A prospective pilot study on the effects of endoscopic sinus surgery on upper and lower airway performance.

OBJECTIVE: The relationship between chronic rhinosinusitis, asthma and allergic rhinitis is well known, but only recently has the scientific community started to evaluate these as different manifestations of a common pathogenic phenomenon, considering them as a unified airway disease. METHODS: Twenty-two patients with chronic rhinosinusitis treated with endoscopic sinus surgery (ESS) were included in the study. Sino-nasal assessment questionnaire (SNAQ) investigating subjective evaluation of sino-nasal state was administered to patients, while objective evaluations included nasal endoscopy, sinonasal CT, skin prick tests, nasal cytology, spirometry, bronchodilator responsiveness testing and sputum eosinophil count. All tests were performed before surgery. Two months after surgery, SNAQ questionnaire, nasal endoscopy, spirometry and bronchodilator responsiveness testing were repeated. RESULTS: All patients had significant improvement of subjective status: mean SNAQ score decreased in all from 99.31 to 16.04. Mean Forced Expiratory Volume in the 1st second (FEV1) significantly improved after surgery from 3.23 to 3.45 L/s. CONCLUSIONS: ESS achieved a beneficial effect on upper and lower airway status in patients with chronic rhinosinusitis with or without lower airway diseases.

Whole-exome Sequencing of Prostate Cancer in Sardinian Identify Recurrent UDP-glucuronosyltransferase Amplifications.

Globally, prostate cancer is the third most common cancer in the world, and the second most common cancer in men. However, rates for incidence and mortality vary considerably with race, ethnicity, and geography. Over 97 significantly mutated genes that have been identified in prostate cancer; however, a lack of genomic prostate cancer studies focusing on different racial and ethnic groups and racial mixing pose a serious challenge to universalize these findings. The Sardinian population is an isolated Mediterranean population that has a high frequency of centenarians and a much lower incidence of prostate cancer than found in males in mainland Europe. Here, we conducted a genomic prostate cancer study on a Sardinian cohort diagnosed with local prostate cancer. Our data reveals a low rate of ERG fusion in Sardinian prostate cancer. Interestingly, we identified a novel BTBD7-SLC2A5 fusion that occurred in 13% of the patients. We also found that the UGT2B4 on 4q13.2 was amplified in 20% of the Sardinian patients but rarely amplified in patients of other population. These observations underscore the importance of the inter-population molecular heterogeneity of prostate cancer. In addition, we examined the expression of UGT2B4 in 497 prostate cancer patients derived from The Cancer Genome Atlas database. We found that high expression of UGT2B4 was associated with low-grade prostate cancer and upregulation of UGT2B4 in tumors was associated with upregulation of metabolism pathways such as 'de novo' IMP biosynthetic process, glutamine and monocarboxylic acid metabolism. These data provide insight into clinical relevance and functional mechanism of UGT2B4. Further understanding functional mechanism of UGT2B4 amplification and BTBD7-SLC2A5 fusion will aid in developing drugs to benefit the prostate cancer patients.

Italian observational study on HPV infection, E6, and p16 expression in men with penile cancer.

BACKGROUND: Human Papillomavirus (HPV) infection is one of the most important causes of cancer. It can play a role in cervical and extra-cervical cancers. Penile cancer is rare, even if an increasing trend was recently reported. Aim of the present study was to assess the prevalence and distribution of HPV genotypes in cases of penile cancer diagnosed in Sardinia, Italy. Surrogate markers of HPV infection (i.e., E6 and p16 genes) were also evaluated in all cases. METHODS: An observational, retrospective study which recruited all cases of penile cancer diagnosed between 2002 and 2019 at a tertiary care hospital in Sardinia, Italy, was carried out. HPV-DNA detection and genotyping were performed by Real-time PCR. Specimens were tested for oncogene E6 mRNA and for p16(INK4a) expression. RESULTS: HPV prevalence was 28.1% (9/32); HPV-16 was the most prevalent genotype (7/9, 77.8%). p16INK4a positivity was found in 66.7% of the samples with a statistically significant difference between HPV-positive and -negative groups. E6-transcript was detected in 71% of the HPV-16 positive samples. The overall survival was not statistically different between HPV-positives and -negatives. DISCUSSION: The present study confirms the etiologic role of HPV in penile cancer and supports the adoption of vaccination strategies in men and women. Further studies should clarify the diagnostic and prognostic role of E6 and p16 proteins. CONCLUSION: HPV infection can favor the occurrence of penile cancer, whose diagnosis and prognosis could be improved with the implementation of validated molecular techniques.

Distribution of HPV Genotypes in Patients with a Diagnosis of Anal Cancer in an Italian Region.

Objectives: Anal cancer is a rare disease. However, its incidence is increasing in some population groups. Infection caused by Human Papillomavirus (HPV) is strongly associated with the risk of anal cancer, whose variability depends on samples, histology, and HPV detection methods. The aim of the study was to assess prevalence and distribution of HPV genotypes in patients diagnosed with anal carcinoma. Methods: An observational, retrospective study was carried out in a tertiary care hospital in North Sardinia, Italy. Specimens of anal cancer diagnosed from 2002-2018 were selected. Demographic, epidemiological, and clinical variables were collected to assess their relationship with the occurrence of anal cancer. Results: The overall HPV positivity was 70.0% (21/30), with HPV-16 being the predominant genotype (~85%). The highest prevalence of anal cancer was in patients aged ≥55 years. HPV positivity was higher in women (p-value > 0.05) and in moderately differentiated samples (G2) (p-value < 0.05). p16INK4a and E6-transcript positivity were found in 57% and 24% of the HPV positive samples, respectively. The OS (overall survival) showed a not statistically significant difference in prognosis between HPV positive sand negatives (10, 47.6%, vs. 4, 44.4%; p-value = 0.25). Conclusions: HPV-DNA and p16INK4a positivity confirmed the role of HPV in anal carcinoma. Our findings could support the implementation and scale-up of HPV vaccination in males and females to decrease the incidence of HPV-associated cancers. Further studies are needed to better clarify the prognostic role of HPV/p16 status.

Primary extranodal vaginal non-hodgkin lymphoma: Diagnostic pitfalls and therapeutic challenges.

INTRODUCTION: Primary extranodal non-hodgkin vaginal lymphoma (PeNHVL) represents a rare entity, with few data published until now. We present here a series of patients with PeNHVL, analyzing our data as part of a detailed review of the available literature. METHODS: The study included a consecutive series of 6 patients with final diagnosis of PeNHVL admitted at our Institution between January 2000 and December 2017. The systematic review was conducted according to PRISMA guidelines. A literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed using the following terms: 'vaginal lymphoma'. Relevant data were collected and analyzed for the purposes of this study, reporting results through a narrative approach. RESULTS: In our series discomfort and vaginal pain, refractory to medical treatments represent the symptoms of disease presentation, and the presence of localized/diffused anelastic area in the vaginal wall with tactile sensation of cork emerges as diagnostic sign (Cork Wall sign). The literature revision included 41 studies, with an overall population of 74 patients. The vast majority of women were diagnosed as early stage disease (93.6%) and received chemotherapy (74.6%) with a very high response rate (96%). Death from disease occurred in 5 women (6.7%). CONCLUSIONS: Localized or diffused hard-ligneous vaginal areas with Cork Wall sign represent the typical sign of disease presentation. PeNHVL is characterized by a very high sensitivity to chemotherapy and very favourable prognosis; therefore, radical surgery is not indicated. Histotype characterization is crucial to identify those uncommon variants associated with a less favorable clinical outcome.

Intrahepatic bile duct primary cilia in biliary atresia.

AIM: The etiopathogenesis of non-syndromic biliary atresia (BA) is obscure. The primary aim was to investigate intrahepatic bile duct cilia (IHBC) in BA at diagnosis and its correlation with clinical outcome. The secondary aim was to analyze IHBC in routine paraffin-embedded liver biopsies using conventional scanning electron microscopy (SEM). METHODS: Surgical liver biopsies taken at diagnosis from 22 BA infants (age range, 39-116 days) and from eight children with non-BA chronic cholestasis (age range, 162 days -16.8 years) were evaluated for IHBC by immunofluorescence (IF) and SEM. A minimum 18-month follow-up after surgery was available for all patients. RESULTS: By IF, cilia were present in 6/8 (75%) non-BA but only in 3/22 (14%) BA cases, and cilia were reduced or absent in 19/22 (86%) BA and 2/8 (25%) non-BA livers (P < 0.01). In BA, cilia presence was found to be associated with clearance of jaundice at 6-month follow-up (P < 0.05). However, high overall survival rates with native liver, >90% at 12 months, and >70% at 24 months post-surgery, were recorded regardless of cilia presence/absence at diagnosis. Electron microscopy was able to detect bile ducts and cilia in routine liver biopsies, revealing significant abnormalities in 100% BA livers. CONCLUSIONS: The presence of IHBC in BA livers at the diagnosis was associated with resolution of cholestasis, although was not predictive of short-term survival with native liver. Scanning electron microscopy represents a powerful new tool to study routine liver biopsies in biliary disorders. Cilia dysfunction in BA pathogenesis and/or disease progression warrants further investigation.

Female Adnexal Tumors of Probable Wolffian Origin (FATWO): A Case Series With Next-Generation Sequencing Mutation Analysis.

Female adnexal tumors of probable Wolffian origin are rare gynecologic tumors with <90 cases reported in the current scientific literature. Their clinical features have been described extensively; less is known about the pathophysiological mechanisms and the molecular alterations underlying their development and growth. We performed a complete histopathologic examination and a systematic mutation analysis using a next-generation sequencing approach on 3 female adnexal tumors of probable Wolffian origin from the archives of our institution to detect possible genetic alterations and to explore their role in the development of these rare tumors. The 3 cases contained missense mutations in different genes belonging to distinct molecular pathways: CTNNB1 and MET mutations for the first case, PIK3CA for the second one, and BRAF and CDKN2A for the third one. Two variants with an unknown functional effect on the protein were found in KDR and TP53 genes. In conclusion, genetic heterogeneity was found in our series. No constant involvement of the most common pathways involved in tumorigenesis was found; nevertheless, further studies are necessary to confirm the results of this pilot study.

Long non-coding RNA CASC2 in human cancer.

Long non-coding RNAs cover large part of the non-coding information of the human DNA, which represents more than 90% of the whole genome. They constitute a wide and complex group of molecules with more than 200 nucleotides, which generally lack an open reading frame, and are involved in various ways in the pathophysiology of cancer. Their roles in the regulation of gene expression, imprinting, transcription, and post-translational processing have been described in several types of cancer. CASC2 was discovered in 2004 in patients with endometrial carcinoma as a potential tumor suppressor. Since then, additional studies in other types of neoplasia have been carried out, and both mechanisms and interactions of CASC2 in cancer have been better elucidated. In this review, we summarize the current knowledge on the role of CASC2 in the genesis, progression, and clinical management of human cancer.

Vitamin D status and risk for malignant cutaneous melanoma: recent advances.

Cutaneous malignant melanoma, whose incidence is increasing steadily worldwide, is the result of complex interactions between individual genetic factors and environmental risk factors. Ultraviolet radiation represents the most important environmental risk factor for the development of skin cancers, including melanoma. Sun exposure and early sunburn during childhood are the principal causes of cutaneous melanoma insurgence in adults, with double the risk relative to a nonexposed population. Consequently, ultraviolet protection has long been recognized as an important measure to prevent such a malignancy. Biological and epidemiological data suggest that vitamin D status could affect the risk of cancer and play a role in cancer prevention by exerting antiproliferative effects. Solar radiations are critical for vitamin D synthesis in humans; however, uncontrolled and intensive sun exposure is dangerous to skin health and may contribute toward the development of cutaneous malignant melanoma. An optimum balance between sun protection and exposure is thus advocated. Additional research is required to confirm the preventive role of vitamin D in melanoma incidence or a positive influence on patient outcome.

Epidemiology and genetic susceptibility of malignant melanoma in North Sardinia, Italy.

The aim of this report was to study the descriptive and genetic epidemiology of malignant melanoma in North Sardinia, Italy, in the period 1992-2011. Epidemiological data were obtained from the local tumor registry, which is part of the Italian Association for Tumor Registries. Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes. The overall number of cases registered was 532. The male-to-female ratio was 1 : 1 and the mean age was 56 years for men and 55 years for women. The standardized incidence rates were 4.9/100 000 and 4.4/100 000 and the standardized mortality rates were 1.7/100 000 and 1.3/100 000 for men and women, respectively. The relative 5-year survival was 77% for men and 79% for women. In our series, 24/316 (7.6%) patients had a familial occurrence of melanoma (presence of at least one additional family member affected). Among these, one variant (Gly23Asp), reported previously as a low-frequency disease-causing mutation, was detected by mutational screening in the p16 gene only. With the exception of polymorphisms, none of either the sporadic melanoma patients or healthy controls presented a germline mutation in candidate genes. An increase in incidence and a decrease in mortality rates of malignant melanoma were registered in North Sardinia, from 1992 to 2011, whereas survival was similar to that reported in recent international reports. The high-penetrance melanoma susceptibility genes (CDKN2A and CDK4) are not involved in predisposition to melanoma in North Sardinia.

Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.

BACKGROUND: Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population. METHODS: A total of 1284 Sardinian patients with histologically-proven diagnosis of colorectal carcinoma (CRC) and presenting with metastatic disease were included into the study. Genomic DNA was isolated from formalin-fixed, paraffin-embedded primary tumour tissue samples of CRC patients and screened for mutations in RAS and BRAF genes, using pyrosequencing assays, and in PIK3CA gene, using automated DNA sequencing assays. RESULTS: Overall, mutation rates were 35.6 % for KRAS, 4.1 % for NRAS, and 2.1 % for BRAF. Among available DNA samples, 114/796 (14.3 %) primary CRCs were found to carry a mutation in the PIK3CA gene. In this subset of patients analysed in all four genes, a pathogenetic mutation of at least one gene was discovered in about half (378/796; 47.5 %) of CRC cases. A mutated BRAF gene was found to steadily act as a negative prognostic factor for either time to progression as metastatic disease (from detection of primary CRC to diagnosis of first distant metastasis; p = 0.009) or partial survival (from diagnosis of advanced disease to the time of death or last control; p = 0.006) or overall survival (p < 0.001). No significant impact on prognosis was observed for mutated KRAS, NRAS, and PIK3CA genes or combined RAS mutations (all RAS). CONCLUSIONS: Our study defines both prevalence and prognostic role of main activated oncogenes in a population-based large collection of CRC patients.

Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.

BACKGROUND: Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. METHODS: We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. RESULTS: Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. CONCLUSIONS: This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population.

KRAS mutational concordance between primary and metastatic colorectal adenocarcinoma.

KRAS mutation analysis is commonly performed on tissue samples obtained from primary colorectal cancers (CRCs). The metastatic lesions of CRC are usually considered as qualitatively similar or even identical to the primary tumors. The aim of this study was to evaluate the spectrum and distribution of KRAS mutations in a large collection of CRCs, while also evaluating the concordance of primary and metastatic lesions among available paired specimens from the same patients. A total of 729 patients with histologically confirmed advanced CRC at the University Hospital and Local Health Unit (Sassari, Italy) were included. Clinical and pathological features were obtained from medical records and/or pathology reports. Formalin-fixed, paraffin-embedded tissue samples were used for mutation analysis. Genomic DNA was isolated using a standard protocol; the coding sequence and splice junctions of exons 2 and 3 in the KRAS gene were screened by direct automated sequencing. Overall, 219 (30%) KRAS mutations were found; 208 (30.1%) were identified in the 690 primary tumors and 11 (28.2%) in the 39 metastatic tissue samples. Among the 31 (4.3%) patients who had paired samples of primary CRC and synchronous or asynchronous metastases, 28 (90.3%) showed consistent mutation patterns between the primary tumors and metastatic lesions. In one case, an additive mutation (Q61L) was found in the metastatic tissue, while two other discrepant cases exhibited a different mutation distribution; Q61H in the primitive lesion and G13V in the metastatic lesion in one case, and a mutated primary tumor (Q61L) and wild-type metastasis in another case. The results of this study confirm that a high concordance exists between the results of KRAS mutation analysis performed in primitive and metastatic CRCs; independent subclones may be generated in a limited amount of patients.

Triple-negative breast cancer frequency and type of BRCA mutation: Clues from Sardinia.

Germline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the risk of developing breast cancer. Among the prognostic factors currently used in clinical practice, the disease stage and the receptor status play a crucial role in the management of breast carcinoma. Triple-negative breast cancer (TNBC) has been classified as a disease subgroup that is negative for oestrogen, progesterone and HER2 receptor expression, and presents a poor prognosis. The present study investigated the correlation between BRCA1/2 mutations and TNBC status in a large series (n=726) of breast cancer patients from Sardinia. The BRCA mutation screening was performed on genomic DNA from peripheral blood samples by denaturing high-performance liquid chromatography analysis and automated DNA sequencing. Overall, 21/726 (2.9%) patients carried a germline mutation in BRCA1 or BRCA2. The TNBC phenotype was significantly associated with the BRCA1 mutations (P<0.001), whereas no association was found with the BRCA2 mutations (P=0.837). With respect to patient origin within Sardinia, a significant inverse distribution of mutations was found; BRCA1 and BRCA2 mutations represented 86 and 93% of the mutated cases in Southern and Middle-Northern Sardinia, respectively (P<0.001). Patients from the geographical area with BRCA1 mutation prevalence presented a TNBC incidence much higher than that observed in cases from the area with BRCA2 mutation prevalence (12 vs. 4%, respectively; P=0.037). These findings further confirmed that the occurrence of TNBC is significantly associated with the BRCA1 mutation carrier status and that a different 'genetic background' may have a phenotypic impact in the onset of breast cancer.

Epidemiology of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy). A population-based report.

UNLABELLED: The aim of this population-based study was to analyze and describe the epidemiological characteristics and trends of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy), in the period 1992-2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. The overall number of malignant pleural mesothelioma cases registered was 70. The male-to-female ratio was 4:1 and the mean age 65.1 years for males and 63.4 years for females. The standardized incidence rates were 1.2/100,000 and 0.3/100,000 and the standardized mortality rates 0.6/100,000 and 0.2/100,000 for males and females respectively. A trend to increase in incidence in recent years was evidenced. This trend seems to follow the general national tendency and it depends on a large diffusion of asbestos usage in the past, delayed legislative interventions and probably a cleaning strategy of residual contamination fonts to intensify. The relative 5 years survival was low, suggesting the necessity to further intensify research and cure methods for the treatment of this extremely aggressive disease. KEY WORDS: Asbestos exposure, Mesothelioma, Pleura, Sassari.

Estimates of cancer burden in Sardinia.

AIMS AND BACKGROUND: Cancer registration in Sardinia covers 43% of the population and started in 1992 in the Sassari province. The aim of this paper is to provide estimates of the incidence, mortality and prevalence of seven major cancers for the entire region in the period 1970-2015. METHODS: The estimates were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Estimates were compared with the available observed data. RESULTS: In 2012 the lowest incidence was estimated for stomach cancer and melanoma among men, with 140 and 74 new cases, respectively, per 100,000. The mortality rates were highest for lung cancer and were very close to the incidence rates (77 and 95 per 100,000, respectively). In women, breast was by far the most frequent cancer site both in terms of incidence (1,512 new cases) and mortality (295 deaths), followed by colon-rectum (493 cases and 201 deaths), lung (205 cases and 167 deaths), melanoma (106 cases and 15 deaths), stomach (82 cases and 61 deaths), and uterine cervix (36 cases and 19 deaths). The highest prevalence was estimated for breast cancer (15,180 cases), followed by colorectal cancer with about 7,300 prevalent cases in both sexes. CONCLUSION: This paper provides a description of the burden of the major cancers in Sardinia until 2015. The comparisons between the estimated age-standardized incidence rates and those observed in the Sassari registry indicate good agreement. The estimates show a general decrease in cancer mortality, with the exception of female lung cancer. By contrast, the prevalence is steeply increasing for all considered cancers (with the only exception of cancer of the uterine cervix). This points to the need for more strongly supporting evidence-based prevention campaigns focused on contrasting female smoking, unhealthy nutrition and sun exposure.

AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells.

The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals.

Unexpected distribution of cKIT and BRAF mutations among southern Italian patients with sinonasal melanoma.

BACKGROUND: Racial and geographic factors seem to affect the incidence of cutaneous and mucosal melanoma. OBJECTIVE: To investigate the occurrence of BRAF and cKIT impairments in patients with sinonasal melanoma in Southern Italy. METHODS: Eleven sinonasal melanomas were screened for BRAF mutations and cKIT alterations by immunohistochemistry (CD117), fluorescence in situ hybridization and sequencing analyses. RESULTS: A high prevalence (4/11; 36%) of BRAF mutations and lack of cKIT mutations were observed. Amplification of cKIT was found in 18% of cases; cKIT expression was detectable in 18% non-overlapping cases. No correlation between CD117 and cKIT alterations was observed. One (6%) cKIT and two (12%) BRAF mutations were detected in an additional series of 17 acral/mucosal melanomas from the same geographic areas. CONCLUSION: Mutations of cKIT are infrequent in sinonasal melanoma in Southern Italy.