Identification of four novel variant in the AMHR2 gene in six unrelated Turkish families.

PURPOSE: Persistent Müllerian duct syndrome (PMDS) is characterized by the persistence of Müllerian structures in male with normal phenotype. Most cases occur as a result of mutations in the anti-Müllerian hormone (AMH) or AMHR2 genes. In this study, we aim to discuss the results of clinical, laboratory, and molecular genetic analysis of cases detected to have AMHR2 gene mutation. METHODS: A total of 11 cases from 6 families were included in the study. AMHR2 gene mutation analyses were performed by sequencing of the coding exons and the exon-intron boundaries of the genes. The American College of Medical Genetics guidelines were used for the classification of the detected variants. RESULTS: Six of the 11 cases were admitted due to bilateral undescended testes and five cases due to inguinal hernia (three transverse testicular ectopia and two hernia uterus inguinalis). All cases had normal AMH levels. Seven different variants were identified in the six families. The variants detected in four cases were considered novel (c.78del, c.71G > A, c.1460dup, c.1319A > G). Two of the novel variants were missense (exon 2 and exon 10) mutations, one was deletion (exon 2), and one duplication (exon 11). CONCLUSION: We identified four novel mutations in the AMHR2 gene resulting in PMDS. Duplication mutation (c.1460dup) in the AMHR2 gene causing PMDS was demonstrated for the first time. The most important complications of PMDS are infertility and malignancy. Early diagnosis is vital to preventing malignancy. Vas deferens and vascular structures may be injured during orchiopexy. Therefore, patients should always be referred to experienced clinics.

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.

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.

Clinical significance of serum tenascin-C levels in breast cancer.

Tenascin-C (TNC) is a key molecule in tissue remodeling, and high levels are observed in many diseases, including heart failure, thrombosis, atherosclerosis, and cancer. High TNC expression by immunohistochemical analysis has been shown in invasive and metastasizing tissues from a variety of cancers, including colon, lung, brain, and breast. This study was conducted to investigate the serum level of TNC in breast cancer patients and its relationship with tumor progression and known prognostic parameters. Ninety-six breast cancer patients were enrolled into the study. Serum samples were obtained on first admission before adjuvant and metastatic treatments were given and at follow-up. Serum TNC levels were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) method. Median age of diagnosis was 48 years old (range, 29-80). Thirty-seven (39 %) patients had metastatic breast cancer. The mean TNC levels were found to be significantly higher in patients with breast cancer (344.1 ± 42.4 pg/mL) compared to those in healthy controls (137.2 ± 26.8 pg/mL) (p = 0.005). Serum TNC level in grade 3 tumors was found to be significantly higher than in grades 1-2 tumors (p = 0.04). No correlation was detected between serum TNC levels and other prognostic parameters analyzed, including presence of metastasis, lymph node involvement, and tumor size. Serum TNC level had no significantly adverse effect on survival in univariate and multivariate analyses (p = 0.65 and p = 0.85, respectively). In conclusion, although serum TNC levels are elevated, it has no predictive or prognostic roles on survival in breast cancer patients.

Is there any diagnostic value of serum protease-activated receptor-1 (PAR1) levels on determination of epithelial ovarian carcinoma?

The role of molecular markers in ovarian cancer is still a matter of debate. Protease-activated receptor-1 (PAR1) might be a good marker in some types of malignant tumors and might provide useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of PAR1 in regard to diagnostic, predictive, and prognostic value in epithelial ovarian cancer (EOC) patients. Forty-four EOC patients were enrolled in this study. Serum PAR1 levels were determined by enzyme-linked immunosorbent assay (ELISA) method. Twenty-five age- and sex-matched healthy controls were included in the analysis. The median age of patients was 58 years old, ranging from 22 to 83 years, where most of them had advanced disease (stage III-IV) (n = 40, 91%). The median serum PAR1 values were significantly elevated in patients compared to healthy controls (1.52 ng/ml vs. 1.13 ng/ml) (p = 0.03), whereas any clinical variables including response to chemotherapy did not associate with serum assay (p > 0.05). Progression-free survival (PFS) and overall survival (OS) of patients who did not respond to chemotherapy nor had platinum resistance in relapsed disease were poorer in the analyses. On the other hand, serum PAR1 levels showed no significant adverse effect on either PFS or OS (p = 0.43 and p = 0.49, respectively). These results proved that baseline serum PAR1 levels of patients with EOC were significantly higher than those of healthy people. However, these assays suggested no predictive or prognostic value in this group of patients.

Clinical significance of serum circulating insulin-like growth factor-1 (IGF-1) mRNA in hepatocellular carcinoma.

The principal aim of our study was to investigate the usefulness of serum protein and circulating mRNA of insulin-like growth factor-1 (IGF-1) as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). Fifty-four HCC patients and age- and sex-matched 20 healthy controls were enrolled into this study. Pretreatment serum IGF-1 and IGF-1 mRNA were determined by the solid-phase sandwich ELISA and quantitative RT-PCR method, respectively. The median age at diagnosis was 60 years, range 36-77 years; where majority of group were male (n = 48, 88.8%). All patients had cirrhotic history. Forty-six percent (n = 25) of patients had Child-Pugh score A, 30% (n = 16) had score B or C. All of the patients were treated with local therapies and none of them received sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p = 0.04), whereas no significant difference was observed for IGF-1 protein levels between the two group (p = 0.18). Patients with history of HBV infection, who were not treated, and who received multiple palliative treatment for HCC had higher serum IGF-1 mRNA levels (p = 0.03, 0.03, and 0.05, respectively). Poor performance status (p < 0.001), viral etiology of cirrhosis (p = 0.03), larger tumor size (p = 0.01), lower serum hemoglobin levels (p = 0.03), and not be treated for HCC (p = 0.001) related to worse survival. However, neither serum IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p = 0.53 and 0.42, respectively).

Clinical significance of serum hepatocyte growth factor (HGF) levels in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. This study was conducted to investigate the serum levels of hepatocyte growth factor (HGF)in HCC patients and the relationship with tumor progression and known prognostic parameters. Fifty-four patients with HCC were investigated. Pretreatment HGF levels were employed the quantitative sandwich enzyme immunoassay technique (ELISA). Age and sex matched 20 healthy controls were included in the analysis. The median age of the patients was 60 years (range 36-77 years); where males consistituted of majority of the group (88.8%). All of patients had cirrhotic history. Fourty-six percent (n = 25) of patients had Child-Pugh Score A, 30% (n = 16) had Score B or C. All of the patients were treated with local therapies but none of them received sorafenib. The baseline serum HGF levels were significantly higher in patients with HCC than in the control group (p < 0.001). Male patients had higher serum HGF levels compared with female patients (p = 0.01). Serum HGF levels were significantly higher in the patients with elevated serum ALT levels than others with normal serum ALT levels (p = 0.05). Poor performance status (p < 0.001), viral etiology of cirrhosis (p = 0.03), larger tumor size (p = 0.01), lower serum hemogloblin levels (p = 0.03), and not be treated for HCC (p = 0.001) related to worse survival. However, serum HGF did not have significantly adverse effect on survival (p = 0.58). Despite serum HGF levels were found diagnostic value, serum HGF levels had no prognostic value in patients with HCC.

The diagnostic, predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer.

The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48 years (range 29-80 years). Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6 ± 1.7 and 35.5 ± 1.5 months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (p < 0.001). There was no significant difference in the serum levels of VCAM-1 between the patients and controls (p = 0.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p > 0.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (p = 0.04 and p = 0.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (p < 0.001 and p < 0.001, respectively). Neither serum VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 p = 0.76 and p = 0.32; EpCAM p = 0.16 and p = 0.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients.

Oral etoposide as first-line therapy in the treatment of patients with advanced classic Kaposi's sarcoma (CKS): a single-arm trial (oral etoposide in CKS).

BACKGROUND: Classic Kaposi's sarcoma (CKS) affects an elderly population; it is important to have effective treatment options with high activity and relatively low toxicity, and availability to be used for long periods. OBJECTIVE: We investigated the activity and safety of single-agent etoposide with an oral administration schedule in patients with advanced CKS. METHODS: Histologically confirmed, CKS patients were eligible for study. All had a negative test for HIV and good performance status. All patients received oral etoposide 50 mg twice daily for 10 days every 3 weeks. RESULTS: Thirty patients (median age 66 and 22 males) were enrolled into the study. The majority of them had non-metastatic, local advanced disease and symptoms in nearly half of patients. Complete and partial responses were observed in 10% and 77% of patients, respectively, giving an overall response rate of 87%. Stable disease occurred in the other 13% of patients. Treatment was well tolerated. Grade IV toxicity was not observed. Haematological toxicity was the principal dose-limiting side effect. Severe leucopaenia and neutropaenia were observed in 7% and 10% of patients respectively. No patient was complicated by febrile neutropaenia. Mild-moderate anaemia observed frequently, but only 3% of patients had severe anaemia and severe thrombocytopaenia was not observed. The 5-year overall survival rate was 92%. CONCLUSIONS: Single-agent oral etoposide is an effective treatment option and is acceptably toxic and easily administered. Therefore, we recommend the single agent of oral etoposide as the first-line chemotherapy for advanced CKS.

The role of surgical methods in the treatment of anorectal malignant melanoma (AMM).

PURPOSE: Anorectal malignant melanoma (AMM) is a rare tumor with a poor prognosis. The aim of this study was to investigate the clinicopathological characteristics and treatment outcomes in patients with AMM. METHODS: The study included 21 patients diagnosed with AMM between 2000 and 2010 that were evaluated with regard to age, sex, disease stage, treatment modality, and survival. Stage I, II, and III were defined as localized primary malignant melanoma, regional lymph node metastasis, and distant metastasis, respectively. RESULTS: In all, 12 (57%) patients were female and 9 (43%) were male ; median age was 61 years (range : 30-84 years). Among the 21 patients, 7 (47%) underwent abdominoperineal resection and 8 (53%) were treated using wide local excision. Four (19%) patients were classified as stage I, 10 (48%) as stage II, and 7 (33%) patients as stage III. In total, 10 patients received adjuvant therapy. Median overall and progression-free survival was 12 and 9 months, respectively. The 1-year and 5-year overall survival estimates were 59% and 42%, and progression free survival were 49% and 7%, respectively. Patients aged > 60 years (P = 0.145), female patients (P = 0.076), patients with localized disease (P = 0.045), patients that underwent wide local excision (P = 0.619), and patients that received adjuvant therapy (P = 0.962) had longer survival. CONCLUSIONS: The prognosis of AMM remains very poor and disease stage is the only predictor of survival. Abdominoperineal resection does not confer an advantage, in terms of survival, in patients with AMM.

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.

The contribution of countries and world regions in productivity of oncological publication.

BACKGROUND: To evaluate the contribution of different countries and world regions in scientific research in the field of oncological diseases. PATIENTS AND METHODS: We carried out an analysis of papers published in the meeting abstracts of ASCO and ESMO and their official journals, JCO and Annals of Oncology (Ann Oncol) during the time period 2000-2006 biennially, years 2000, 2002, 2004, and 2006. All meeting abstracts published in meeting abstract books and journal articles were included. RESULTS: North America and Europe with equal ratios were responsible for 95% and 80% of published oncological articles and meeting abstracts, respectively. These ratios showed a great difference on the basis of the journal and place of the meeting: American prefers JCO and ASCO and European favors Ann Oncol and ESMO. The number of countries contributed to the production of abstracts was two times more than that of the article production. Generally, there were relationship between the ratios of the majority of the countries in the production of articles and abstracts. However, several countries including Turkey, Korea, Spain, and Brazil have produced more abstracts; others (United States, The Netherlands, France, UK, and Switzerland) had more article production. CONCLUSION: Our study shows that developed world regions achieved a higher rate of research productivity than the other world regions.

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.

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.

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.

Prognostic significance of melanoma inhibiting activity levels in malignant melanoma.

This analytic (phase II) study aimed to investigate the hypothesis that the decline in serum melanoma-inhibiting activity (MIA) levels following initiation of treatment might have prognostic value. The mean serum lactate dehydrogenase (LDH), MIA and S100 levels in patients with malignant melanoma before treatment were higher than in the control group. Patients with visceral dissemination had much higher mean serum MIA levels than patients with nodal spread only. A regression model was constructed to analyse the prognostic factors in patients with advanced stage malignant melanoma. Therapy included surgical excision or lymph node dissection, hypofractionated radiotherapy, and immunotherapy or chemotherapy. Blood samples were collected within 24 h before the initiation of systemic treatment and two or three times more at 20-28 day intervals. Overall survival was investigated by univariate analysis, and correlation with clinical factors was compared using the log-rank test. Gender, primary tumour site, surgery, radiation therapy, serum S100 levels before systemic treatment and choice of chemotherapy were not correlated with the outcome. In addition to the stage of disease, low serum LDH levels before systemic treatment and a decline in serum MIA levels following initiation of systemic treatment predicted a favourable outcome. Metastasis to visceral organs was associated with higher serum MIA levels. Persistence of high serum MIA levels despite systemic treatment predicts an unfavourable prognosis.

Serum levels of the soluble adhesion molecules in patients with malignant melanoma.

The incidence of malignant melanoma has been steadily increasing over the past decades. CD 44 is a transmembrane glycoprotein which is implicated in a number of adhesive and migratory events. Downregulation of CD 44 is implicated in the metastatic process. P-Selectin is a member of the selectin family of cell surface molecules. The levels of P-Selectin in biological fluids may be elevated in subjects with a variety of pathological conditions. In malignant melanoma, elevation of the plasma level of soluble intercellular adhesion molecule-1 (sICAM-1) has been associated with a reduction in disease-free survival. This study was performed to investigate the differences in the serum concentrations of the adhesion molecules in patients with malignant melanoma. The study group consisted of 52 patients with malignant melanoma and 20 healthy subjects. No meaningful difference was observed for P-selectin and sICAM 1 levels. A statistically significant decrease was observed in the cancer patients for serum CD 44 levels.

Serum lactate dehydrogenase levels at presentation predict outcome of patients with limited-stage small-cell lung cancer.

Serum lactate dehydrogenase (LDH) is a biochemical parameter that is elevated in the majority of extensive-stage small-cell lung cancer (SCLC). In this study, distribution and prognostic importance of serum LDH in limited-disease SCLC were investigated. Serum concentrations of LDH were measured in 184 patients at initial examination. These results were compared with prospectively recorded clinicopathologic characteristics and patient outcome data. Significant positive association was found between LDH levels and weight loss, performance status, response to chemotherapy, and albumin but not between age, gender, and hemoglobin values. Patients with high concentrations of LDH had a significantly worse prognosis than did patients with normal levels. The probability of overall survival at 1 year was 60.2% in patients with normal serum LDH levels and 33.1% in patients with higher values (p = 0.0017). Also, the prognostic value of LDH on overall survival was shown in multivariate analysis (p = 0.05). At the time of diagnosis, serum levels of LDH appear to have a significant relation to outcome in patients with limited-stage SCLC.

Measurement of serum CA 19-9 may be more valuable than CEA in prediction of recurrence in patients with gastric cancer.

In 35 patients with recurrent gastric cancer who had undergone curative gastrectomy, serum carcinoembryonic antigen (CEA) and CA 19-9 (carbohydrate antigen) tumor marker levels were investigated. At least one tumor marker was elevated in 24 (68.6%) patients. The levels of serum CA 19-9 and CEA markers were increased in 20 (57.1%) and 12 (34.3%) patients, respectively. This difference was not statistically significant. However, it may be important in terms of clinical practice.