Kayhan Erturk

Presence of histological regression as a prognostic factor in cutaneous melanoma patients.

Regression is caused by a host immunological response primarily characterized by lymphocytic infiltration directed against melanoma cells. The prognostic significance of regression remains controversial in cutaneous melanoma patients. The aim of this study was to determine the clinical significance of the histological regression status in patients with cutaneous melanoma. A total of 664 patients with a pathologically confirmed cutaneous melanoma were enrolled into this study and were investigated retrospectively. The median age of the patients was 51 years, ranging in age from 16 to 104 years. The majority of them had lesions without regression (n=495; 74.5%) and others had lesions with regression (n=169; 25.5%). Melanoma patients with regression were more frequently males (60.1 vs 51.7%; P=0.038) and had axial localized lesions (67.5 vs 53.7%; P=0.002), superficial spreading histologic subtype (73.2 vs 49.1%; P=0.000), thin Breslow depth (<2 mm) (44.6 vs 33.5%; P=0.01), and the presence of tumor-infiltrating lymphocytes (74.4 vs 60.0%; P=0.001) than those without regression. However, regression was not significantly associated with age, Clark level, mitotic rate, ulceration, vertical growth phase, neurotropism, lymphovascular invasion, nor association with a pre-existing melanocytic nevus. Similarly, no significant correlations were found between regression and lymph node involvement, recurrence, nor metastasis of disease. Patients with, nodular pathology, advanced Clark invasion level (IV–V), thick Breslow depth (≥2 mm), high mitotic rate (>3/mm2), ulceration, vertical growth phase, neurotropism, lymphovascular invasion, lymph node involvement, metastasis, and recurrence of disease, and male patients had poor prognostic variables for both relapse-free survival and overall survival. However, the presence of regression was not associated with relapse-free survival (P=0.093) nor overall survival (P=0.113) similar to other factors such as age, tumor localization, tumor-infiltrating lymphocytes, and association with a pre-existing melanocytic nevus. Similar insignificant P values were also observed in multivariate analyses (P=0.115 and 0.816, respectively). In conclusion, the presence of histological regression plays no prognostic role in nodal involvement nor survival in patients with cutaneous melanoma.

Recurrence behavior in early-stage cutaneous melanoma: pattern, timing, survival, and influencing factors.

Nearly one-third of all melanoma patients will experience disease recurrence and the majority of the relapses eventually develop metastatic disease as a consequence of disease progression in the early-stage melanoma patients. As very few number of studies have investigated the natural recurrence history of early-stage cutaneous melanoma at the first relapse, we analyzed the time until recurrence along with the patterns and outcomes of the relapses in this retrospective study. A total of 332 patients who were initially diagnosed with nonmetastatic melanoma and developed recurrence during the disease course and/or follow-up were included in the analysis. Locoregional relapse alone defined regional lymph node metastases, distant skin, subcutaneous, and satellite/in-transit metastases. Nearly half of the primary recurrences were locoregional metastasis alone (50.6%), followed by mixed locoregional and distant metastases (25.9%), and distant metastases alone (23.5%). In terms of distant metastasis, the lung was the most frequently affected site (30.7%), followed by bone (15.7%), liver (13.9%), and brain (10.8%). The time intervals for each of the recurrence patterns and distant metastasis sites were identical and nearly 16 months. Nearly two-thirds of the relapses occurred within the first 2 years of diagnosis. A significant survival advantage was observed in locoregional relapse alone compared with other relapse patterns (P<0.0001). In conclusion, about half of the melanoma patients developed locoregional relapse alone and it was found to be associated with a favorable prognosis for outcome. Because nearly two-thirds of the relapses occurred within the first 2 years of diagnosis, we suggest that all early-stage melanoma patients should be kept under a strict, thorough, and close follow-up program for at least 2 years following the diagnosis.

Tumor Infiltrating Lymphocytes (TILs) May be Only an Independent Predictor of Nodal Involvement but not for Recurrence and Survival in Cutaneous Melanoma Patients

ABSTRACT Tumor infiltrating lymphocytes (TILs) invade and disrupt melanoma cells and their clinical roles remain controversial. In this study, we aimed to determine the clinical significance of the TILs status in cutaneous melanoma patients (CMPs). Of 750 CMPs enrolled into this study 486 (64.8%) had lesions with TILs. The patients with TILs more likely had nodular histology, presence of histological regression, and absence of regional lymph node involvement. However, its presence was not associated with outcome. In conclusion, presence of TILs may be only an independent predictor for absence of nodal involvement but it is not associated with recurrence and survival in CMPs.

Scalp melanoma is associated with high mitotic rate and is a poor prognostic factor for recurrence and outcome

A small subset of head and neck melanoma, scalp melanoma comprises 3–5% of all cutaneous melanomas. So far, small numbers of researches on scalp melanoma have yielded controversial results. In this trial, we aimed to define the histopathological and clinical features specific to scalp melanoma and to compare them with melanomas that occurred on other sites by using a large group of patients from a single institution. The data of 93 patients with scalp melanoma and 1076 patients with melanomas on other sites were analyzed retrospectively. The median age of the patients was 53 (range 18–83) years. The scalp melanomas were found more frequently in male patients (79.6 vs. 52.0%, P=0.001) and they tended to have nodular histology (41.1 vs. 29.2%, P=0.01), with a higher mitotic rate (>3/mm2) (56.9 vs. 40.9%, P=0.01). However, the scalp melanoma was not significantly associated with other histopathological parameters, for example, age, Clark invasion level, Breslow thickness, ulceration, regression, lymphovascular invasion, neurotropism, tumor-infiltrating lymphocyte, and BRAF mutation analysis. Besides, no correlation was found between scalp localization and either nodal involvement or metastasis (P>0.05). The scalp patients had poorer survivals compared with those with other sites. The median survival time and 5-year recurrence-free survival rates for scalp and other sites in patients were 15.6 months and 45.1% versus 23.5 months and 63.6%, respectively (P=0.001). Similarly, the median overall survival times and 5-year overall survival rates in scalp and other sites in patients were 25.6 months and 44.1% versus 28.7 months and 62.9%, respectively (P=0.0001). In conclusion, scalp melanoma patients correlate with a high mitotic rate and are associated with poorer survival than patients with melanomas on other sites.

Clinical Signifıcance of Serum Ykl-40 (Chitinase-3-Like-1Protein) as a Biomarker in Melanoma: an Analysis of 112 Turkish Patients

Background: Angiogenesis plays an essential role in tumor growth and serum levels of YKL-40, a strong angiogenic factor that promotes tumor vessel development, has been found to be elevated in various cancers. We here investigated correlation between melanoma parameters and serum YKL-40 levels, to assess potential diagnostic, prognostic and predictive values. Material and Methods: Data for 112 pathologically confirmed cutaneous melanomas of any stage were examined retrospectively. ELISA assays were used to measure serum YKL-40 in plasma samples. Results: The baseline serum YKL-40 levels were significantly higher in patients than healthy controls (174.88 vs 120.10 ng/mL, p<0.001). However, values did not correlate with clinicopathological parameters, (p>0.05), and furthermore there was no apparent prognostic influence on melanoma survival (HR: 1.568; 95% CI, 0.580-3.051; p=0.838). Conclusion: Serum YKL-40 can be useful for diagnosis of melanoma, but reliability in assessing prognosis is questionable. We believe that efforts should be made to understand the interaction between YKL-40 and the tumor environment, and establish whether it might be the target for treatment of malignancies.

Clinical significance of serum claudin-1 levels in melanoma patients.

Claudins are the most important structural and functional components of tight-junction integral membrane proteins. They play roles in major cellular functions including growth and adhesion and are responsible for regulating the paracellular transport of molecules. The objective of this study was to determine the clinical significance of the serum levels of claudin-1, an oldest and important member of the claudin family, in melanoma patients. A total of 98 patients with a pathologically confirmed melanoma were enrolled into this study. Serum claudin-1 concentrations were determined by the solid-phase sandwich enzyme-linked immunosorbent assay method. Age-matched and sex-matched 43 healthy controls were included in the analysis. The median age at diagnosis was 51 years, ranging from 16 to 85 years. The majority of the patients were male (61%) and had axial localized (54%) and metastatic disease (61%). Moreover, most of the patients with metastatic disease had M1c (73%). The baseline serum claudin-1 levels of the melanoma patients were significantly lower than those of control subjects (median values 9.17 vs. 13.82 ng/ml, respectively, P<0.001). However, known clinical variables including age of the patient, sex, site of lesion, histology, lymph node involvement, stage of disease, serum lactate dehydrogenase levels, and response to chemotherapy were not found to be correlated with serum claudin-1 concentrations (P>0.05). Similarly, serum claudin-1 concentration was found to have no prognostic role in survival (P=0.524). In conclusion, serum levels of claudin-1 may have a diagnostic value in melanoma patients. However, its predictive and prognostic value has not been determined.

Serum activated leukocyte cell adhesion molecule and intercellular adhesion molecule-1 in patients with gastric cancer: Can they be used as biomarkers?

Cellular adhesion molecules might be used as markers in diagnosis and prognosis in some types of malignant tumors. The purpose of this study was to determine the clinical significance of the serum levels of activated leukocyte cell adhesion molecule-1 (ALCAM) and intercellular adhesion molecule-1 (ICAM-1) in gastric cancer (GC) patients. Fifty-eight GC patients and 20 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 59.5 years (range 32-82 years). Tumor localizations of the majority of the patients were antrum (n=42, 72.4%) and tumor histopathologies of the majority of the patients were diffuse (n=43, 74.1%). The majority of the patients had stage IV disease (n=41, 70.7%). Thirty six (62.1%) patients had lymph node involvement. The median follow-up time was 66 months (range 1-97.2 months). At the end of the observation period, 26 patients (44.8%) were dead. The median survival for all patients was 21.4±5 months (%95 CI, 11.5-31.3). The 1-year survival rates were 66.2%. The baseline serum ALCAM 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 ICAM-1 between the patients and controls (p=0.232). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p>0.05). Tumor localization (p=0.03), histopathology (p=0.05), and response to chemotherapy (p=0.003) had prognostic factors on survival. Neither serum ALCAM levels nor serum ICAM-1 levels were identified to have a prognostic role on overall survival (ICAM-1 p=0.6, ALCAM p=0.25). In conclusion, serum levels of ALCAM were found to have diagnostic value in GC patients.

Clinical significance of serum Protease-Activated Receptor-1 (PAR-1) levels in patients with cutaneous melanoma

Background Protease-Activated Receptor-1 (PAR-1) plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of PAR-1in cutaneous melanoma patients. Methods A total of 60 patients with a pathologically confirmed diagnosis of cutaneous melanoma were enrolled into this study. Serum PAR-1concentrations were determined by the solid-phase sandwich ELISA method. Results No significant difference in serum PAR-1 levels between melanoma patients and healthy controls was found (p = 0.07). The known clinical variables including age of patient, gender, site of lesion, histology, stage of disease, serum LDH levels and chemotherapy responsiveness were not correlated with serum PAR-1 concentrations (p > 0.05). Likewise, serum PAR-1 concentration had also no prognostic role on survival (p = 0.41). Conclusion Serum levels of PAR-1 have no diagnostic, predictive and prognostic roles in cutaneous melanoma patients. General significance Measurement of PAR-1 in serum is not a clinical significance in cutaneous melanoma patients.

Digital clubbing as a first clinical presentation of pulmonary metastases in cutaneous melanoma

ABSTRACT Digital clubbing is a paraneoplastic phenomenon usually associated with non-small cell lung cancer. We report the development of clubbing in a 49-year old man diagnosed with cutaneous melanoma which had metastasized to the lungs. We also reviewed the literature to understand the association between metastatic melanoma and clubbing. Previous reports of melanoma associated with hypertrophic osteoarthropathy (HOA) are extremely rare; only 7 cases. In all these patients digital clubbing was the main component of the HOA. However, our patient developed digital clubbing in the absence of other features of HOA. Therefore, to our knowledge, our report is the first in the literature. In conclusion, it should be kept in mind that digital clubbing might be associated with metastatic melanoma to the lung, notwithstanding rarely, and successful treatment of the underlying disease is associated with rapid resolution of the clubbing, as occurs in most patients with paraneoplastic syndromes.

Acral Lentiginous Melanoma Is Associated with Certain Poor Prognostic Histopathological Factors but May Not be Correlated with Nodal Involvement, Recurrence, and a Worse Survival

Background/Aims: Acral lentiginous melanoma (ALM) is a small subtype of melanoma affecting Caucasians far more often than other ethnic groups, such as blacks, Hispanics, and Asians. Only a few studies have yielded controversial results on ALM so far. The aim of this study was to define the histopathological and clinical expressions of ALM and to compare them with those of non-ALM in a large group of Turkish patients from a single referral institution. Methods: One hundred two ALM patients were analyzed retrospectively. Results: The median age of the patients was 58 years. The lower limbs (the thigh and leg as well as the foot) were predominantly affected (78%) and cases were mostly nonungual (89%). ALM were found more frequently in females (p = 0.04). They were ulcerated (p = 0.0001), they were associated with neurotropism (p = 0.0001), they lacked the BRAF mutation (p = 0.03), and they less often coexisted with a preceding melanocytic nevus (p = 0.0001). No correlations were found between ALM and either nodal involvement or distant metastasis. The recurrence-free survival and overall survival rates for ALM patients were similar to those of patients with other histopathologies. The 5-year recurrence-free survival and 5-year overall survival rates for ALM patients were 58.7 and 59%, respectively. Conclusion: Although ALM is associated with some aggressive histopathological factors, it may not correlated with nodal involvement, recurrence, or poor survival.