Classic Kaposi's Sarcoma Research Articles

Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma

BackgroundElectrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years.MethodsA total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12–48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification.ResultsAll KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10−7 to 6.9 × 10−4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No correlation was found between HHV8 subtypes and ECT complete response.ConclusionsECT therapy has a significant effect on HHV8 kinetics in patients with classic KS. The complete remission of patients was accompanied by clearance of circulating virus.

Increased Frequency and Vasculogenic Potential of Endothelial Colony-Forming Cells in Patients with Kaposi’s Sarcoma

Kaposi's sarcoma (KS) is characterized by hyperproliferation of spindle cells that have an endothelial origin and assume their characteristic features upon infection with human herpesvirus-8, the causative agent for KS. The multifocal nature of KS suggests that spindle cells derive from circulating HHV8-infected precursors that yet lack identification. We investigated whether endothelial colony-forming cells (ECFCs) obtained from KS patients may be putative precursors of spindle cells by assessing whether their invitro behavior may evoke the invivo behavior of KS spindle cells. We isolated and cultured ECFCs from the blood of 83 patients with classic KS and compared them with ECFCs obtained from 86 healthy donors. ECFCs were highly increased in the blood of classic KS patients; they showed higher proliferative and vasculogenic potential and higher production of IL-6 than control ECFCs. Similarly to spindle cells in KS lesions, a variable proportion of cells within each ECFC colony expressed the human herpesvirus-8 latency-associated nuclear antigen. ECFCs obtained from classic KS patients evoked KS spindle cell behavior, thus supporting the hypothesis that ECFCs may be putative precursors of spindle cells. ECFCs can therefore represent a noninvasive tool for studying KS and screening drug activity, thus possibly guiding personalized care for KS patients.

Successful Treatment of Classic Kaposi Sarcoma With Long-Pulse Neodymium-Doped Yttrium Aluminum Garnet Laser: A Preliminary Study.

Kaposi sarcoma (KS) is a systemic disease that can present with cutaneous lesions with or without internal involvement, mostly caused by infection with human herpesvirus-8. The treatment options include surgical excision, cryotherapy, radiotherapy, intralesional chemotherapy, laser, and elastic stockings for the prevention of lymphedema. This article presents 7 cases with classic KS treated with the long-pulse neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Forty-nine lesions of 7 KS patients (5 stage 1, 2 stage 2A) were treated with Nd:YAG laser with a spot size of 4 to 6 mm and a fluence of 180 J/cm increased by 10 J/cm in the neighboring area to a maximum of 260 J/cm. The pulse sequencing was 1.5, and delay time was 5 milliseconds. Sessions were continued at 4-week intervals for 2 to 4 sessions. All patients exhibited clinical and histological improvement. One session was sufficient for small lesions, whereas coalescing and multicentric lesions required up to 4 sessions. All the lesions healed in 2 to 4 weeks, with the only complication being mild atrophic scars. With the advantage of penetrating into deeper sites than other lasers, long-pulse Nd:YAG is an efficient and safe local treatment alternative especially for papulonodular and deeper lesions located on bony structures.

The expressions and significance of caspase-3 and E-cad in the tissues of Uygur patients with acquired immunodeficiency syndrome-related and classical Kaposi′s sarcoma in Xinjiang

Objective To further clarify the pathogenesis of different types of Kaposi′s sarcoma (KS) by measuring the protein expressions of caspase-3 and E-cad in tumor tissues of Xinjiang Uygur patients with acqured immunodeficiency syndrome (AIDS)-Kaposi′s sarcoma (KS) and classical KS. Methods From July 2011 to October 2014, 38 patients with KS at the First Affiliated Hospital of Xinjiang Medical University and Urumqi Infectious Disease Hospital were enrolled, among whom 28 were male and 10 were female, and all of them were uygur. Immunohistochemical and Western blot methods were used to detect the expressions of caspase-3 and E-cad proteins in 22 cases of AIDS-KS patients and 16 cases of classic KS. The quantitative data of normal distribution were analyzed by t test, while count data were compared with χ2 test with R × C table. Results KS lesions in patients with classic KS were confined to the skin, without mucosal, lymph node or visceral involvement. Lesions in AIDS-KS patients were not only confined to the skin and superficial lymph nodes, but also oral mucosa involved in 12 cases and internal organs involved in 7 cases. Liver and lung involvement was more common. The CD4+ T lymphocyte count in patients with AIDS-KS was (200.8±166)/μL. All 15 AIDS cases with CD4+ T cell count less than 200/μL developed opportunistic infections.CD4+ T lymphocyte count of patients with classic KS was (562.52±222.66)/μL and the 16 patients with CD4+ T lymphocyte count greater than 350/μL had no opportunistic infections.The results of immunohistochemistry showed that the positive expression rate of caspase-3 protein in KS tissues in patients with AIDS-KS was 68.2%, in patients with classic KS was 100.0%, with significant difference between two groups (χ2=7.37, P=0.01). The positive expression rate of E-cad protein in KS tissues in patients with AIDS-KS was 72.7%, in patients with classic KS was 100.0%, with significant difference between two groups (χ2=5.18, P=0.03). Western blotting showed that the gray value of caspase-3 in the KS tissue of patients with AIDS-KS was 0.55±0.36, and that in patients with classic KS was 0.86±0.56, with significant difference between two groups (t=-2.070, P<0.05). The gray value of E-cad in the KS tissue of patients with AIDS-KS was 0.54±0.41, and that in patients with classic KS was 0.85±0.45, with significant difference between two groups (t=-2.060, P<0.05). Conclusions There are differences in the protein expressions of caspase-3 and E-cad in tumor tissues of patients with AIDS-KS and classical KS in Xinjiang Uygur patients with Kaposi's sarcoma, which may correlate with a faster progression and a higher mortality rate for AIDS-KS. Key words: Acquired immunodeficiency syndrome; Sarcoma, Kaposi; Caspase 3; E-cad

Epigenetic Landscape of Kaposi's Sarcoma-Associated Herpesvirus Genome in Classic Kaposi's Sarcoma Tissues

Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically related to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). It typically displays two different phases in its life cycle, the default latency and occasional lytic replication. The epigenetic modifications are thought to determine the fate of KSHV infection. Previous studies elegantly depicted epigenetic landscape of latent viral genome in in vitro cell culture systems. However, the physiologically relevant scenario in clinical KS tissue samples is unclear. In the present study, we established a protocol of ChIP-Seq for clinical KS tissue samples and mapped out the epigenetic landscape of KSHV genome in classic KS tissues. We examined AcH3 and H3K27me3 histone modifications on KSHV genome, as well as the genome-wide binding sites of latency associated nuclear antigen (LANA). Our results demonstrated that the enriched AcH3 was mainly restricted at latent locus while H3K27me3 was widespread on KSHV genome in classic KS tissues. The epigenetic landscape at the region of vIRF3 gene confirmed its silenced state in KS tissues. Meanwhile, the abundant enrichment of LANA at the terminal repeat (TR) region was also validated in the classic KS tissues, however, different LANA binding sites were observed on the host genome. Furthermore, we verified the histone modifications by ChIP-qPCR and found the dominant repressive H3K27me3 at the promoter region of replication and transcription activator (RTA) in classic KS tissues. Intriguingly, we found that the TR region in classic KS tissues was lacking in AcH3 histone modifications. These data now established the epigenetic landscape of KSHV genome in classic KS tissues, which provides new insights for understanding KSHV epigenetics and pathogenesis.

MDM2 gene polymorphisms and risk of classic Kaposi's sarcoma among Iranian patients.

A single-nucleotide polymorphism (SNP) in the promoter region of MDM2 (SNP309T>G, rs2279744) has been shown to increase the expression of the MDM2 protein in various cancer types. However, only one study has analyzed the role of the MDM2 polymorphism in the development of Kaposi's sarcoma (KS). The association of MDM2 SNP309 with classic KS risk was evaluated in 79 Iranian patients with classic KS and 123 healthy controls. The MDM2 SNP309 was genotyped using PCR and restriction fragment length polymorphism methods. No significant correlation was found between the SNP309 polymorphism in MDM2 promoter and classic KS risk. There was no significant correlation between gender and disease stage. However, a significant association was found between SNP309 GG genotype and younger age (≤50years) (odds ratio 9.5, 95% confidence intervals 1.5-60, p = 0.03). Our findings support no major role for the MDM2 SNP309 in KS development although it might influence the clinical outcome of KS in younger patients.

Localized Kaposi Sarcoma

Kaposi sarcoma (KS) is a lymphoangio-proliferative disease often caused by KS associated herpes virus, also known as human herpes virus 8. There are 4 known variants of KS: Epidemic or AIDS-associated KS, Endemic or African KS, iatrogenic post transplantation KS and Mediterranean or classic KS (CKS). We report a case of CKS treated successfully by radiation therapy.

Classic Kaposi sarcoma in an HIV-negative Han Chinese man: a case report

Kaposi sarcoma (KS) is a multifocal angioproliferativetumor of endothelial origin. Despite nearly identicalclinical and histopathologic presentations, KS isclassified into four distinct varieties: classic/sporadic,AIDS-associated, African/endemic, and iatrogenic. Allsubtypes are invariably linked to human herpesvirus-8(HHV-8) and show a male predilection. Classic Kaposisarcoma is exceedingly rare in the Asian populationand its incidence varies by region and ethnic grouppredominance. A study in the Xinjiang region of Chinafound that only 1% of classic KS cases occurred inpatients belonging to the Han Chinese ethnic group,which formulates 84% of the Taiwanese population.Therefore, classic KS is extremely rare in Taiwan, withvery few reports describing the manifestations ofdisease in this population. We report a case of animmunocompetent 68-year-old HIV-negative HanChinese man born and raised in Taiwan with classicKaposi sarcoma on his trunk and extremities.

HIVNegative Disseminated Cutaneous Kaposi’s Sarcoma: Three Case Reports.

Kaposi’s sarcoma (KS) is a malignant disease that originates from the vascular endothelium and has a very variable clinical course. Classic KS is usually limited the lower extremities and runs a relatively benign, indolent course for 10 to 15 years or more, with slow enlargement of the original tumors and the gradual development of additional lesion; whereas immunodeficiency-related diseases frequently disseminate and involve several organs. Here, we presented three HIV-negative disseminated cutaneous KS cases with different clinical presentations and coexistent diseases.

Bone Involvement in Classic and Agressive Kaposi Sarcoma

Bone Involvement in Classic and Agressive Kaposi Sarcoma

Kaposi's Sarcoma-Associated Herpesvirus: Epidemiology and Molecular Biology.

Kaposi's sarcoma-associated herpesvirus (KSHV), also known as Human herpesvirus 8 (HHV-8), is a member of the lymphotropic gammaherpesvirus subfamily and a human oncogenic virus. Since its discovery in AIDS-associated KS tissues by Drs. Yuan Chang and Patrick Moore, much progress has been made in the past two decades. There are four types of KS including classic KS, endemic KS, immunosuppressive therapy-related KS, and AIDS-associated KS. In addition to KS, KSHV is also involved in the development of primary effusion lymphoma (PEL) and certain types of multicentric Castleman's disease. KSHV manipulates numerous viral proteins to promote the progression of angiogenesis and tumorigenesis. In this chapter, we review the epidemiology and molecular biology of KSHV and the mechanisms underlying KSHV-induced diseases.

Classic and HIV-related Kaposi sarcoma treated with 0.1% topical timolol gel

Classic and HIV-related Kaposi sarcoma treated with 0.1% topical timolol gel

S63 - Treatment of Kaposi's Sarcoma (KS) with nab-paclitaxel

Background: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm that may represent a difficult therapeutic challenge in disseminated stages. Liposomal anthracyclines, or combination chemotherapy are widely used to treat this kind of patients. The efficacy of taxanes (paclitaxel and docetaxel), as agents with antiangiogenic properties, has been described previously in the treatment of KS patients butthe length of the infusion, the need for pre-medication with steroids and toxicity caused by solvents - Cremophor EL (CrEL) and polysorbate 80 (Tween80) - can limit their utilization, especially in elderly patients.Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication which can make it easier to tolerate. At the moment there are no studies on its efficacy and safety in older KS patients. Methods: After written informed consent was obtained a phase II trial was conducted with nab-paclitaxel in 6 patients with advanced-stage KS to assess its safety and antitumor activity. The mean age of patients was 74,8 years( range 71-83). Nab-paclitaxel was administered at a fixed dose of 100 mg intravenously over 30 minutes administered weekly on days 1, 8, and 15 of each 4-week cycle for 4 cycles. No premedication to prevent hypersensitivity reactions was required before administration. Thereafter, if the patient experienced stable disease or better response, treatment doses were given every two weeks until complete disease remission, disease progression, or unacceptable toxicity occurred. Results: All patients improved dramatically after chemotherapy. Partial desinfiltration (n = 2) or complete desinfiltration (n = 4) of all papulonodular skin lesions was observed with marked improvement of lymphedema in 1 patient. Grade 3 neutropenia and thrombocytopenia were observed in three of six and one of six patients, respectively. It was not observed any grade 4 toxicity Conclusions: Classic KS predominantly affects elderly people over 60 years, many of whom do not tolerate aggressive chemotherapy regimens well due to frequent comorbidity and diminished cardiovascular and bone marrow reserves. Nab-paclitaxel has a good and rapid efficacy in our experience which involved a setting of patients difficult to manage.

High Glucose Induces Reactivation of Latent Kaposi's Sarcoma-Associated Herpesvirus

A high prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological conditions of diabetes contribute to KS development. We found elevated levels of viral lytic gene expression when Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells were cultured in high-glucose medium. To demonstrate the association between high glucose levels and KSHV replication, we xenografted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV cells) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high glucose levels induced the production of hydrogen peroxide (H2O2), which downregulated silent information regulator 1 (SIRT1), a class III histone deacetylase (HDAC), resulting in the epigenetic transactivation of KSHV lytic genes. These results suggest that high blood glucose levels in diabetic patients contribute to the development of KS by promoting KSHV lytic replication and infection. IMPORTANCE Multiple epidemiological studies have reported a higher prevalence of classic KS in diabetic patients. By using both in vitro and in vivo models, we demonstrated an association between high glucose levels and KSHV lytic replication. High glucose levels induce oxidative stress and the production of H2O2, which mediates the reactivation of latent KSHV through multiple mechanisms. Our results provide the first experimental evidence and mechanistic support for the association of classic KS with diabetes.

Evaluation of the relationship between c-Kit expression and mean platelet volume in classic Kaposi's sarcoma.

Backgroundc-Kit is a proto-oncogene that encodes tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker, providing information on platelet function and diameter.ObjectiveTo investigate c-Kit expression and intensity in patients with Kaposi's sarcoma (KS) and to investigate the relation between Ki-67 proliferation and MPV.MethodsA total of 32 patients, diagnosed with classic cutaneous KS, were included in this study. We reevaluated the histopathological reports with the preparations, confirmed the diagnosis and then determined the patients' histopathological stages. c-Kit expression and Ki-67 proliferation were investigated immunohistochemically in KS cases, while MPV in all cases was checked.ResultsAlthough c-Kit expression was detected in 22 cases (68.8%), it was not expressed in 10 cases (31.2%). We detected 8 cases with + (25%), 6 with ++ (18.8%) and 8 with +++ (25%). Ki-67 expression was 5.0% (min-max 1.0-20.0). Relapse was observed in 5 cases (15.6%) out of 32. There was positive correlation between c-Kit expression and MPV (rs=0.598, p<0.001), and between c-Kit intensity and MPV (rs=0.588, p<0.001).Conclusionc-Kit is highly positive in KS. c-Kit positivity indicates a high risk of tumor growth, invasion and relapse. Furthermore, c-Kit expression stimulates megakaryocytes to release young and large thrombocytes into the periphery. Thus, high MPV, c-Kit expression and immunostaining intensity indicate high invasion and relapse in KS subjects.

Plasmacytoid dendritic cells in skin lesions of classic Kaposi's sarcoma.

Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n=20) with the control group comprising inflamed MC (n=20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100%). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.

C-Kit, CD34 & α-SMA Immunohistochemical Features in Classic Kaposi Sarcoma and Kaposiform Hemangioendothelioma

Purpose & MethodsThe aim of this work was to study the clinicopathological features of Kaposi sarcoma (KS) & kaposiform hemangioendothelioma (KHE) and analyze their immunohistochemical expression of c-Kit, CD34, α-SMA. The study was performed on cutaneous 10 classic KS & 8 KHE. ResultsKHE shows several dilated lymphatic channels, focal capillary formation, lack of nuclear atypia and mitosis within tumor cells. These features help to exclude Kaposi sarcoma in spite of the kaposiform pattern of tumor cells. C-Kit was expressed by tumor cells in all KHE cases and in 60% only of KS. All elements within both tumor groups expressed CD34 antibody. α-SMA was expressed by tumor cells in 70% of KS cases and none of KHE. ConclusionC-Kit and CD34 seem to be reliable at labeling KS and KHE as they can help in diagnosis of these tumors in routinely processed tissue but they don’t differentiate between them. If α-SMA also labeled the tumor, then KHE diagnosis can be ruled out. KS & KHE exemplify stem cell tumors that could give smooth muscle cell–like phenotype in KS. Anti C-kit therapy should be tested in KS & KHE to prevent recurrence.

Weekly docetaxel in an elderly patient with refractory classic Kaposi sarcoma

Weekly docetaxel in an elderly patient with refractory classic Kaposi sarcoma

Treatment of Classic Kaposi's Sarcoma Showing a Discretely Scattered Distribution with Intralesional Vinblastine Injections

Dear Editor: Classic Kaposi's sarcoma (CKS) is one of clinical types of Kaposi's sarcoma (KS)1,2. Treatment options for CKS vary depending on clinical features such as age, number and distribution of lesions, and tumor depth3. It is essential, therefore, that treatment is tailored to the individual. Although many therapeutic strategies from systemic to local treatments are available for CKS, those treatments tend not to be suitable for cases with a discretely scattered distribution. Therefore, we report on a case of discretely scattered CKS treated successfully with intralesional vinblastine injections, which have previously proved effective and well-tolerated in acquired immune deficiency syndrome-related patients with localized oral KS lesions4. A 58-year-old Korean woman presented with a 5-year history of a skin lesion on her chin. Since that time of the initial skin lesion having appeared, subsequent lesions developed slowly on the upper and lower extremities. The patient was immunocompetent. Her past medical history was unremarkable except for the use of medication for dyslipidemia. A physical examination revealed multiple non-tender, round to elongated, red-purple papules and plaques (Fig. 1A), scattered over the chin, right hand, left forearm, and left shoulder. A skin biopsy of the chin was performed with immunohistochemistry stains (Fig. 2). Laboratory test results, including a complete blood cell count, thyroid function test, and anti-human immunodeficiency virus test, were all reported within normal limits. There was no evidence of metastasis on chest or abdominal computed tomography or on total body positron emission tomography imaging. We diagnosed this case as a discretely scattered CKS without visceral involvement. Although the patient had multifocal lesions on the head and limbs, the total number and size of the lesions had not changed in the last 3-months. To minimize the complications and considerable toxicities associated with the use of systemic chemotherapy or radiotherapy, we opted to treat our patient with intralesional vinblastine administration instead. All skin lesions were treated with intralesional vinblastine injections at a dose of 0.1 mg/cm2 using a 0.1 mg/ml solution of vinblastine sulfate in sterile saline4. After 5 weeks of treatment the tumors had completely regressed with no significant side effects except for a slight postinflammatory hyperpigmentation response (Fig. 1B). The patient was kept on regular follow-up and showed no signs of recurrence of CKS 6-months after treatment. Fig. 1 Clinical presentation of a discretely scattered classic Kaposi's sarcoma. (A) Widely distributed red-purple papules and plaques evident before treatment, and (B) complete regression of the tumors 5 weeks after treatment with intralesional vinblastine ... Fig. 2 Immunohistochemical evaluation of classic Kaposi's sarcoma specimens. (A) Endothelial cells of the abnormal vessels staining positively for cluster of differentiation 31; (B) Spindle cells staining positively for Friend leukemia virus integration-1; and ... CKS is usually indolent over many years but is not life threatening5. Consequently, clinicians have often hesitated in administering systemic therapy, which decreases quality of life, in patients with discretely scattered CKS. Our patient exhibited a dramatic response without serious side effects after a single cycle of intralesional vinblastine injections and had no additional lesions under outpatient follow-up. We conclude, therefore, that intralesional vinblastine administration is one of the most effective and useful treatment alternatives for relatively stable, discretely scattered CKS. However, the 6-month follow-up may not be sufficiently long when we consider the growth pattern of CKS and the potential for occult CKS lesions caused by hyperpigmentation, which were not histologically confirmed but need to be considered in estimating patient responses following intralesional vinblastine injections.

Association of genetic variations in miR-146a rs2910164 and miR-149 rs11614913 with the development of classic Kaposi sarcoma.

Classic Kaposi sarcoma is a type of vascular proliferative inflammatory disease. Previous studies have reported significant associations between microRNAs expression and the development of classic Kaposi sarcoma. Here, we conducted a case-control study to investigate the association between miR-146a and miR-149 genetic polymorphisms and risk of classic Kaposi sarcoma in a Chinese population. Both classic Kaposi sarcoma patients and healthy controls were recruited between December 2013 and October 2015. Genotyping of miR-146a and miR-149 was performed by polymerase chain reaction-coupled with restriction fragment length polymorphism. Results showed that the GG genotype of miR-146a was associated with increased risk to classic Kaposi sarcoma (OR = 6.00, 95%CI = 1.19-30.12), as compared with the CC genotype. In the recessive model, we found that the GG genotype carried a 4.55-fold increased risk to classic Kaposi sarcoma as compared with the CC + CG genotype (OR = 2.06, 95%CI = 1.04-20.29). In conclusion, our study demonstrated that miR-146a, but not miR-149 polymorphism, is associated with risk to classic Kaposi sarcoma in the Chinese population.