 95.6%) were larger in number than those with neurotropism (n=23; 4.4%). Compared to non-neurotropic melanomas, neurotropic melanomas were more likely localized in the extremities (p=0.007) and they were more frequently associated with non-superficial spreading histologic subtype (p=0.029), advanced Clark invasion level (IV-V) (p=0.007), thick Breslow depth (p=0.001), high mitotic rate (p=0.041), ulcerated lesions (p<0.001), lymphovascular invasion (p<0.001), and lymph node metastasis (p=0.013). The neurotropic melanomas were significantly associated with both unfavorable relapse-free survival (RFS) (p=0.045) and overall survival (OS) (p<0.001). However, neurotropism lost its prognostic signifi- cance in both RFS (p=0.767) and OS (p=0.644) in multivariable analyses. In conclusion, the presence of neurotropism predicts a greater risk for nodal involvement and is associated with worse survival in patients with cutaneous malignant melanoma, on the other hand it is not an independent risk factor when other powerful prognostic variables are considered.

Plantar melanoma is associated with certain poor prognostic histopathological factors, but not correlated with nodal involvement, recurrence, and worse survival.

BACKGROUND: Plantar surface melanoma affects the Caucasian race less likely than it does other races, e.g., the Asians and the Blacks. So far, small numbers of researches on plantar melanoma have yielded controversial results. The aim of this study was to define the histopathological and clinical characteristics pertinent to plantar melanoma and to compare them with melanomas that emerged in other sites by using a large group of patients from a single institution. PATIENTS AND METHODS: A total of 104 Turkish Caucasian plantar melanoma patients and 1065 patients with non-plantar melanomas were analyzed retrospectively. RESULTS: The plantar melanomas were found more frequently in females (p = 0.006) and in older patients (≥ 50 years old) (p = 0.002). Compared to melanomas in other sites, the plantar melanomas tended to have more acral lentiginous histopathology (p = 0.0001), deeper Clark invasion level (IV-V) (p = 0.01), and thicker Breslow depth (≥ 2 mm) (p = 0.05); and the plantar melanoma lesions were more likely ulcerated (p = 0.0001) and were correlated with more lymphovascular invasion (p = 0.001), fewer tumor infiltrating lymphocyte (p = 0.03), and less frequently associated with a preexisting melanocytic nevus (p = 0.01). However, no correlation was found between plantar localization and either nodal involvement or metastasis (p > 0.05). The recurrence free and overall survival times for plantar melanomas were similar to other sites (p > 0.05). 5-year overall survival rate in plantar melanoma patients were 59%. CONCLUSION: Even though plantar melanoma is associated with certain poor histopathological factors, it is not correlated with nodal involvement, recurrence, and poor survival.

Ultrasonic Spray Pyrolysis Deposited Copper Sulphide Thin Films for Solar Cell Applications.

Polycrystalline copper sulphide (Cu x S) thin films were grown by ultrasonic spray pyrolysis method using aqueous solutions of copper chloride and thiourea without any complexing agent at various substrate temperatures of 240, 280, and 320°C. The films were characterized for their structural, optical, and electrical properties by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive analysis of X-rays (EDAX), atomic force microscopy (AFM), contact angle (CA), optical absorption, and current-voltage (I-V) measurements. The XRD analysis showed that the films had single or mixed phase polycrystalline nature with a hexagonal covellite and cubic digenite structure. The crystalline phase of the films changed depending on the substrate temperature. The optical band gaps (Eg ) of thin films were 2.07 eV (CuS), 2.50 eV (Cu1.765S), and 2.28 eV (Cu1.765S-Cu2S). AFM results indicated that the films had spherical nanosized particles well adhered to the substrate. Contact angle measurements showed that the thin films had hydrophobic nature. Hall effect measurements of all the deposited Cu x S thin films demonstrated them to be of p-type conductivity, and the current-voltage (I-V) dark curves exhibited linear variation.

Clinical significance of serum protease activated receptor1 levels in patients with lung cancer.

OBJECTIVE: Protease-activated receptors (PAR) are G protein coupled receptors and they regulate many biological processes, including coagulation and cell survival and they might be good markers in some types of malignant tumors, providing useful information in diagnosis and prognosis. The objective of this study was to determine the clinical significance of the serum levels of PAR1 in lung cancer patients. PATIENTS AND METHODS: Eighty patients with lung cancer were enrolled into this study. Serum PAR1 levels were determined by the solid-phase sandwich ELISA method. Median age was 58.5-years old, range 36 to 80 years. RESULTS: The majority of the patients had NSCLC (85%) and stage IV disease (56%). The baseline serum PAR1 concentrations of the lung cancer patients were significantly higher than control group (median values 26.45 ng/mL v 0.07 ng/mL, p < 0.001). However, clinical variables including age, gender, histology, stage of disease, and response to chemotherapy were not found to be correlated with serum PAR1 levels (p > 0.05). Moreover, it failed to show any prognostic value on the survival of the lung cancer patients. CONCLUSIONS: The serum levels of PAR1 might have a diagnostic value in lung cancer patients. However, its predictive and prognostic values were not determined.

Plasma homocysteine, folate and vitamin B12 levels in patients with lung cancer.

AIM: Disorders in the metabolism of homocysteine and B vitamins, which are involved in a one-carbon transfer reaction and important for DNA synthesis and methylation, have been hypothesized to be associated with carcinogenesis. The purpose of this study is to evalu-ate the levels of homocysteine, vitamin B12 and folic acid in patients with newly diagnosed lung cancer and determines whether they might be used as an accurate tumor marker for monitoring the patients if they are found to be elevated in lung cancer. MATERIALS AND METHODS: Forty male patients with lung cancer were included in this study. Age-matched forty healthy males who had not malignant disease or had not received any drug affecting plasma homocysteine levels were selected as control group. Homocysteine, vitamin B12 and folate levels were measured in the samples obtained from the patients and controls. RESULTS: Mean age of the patients with lung cancer was 58.7 ± 9.9 years. All the patients were cigarettes smokers. Mean daily consumption of cigarettes was 2.0±0.7 packs and mean duration of smoking was 30 ± 11 years. Histologic type of carcinoma was found to be squamous cell carcinoma in 55%, adenocarcinoma - in 35%, and small cell carcinoma - in 10% of the cases. Clinical stage was stage IA in 20%, stage IB - in 20%, stage IIA - in 2.5%, stage IIB - in 10%, stage IIIA - in 12.5%, stage IIIB - in 20%, and stage IV - in 15% of the cases. Mean homocysteine level was 15.3 ± 7.3 µmol/l in the patients with lung cancer while 9.8 ± 2.6 µmol/l in controls. Homocysteine level was significantly higher in the patients with lung cancer compared to control group (p < 0.001). Mean folate level was 4.3 ± 1.8 pg/ml in cancer cases while 6.1 ± 2.3 pg/ml in controls. That is to say, plasma folate levels were significantly lower in cases of lung cancer compared to controls (p < 0.001). There was no significantly difference between groups with regard to B12 levels (mean B12 level was 234 ± 99 and 240 ± 104 ng/ml in the patients with lung cancer and controls, respectively, p = 0.78). Plasma homocysteine, vitamin B12 and folate levels did not show significant difference with respect to histologic type of carcinoma. No significant correlation was found between plasma homocysteine, vitamin B12, folate levels and number of cigarettes smoked per day, duration of smoking, age of the patient, and clinical stage of carcinoma. There was also no correlation between number of cigarettes smoked per day, duration of smoking, age of the patient and clinical stage of carcinoma. A possible inverse correlation between plasma homocysteine, vitamin B12 and folate levels was not observed. CONCLUSION: In conclusion, high plasma homocysteine and low folate levels could be associated with lung cancer. However, further studies performed on large patient population are needed.

Preoperative chemotherapy for T2 breast cancer is associated with improved surgical outcome.

BACKGROUND: The aim of this study is to compare the clinical outcome in T2 breast cancer patients who underwent preoperative chemotherapy (PC) and who did not. The study also tried to define a subgroup of patients, who are more beneficial after PC in terms of lower re-excision rates, better cosmetic results and local recurrence free survival. MATERIALS AND METHODS: 251 consecutive patients treated for nonmetastatic T2 invasive breast cancer were analyzed retrospectively. Of those; 141 underwent primary surgery (PS) followed by chemotherapy, whereas 110 were treated with combination of PC and surgery. RESULTS: The patients who were treated with PC had a significantly higher incidence of negative margins and lower rate of re-excision (5% vs. 16%, p = 0.02). Of all patients attempted breast conserving surgery (BCS), patients in the PC group were more likely to undergo BCS as their definitive operation compared to patients with PS group (BCS rates; PC group: 99% vs. PS group: 92%, p = 0.05). Multifocal disease (OR: 7, 95% Cl, 2.7-18.4, p = 0.0001) and PC (OR = 0.2; 95% CI, 0.06-0.72, p = 0.01) were factors associated with margin positivity in patients treated with BCS. There was no statistically significant difference in 5 year local-recurrence free survival rates between 2 groups. CONCLUSIONS: Our study shows that PC significantly decreases the re-excision in patients undergoing BCS with primary T2 breast tumors. This data suggests that any patient with a tumor greater than 2 cm might be considered for PC to increase BCS success with final negative margins.

Restoration of euthyroidism does not improve cardiovascular risk factors in patients with subclinical hypothyroidism in the short term.

Subclinical hypothyroidism (SH) is being accepted as a condition that is associated with increased risk of cardiovascular disease. Restoration of euthyroidism might be involved in prevention of cardiovascular disease. Thus, we evaluated biochemical risk factors of 75 patients with SH without evidence of any other diseases before and after restoration of euthyroidism and compared to 27 healthy controls. Before and a mean of 18.2+/-4.4 weeks after restoration of euthyroidism, serum total and LDL cholesterol, lipoprotein (Lp) (a), total homocysteine (t-Hyc) and highly sensitive C-reactive protein (hsCRP) levels were analyzed. Pre-treatment levels of TSH (10.04+/-5.36 vs 1.74+/-1.1 mIU/l, p<0.05), total cholesterol (204+/-68 vs 179+/-26 mg/dl, p<0.05) and LDL cholesterol (129+/-50 vs 106+/-16 mg/dl, p<0.05) were significantly higher than controls while Lp (a), t-Hyc, and hsCRP levels were not different. None of these biochemical risk factors have improved after euthyroidism in patients with SH with average dose of 85+/-30 microg/day, when compared to pre-treatment levels. Only in a subgroup of patients (no. 30) with higher TSH levels (>10 mIU/l), did serum LDL cholesterol levels decrease significantly (139+/-38 vs 112+/-35 mg/dl, p<0.05). Lp (a), t-Hyc and hsCRP levels were not significantly different after treatment with levothyroxine therapy even in this subgroup of patients. We conclude that clinical management of SH does not contribute to prevention of cardiovascular disease in the short term, and monitoring risk factors of cardiovascular disease does not offer additional benefits for treating patients with SH.