Clinicopathological Characteristics and Mutation Profiling in Primary Cutaneous Melanoma

WOS: 000353346500009PubMed ID: 25357015Background: The incidence of mutations in malignant melanoma varies remarkably according to the subtype of melanoma, and this in itself is affected by racial and geographical factors. Studies screening melanoma case series for different types of mutations are relatively rare. Method: The authors analyzed the frequency of various somatic point mutations of 10 genes in 106 primary cutaneous melanoma cases. The mutations (BRAF, NRAS, KIT, CDKN2A, KRAS, HRAS, PIK3CA, STK11, GNAQ, CTNNB1) were evaluated with real-time PCR-based PCR-Array through allele-specific amplification, and the results were correlated with various clinicopathological characteristics. Results: Mutations were found in 64.2% of the melanomas overall. BRAF (42.5%), NRAS (15.1%), and CDKN2A (13.2%) were the 3 most common mutations. BRAF and NRAS mutations were more frequent in nodular and superficial spreading melanomas (P < 0.001). Associations with BRAF mutation were as follows: male gender [odds ratio (OR) = 2.4], younger age (OR = 2.7), superficial spreading (OR = 15.6) and nodular melanoma (OR = 9.5), trunk localization (OR = 6.3), and intermittent sun exposure (OR = 4.6). A considerable percentage of V600K (44.4%) mutations were found among the BRAF mutations, whereas KIT mutations (3.8%) were less frequent. Multiple mutations were detected in 13.2% of the melanomas. The most common co-occurrences were in the BRAF, NRAS, and CDKN2A genes. Conclusions: The authors analyzed 10 somatic mutations in the main subtypes of primary cutaneous melanomas from the western region of Turkey. Mutations were found in 64.2% of the melanomas overall. The most common mutations were in the BRAF and NRAS genes. In addition to other less common mutations, a notable number of multiple mutations were encountered. The multiplicity and concurrence of mutations in this study may provide further study areas for personalized targeted therapy.Ege University Scientific Research Fund (BAP)Ege University [2012-TIP-024]Supported by grants from Ege University Scientific Research Fund (BAP, #2012-TIP-024)

BRAF-V600 Mutation Heterogeneity in Primary and Metastatic Melanoma: A Study With Pyrosequencing and Immunohistochemistry

WOS: 000369490000004PubMed ID: 26630683Background:The BRAF-V600 mutation is the most common mutation in cutaneous melanomas and is currently considered a target mutation when planning treatment for metastatic melanoma patients. Various techniques are used to determine the mutation status. The aim of this study was to determine the BRAF-V600 mutation status in primary and metastatic foci of melanoma cases and the consistency between the results of immunohistochemical and molecular methods.Methods:A total of 48 primary or metastatic cases were included in the study. Pyrosequencing was used as the molecular method and the VE1 antibody for immunohistochemical evaluation when determining the BRAF-V600 mutation.Results:The BRAF-V600 mutation was found in 75 of the 96 tumors (78.1%) from the 48 cases. V600E and V600K were present in 60 and 10 tumors, respectively, whereas V600R and V600M were present in 2 tumors and V600G in 1 tumor. There was no mutation in 5 metastases (12.8%) of the 39 cases with a V600 mutation in the primary tumor and no mutation in the primary tumor of 2 of the 36 cases (5.6%) with the V600 mutation in the metastasis. Fifty-six tumors were immunohistochemically positive where a V600E mutation was detected with pyrosequencing. Wild-type tumors (n = 20) and tumors with non-V600E mutations (n = 15) on pyrosequencing were immunonegative with VE1. The sensitivity and specificity of immunohistochemistry were 93.3% and 97.2%, respectively.Conclusions:In conclusion, BRAF-V600 mutation inconsistencies of up to 14.5% can be seen between the primary and metastatic foci in melanoma cases. These findings should be taken into account when planning targeted therapy and deciding on treatment responsiveness/unresponsiveness. An immunohistochemical method can be used as the first step to detect a BRAF-V600 mutation but additional molecular methods should be used when immunohistochemistry results are negative.Ege University Scientific Research Fund (BAP)Ege University [2012-TIP-024]Supported by grants from the Ege University Scientific Research Fund (BAP, #2012-TIP-024)

Atypia and Differential Diagnosis in Cellular Blue Nevi: Clinicopathological Study of 21 Cases

WOS: 000367954000002PubMed ID: 25690862Objective: Cellular blue nevus differs from the classic blue nevus with characteristics such as large size, cellularity, intense pigmentation, and growing pattern with subcutaneous infiltration. It is a dermal melanocytic tumor that can be confused with melanoma due to the atypia it may contain. Material and Method: Hematoxylin-eosin and MIB-1 stained slides of 21 cases diagnosed between 2000-2014 were re-evaluated. In order to attract attention to this rare lesion, 21 cases are presented with the clinical and above-mentioned histopathological findings. Results: Thirteen (61.9%) cases were females and eight (38.1%) were male. The mean age was 25.4 (2-73). The most frequent localization was the sacral and gluteal region (11 cases). The mean diameter was 14.4 mm (4-60 mm). From the parameters defined to assess the atypia, ulceration was identified in four cases. Prominent cellularity and subcutaneous infiltration were seen in three and 16 cases, respectively. Mitosis was seen in six tumors. Immunohistochemically, MIB-1 was present in two cases as 3% and 2% respectively, while in others it was 1% or less. Although there is no precise definition for the "atypical cellular blue nevus", five patients were assessed as atypical cellular blue nevus (a case with infiltrative development of six cm tumor diameter, two cases with two mitosis and a MIB-1 index 3% and 2%, a case with one mitosis and confluent development and a case with one mitosis in addition to focal necrosis areas). No lymph node and/or distant metastasis was observed during follow-up. Conclusion: We think it is more important to rule out the possibility of conventional melanoma in cellular blue nevus with exaggerated morphological findings alongside low proliferative activity rather than to determine the atypia

Perianal fibroadenoma, case report

WOS: 000252515600019PubMed ID: 18212553Extramammary fibroadenomas, occurring in the anogenital region, are rare lesions thought to be arising from "mammary-like anogenital sweet glands" described by van der Putte. We present a 42-year-old woman with a slow-growing, 4-cm, well-circumscribed but nonencapsulated mass in perianal region. The cut surface of the lesion was bulging, gray-white, and slightly lobulated. Microscopically, it was identical to mammary fibroadenoma and composed of concurrent glandular and stromal elements. Low columnar or cuboidal cells with focal, apical cytoplasmic snouts lined the glands, whereas the underlying layer had myoepithelial cell features, expressing smooth muscle actin and S-100. Epithelial component was immunoreactive for human milk fat globulin I. Progesterone receptor positivity was 80%, whereas the estrogen receptor expression was 60%. Gross cystic disease fluid protein and human milk fat globulin 11 were negative. The case is presented to increase the awareness on mammary-like glands of anogenital region, which may give rise to not only fibroadenomas but also fibrocystic disease, phyllodes tumor, carcinoma in situ, invasive carcinoma and lactating adenoma, hidrocystoma, hidradenoma papilliferum, intraductal papilloma, and sclerosing adenosis, although very rare

Description and evaluation of an innovative course on learning and study skills for the first year medical students

WOS: 000241719000007PubMed ID: 17077600The purpose of this study is to share educational structure and evaluation results of an innovative course on effective learning and study skills for the first year medical students. In Turkey, undergraduate medical education takes six years and each year nearly 5,000 high school graduates start medical schools. However, many students experience frustration and failure because of their lack in the learning and studying strategies. At the Ege University Faculty of Medicine, preclinical curriculum consists of the body function systems-based teaching blocks. Year one has three blocks. We implemented an effective learning and study skills course at the first and third blocks of the 2003-2004 curriculum. We evaluated the course by students' feedbacks derived from block questionnaires and students' homework performance analysis. At the first block questionnaire, out of 297, 163 students (54.8%) clearly stated that the course positively influenced their learning process. Structured analysis of the first block's students' homework showed that an average of 206 students (69.3%) can sufficiently describe their learning and studying approach, while 218 (73.4%) can identify the strengths and weaknesses of the curriculum. The average student scores were 74 +/- 10 and 68 +/- 11 out of 100 for first and third blocks, respectively. We interpreted these results as students enjoyed the course and learned the content. In conclusion, a course on effective learning and study skills is likely to assist first year medical students in improving their learning and adaptation to the school

Intestinal Behcet's disease: A case report

WOS: 00024945460064