Classic Kaposi's Sarcoma Research Articles

Italian guidelines for the diagnosis and treatment of classic and iatrogenic Kaposi's sarcoma

Kaposi's sarcoma (KS) is a lymphangioproliferative disorder associated with human herpesvirus 8 (HHV8) infection. Four clinical subtypes are recognized: classic, endemic, epidemic (HIV-related) and iatrogenic. KS diagnosis is based on clinical features, histopathological assessment, and HHV8 serology. Classic KS is usually skin-limited and has a chronic course, while the iatrogenic variant may show mucosal, nodal or visceral involvement. Clinical staging is fundamental to guide the management. Localized disease may be treated with different local therapies, even if there are no randomized trials comparing these different modalities. Aggressive, disseminated KS and cases with visceral involvement usually require systemic chemotherapy, most commonly vinblastine, bleomycin or paclitaxel. Iatrogenic KS needs immunosuppression tapering/withdrawal and, if possible, switch to m-TOR inhibitors in post-transplant KS. The present work by a panel of Italian experts provides guidelines on KS diagnosis and management based on a critical review of the literature and a long and extensive personal experience.

A comparative study of classic and HIV-viremic and aviremic AIDS Kaposi sarcoma.

Kaposi sarcoma in people living with HIV (PLHIV) is the most common AIDS-associated malignancy. There is increased interest in Kaposi sarcoma in PLHIV with controlled HIV viremia. To describe Kaposi sarcoma occurring in PLHIV despite virological control and to compare their clinical presentations with viremic AIDS-Kaposi sarcoma (AIDS-KS) and classic Kaposi sarcoma (CKS). This was a monocentric retrospective study, including all Kaposi sarcoma patients registered between the 1 January of 2000 and 31 December 2017 in a comprehensive data bank for all cancers in the Hérault region, South of France. AIDS-KS were also described using chart reviews from the Infectious diseases Department, which followed more than 90% of PLHIV from the same region. We defined aviremic AIDS-KS as Kaposi sarcoma occurring in persons taking HAART with a HIV viral load less than 50 copies for more than 12 months. We compared clinical characteristics of persons with aviremic AIDS-KS, viremic AIDS-KS and CKS, using the Kriegel score and number and topography of skin lesions, and presence of lymphedema. We retrieved 187 Kaposi sarcoma cases, of which 12 occurred in PLHIV with aviremic AIDS-KS. Kriegel score stage I was found in 10 (83%) of the aviremic AIDS-KS, 34 (68%) of CKS and 38 (58.4%) of viremic AIDS-KS cases, with similar clinical presentations between aviremic AIDS-KS and CKS groups, and viremic AIDS-KS persons having more aggressive presentations. One person with aviremic AIDS-KS had visceral involvement. We showed that Kaposi sarcoma in PLHIV with controlled viremia were generally indolent, similarly to CKS. Visceral involvement is, however, possible.

Classic Kaposi Sarcoma from North-East India: A case report

Kaposi sarcoma (KS) is a low-grade vascular neoplasm caused by proliferation of lymphatic endothelium associated with human herpes-8 (HHV-8) infection. An 81-year-old male presented with 1-year history of multiple brownish papular lesions on lower limbs. He gave no history of high risk behaviour or treatment with immunosuppressants. Cutaneous examination revealed bluish-black discrete papules, small nodules and non-pitting edema on lower limbs, and large ulcerative plaques on left foot. Mucous membranes, lymph nodes and systemic examination were normal. Histopathological examination of the papular lesions showed spindle cell proliferation and vascular slits with extravasated red blood cells. Human immunodeficiency virus (HIV) serology was negative. However, total lymphocyte and absolute CD4+ T lymphocytes counts were reduced. We report this case of Classic Kaposi sarcoma (CKS) because of it’s rarity in India as well as being the first report from Northeast India, indicating wide ethnic and geographical distribution of this condition.

1077MO PD1 blockade with pembrolizumab in classic and endemic Kaposi sarcoma: A multicenter phase II study

While the treatment of iatrogenic and HIV-related KS is well defined, mostly based on restoring the immune function, the treatment of classic/endemic KS is less codified. Chemotherapy or interferon are used for patients (pts) with extensive cutaneous and/or visceral KS but the tolerance may be poor in elderly pts, and long-term remissions are rare. Major efficacy of PD1 blockade has been demonstrated in Merkel cell carcinoma, another virus-induced tumor, in part driven by the immunogenicity of virus-associated antigens.

A phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (CKS).

11518 Background: CKS is a mesenchymal neoplasm associated with HHV8 infection. Though recombinant INFa is approved for treatment of AIDS-related KS, data is limited regarding the role of immune modulation in CKS therapy. Based on favorable responses in viral-induced cancers, we hypothesized that CTLA-4 and PD-1 blockade can induce tumor regression in CKS. We present pre-planned interim analysis of a phase II study of Nivo/Ipi in previously treated progressive CKS. Methods: CKS pts with progressive disease after > 1 line of systemic therapy and measurable disease received nivolumab 240mg d1,15,28 and ipilimumab 1mg/kg d1 q42 days until progression or toxicity. The primary endpoint was overall response rate (ORR) evaluated clinically, radiologically (RECIST) and metabolically (FDG-PET). Secondary endpoints include 6-months progression free survival rate (PFS) and safety. Exploratory endpoints included PD-L1/MMR by IHC, DNAseq (596 genes)/RNAseq (whole transcriptome) of tumor and matched blood specimens to explore CKS genomic traits and IO correlates: TMB and MSI status, MMR and PD-L1 protein expression, and immune gene transcript expression (PD-1, PD-L1, CTLA-4, and others) (Tempus Labs, Chicago, IL, USA). Results: Fifteen patients were enrolled and evaluable (Apr18-Jan20). Median age 72.5 (61-81), all male. At a median FU of 15.7 mo ORR as per RECIST was 66% (9 pts PR, 1 pt CR, 2 pts SD, 3 pts NE). Clinical ORR was 87% and metabolic ORR was 60%. Median PFS was not reached, 6mo PFS rate was 85% and 1y PFS rate was 75%. The safety profile was as expected with all pts experiencing G1 toxicity, 3 pts with G2 toxicity (1 hepatic, 2 asymptomatic lipase increase) and 2 pts with G3 toxicity (1 colitis, 1 asymptomatic lipase increase). One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in 3 pts. Correlative results are available for 8 pts showing a trend for copy number loss in genes with tumor-suppressive activity (FOXA1, ELF3), no PDL1 expression, low TMB, microsatellite stability, but marked overexpression of CTLA-4, PD-1, PDL-1, CD40, OX40 and LAG3 RNA immune transcripts. Conclusions: The interim analysis of this prospective phase II study of nivolumab and low-dose ipilimumab demonstrates promising activity in progressive CKS, with 66% ORR and a 6mo PFS rate of 85%. Toxicity profile is as expected in this class of drugs. Correlative studies are preliminary, but warrant further investigation into genomic traits and immune gene expression profiles. Clinical trial information: NCT03219671. Clinical trial information: NCT03219671 .

Nodular Classic Kaposi's Sarcoma Treated With Neodymium‐Doped Yttrium Aluminum Garnet Laser Delivered Through a Tilted Angle: Outcome and 12‐Month Follow Up

Classic Kaposi's sarcoma (KS) is a multifocal angioproliferative disorder with a long and indolent course typically affecting the lower extremities of elderly men. Multiple nodules with a rapid growth may sometimes develop, causing pain, bleeding, and discomfort on walking. In such cases, immediate intervention using different methods, including laser therapy, is advisable. We report our experience in classic KS patients with the use of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser delivered through a tilted angle. A total of 81 KS nodules (0.5-3 cm size) located in the feet or lower limbs of nine patients (mean age: 78.8 years; age range: 64-86 years) were selected for treatment with Nd:YAG laser (5-7 mm spot, 140-200 J/cm2 fluence, 5 ms triple pulse with 10 ms delay). The laser beam was delivered at the periphery of each nodule using a tilted angle of 30° to 60° according to lesion size in order to better target the feeding vessels located in the inner and basal depth of the lesion and minimize tissue damage. The treatment outcome was evaluated by clinical photograph, videodermatoscopy, and ultrasound scanning performed before and after treatment, and at each monthly follow-up visit. All treated patients showed full recovery, with negligible scarring, no residual hyperpigmentation, and complete regression of pain. Treatment discomfort was minimal and use of topical anesthetics was not needed. No recurrences were observed at 12-month follow up. Long-pulse Nd:YAG laser delivered using a tilted angle is a fast, easy, effective, comfortable, and safe treatment option available to promptly shrink bulky, painful, or bleeding nodules with minimal discomfort and gives excellent functional and cosmetic results. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Bone involvement in classic Kaposi's sarcoma.

Classic Kaposi's sarcoma (KS) is a rare angioproliferative neoplasm which typically occurs on the skin of the lower limbs of immunocompetent elderly men. Bone involvement in classic KS has been exceptionally reported. To identify patients with classic KS who developed bone involvement based on a retrospective analysis of our departmental database. Clinical presentation, diagnostic method, treatment, and outcome were analysed and compared with cases reported in the literature. In total, we identified 1,196 patients with classic KS, three (0.25%) of whom developed bone involvement. The patients were all male and the average age at onset of bone involvement was 81.3 years. All three patients had biopsy-proven anaplastic KS affecting a bone of the lower limb. Bone radiological features were non-specific in one patient, while in all patients magnetic resonance imaging revealed osteolytic lesions and/or a solid tumour. HHV8 genotype analysis was performed in two patients, and subtypes A and C were found. Bone involvement should be considered in patients with known KS presenting with bone pain.

Expression of Programmed Cell Death Proteins in Kaposi Sarcoma and Cutaneous Angiosarcoma.

Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory patients with classic Kaposi sarcoma (CKS) and human immunodeficiency virus (HIV)-associated Kaposi sarcoma (HIV-KS) there is a high need for more effective treatment modalities. The aim of this work was to study programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) protein expression and related immune parameters in CKS, HIV-KS, and CAS and correlate it with other immunologic parameters and clinical data. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tumor tissue of 19 CKS, 7 HIV-KS, and 12 CAS patients using antibodies against the following (and they are): PD-1, PD-L1, CD4, CD8, CD56, and FOXP3. PD-1 expression significantly correlated with PD-L1 expression Moreover, PD-1 and PD-L1 expression significantly correlated with CD56 and FOXP3 expression. High intratumoral FOXP3 expression was significantly associated with disease relapse (P=0.029). CD4 and FOXP3 expression was significantly higher in CKS and CAS, as compared with HIV-KS. All in all, PD-1 and PD-L1 expression was relatively weak and did not significantly differ between CKS, HIV-KS, and CAS patients. Nevertheless, PD-1 was positive in 31.6% of CKS, 28.6% of HIV-KS, and 33.3% of CAS patients. PD-L1 was expressed in 36.6% of CKS, 28.6% of HIV-KS, and 41.7% of CAS patients. We have provided evidence that PD-1/PD-L1 signalling is of importance in angiosarcomas such as CKS, HIV-KS, and CAS. Our results support the notion that the use of PD-1/PD-L1 inhibitors may represent an effective strategy against these tumors.

Atypical presentation of classic Kaposi sarcoma in circumcised penis presenting as an ulcerative nodule with human herpesvirus 8 (HHV8) positivity and successfully treated with only local excision

IntroductionAlthough the Kaposi sarcoma (KS) is one of the AIDS defining entity and seen in almost one third of HIV infected patients with low CD4 cell counts, it is not uncommon in HIV seronegative persons, but genital KS is rare, particularly in people without risk factors for HIV infection. Isolated penile KS is an unusual manifestation, especially as solitary nodule with ulceration, in HIV seronegative patient.Case presentationWe report such a case of Kaposi sarcoma showing HHV-8 positivity in an elderly male Arabian patient with a delay in prompt diagnosis, but treated successfully with 3 3 years follow-up after limited local surgical excision.ConclusionThe general practitioners, venereologists and urologists should think of KS as a possibility in such lesion and consider early biopsy.

404O - A phase II single arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated Classical Kaposi Sarcoma (CKS)

BackgroundCKS is an angioproliferative mesenchymal neoplasm causatively associated with human herpes virus 8 infection. Though recombinant IFNa is approved for treatment of AIDS-related KS, data is limited regarding the role of immune modulation. Based on favorable responses in viral-induced cancers, we hypothesized that CTLA-4 and PD-1 blockade can induce tumor regression in CKS. We present pre-planned interim analysis of a phase II study of Nivo/Ipi in previously treated (tx) progressive CKS. MethodsCKS pts with progressive disease after > 1 line of systemic tx and measurable disease by PET/CT and/or physical exam received nivolumab 240mg d1,15,28 and ipilimumab 1mg/kg d1 q42 days until progression or toxicity. The primary endpoint (EP) was overall response rate (ORR), secondary EP include 6-months progression free survival rate (PFS) and safety. Exploratory EP included PD-L1/MMR IHC, DNAseq (596 genes)/RNAseq (whole transcriptome) of tissue and matched blood to explore CKS genomic traits and IO correlates: TMB, MSI, dMMR, PD-L1, immune gene expression (PD1, CTLA4, etc) (Tempus Labs, Chicago, IL, USA). ResultsTwelve patients were enrolled and evaluable between Apr2018-Jun2019 and 11 were evaluable for response. Median age 72 (61-81). At a mFU of 6 months ORR was 45% (4 pts PR, 1 pt CR, 6 pts SD). mPFS was not reached, 6-mo PFS rate was 91% (1 out of 11 patients had PD). The safety profile was as expected with three patients with G2 toxicity (1 ALT/AST increase, 1 asymptomatic lipase increase) and two patients with G3 toxicity (1 colitis, 1 asymptomatic lipase increase). One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in one pt (G2 LFT increase. maintaining CR 4 months after treatment discontinuation). Correlative results are available for four patients showing negative PDL1 IHC in all, low TMB, MS-S, but marked overexpression of CTLA4, PD1 and PDL1. ConclusionsThe interim analysis in this prospectively designed phase II study of nivo/ipi demonstrate promising activity in progressive CKS, with 45% ORR and a 6mo PFS rate of 91%. Toxicity profile as expected in this class of drugs. Correlative studies are preliminary but warrants further investigation into immune gene expression profiles. Clinical trial identificationNCT03219671. Legal entity responsible for the studyThe authors. FundingBMS Rabin Medical Center. DisclosureA. Zer: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AZ. All other authors have declared no conflicts of interest.

Cancer prevention and control: Kaposi's sarcoma.

Kaposi’s sarcoma (KS) is a vascular tumour of endothelial origin that is associated with human herpes virus-8 infection. In sub-Saharan Africa, AIDS-KS remains the most common HIV-associated malignancy, and hence it poses a huge burden to the already constrained health-care systems. KS has four clinical variants, namely, classic, endemic, iatrogenic and epidemic KS. The histopathology in these different KS forms is essentially identical; however, they have different clinical patterns. Expanding knowledge of KS biology increases hope for prevention, disease control, and hence better quality of life among patients. Primary prevention strategy for KS-associated herpes virus and management of disease complication, such as lymphoedema should be the focus of disease-prevention and -control research.

Candidate Predisposition Variants in Kaposi Sarcoma as Detected by Whole-Genome Sequencing.

Familial clustering of classic Kaposi sarcoma (CKS) is rare with, approximately 100 families reported to date. We studied 2 consanguineous families, 1 Iranian and 1 Israeli, with multiple cases of adult CKS and without overt underlying immunodeficiency. We performed genome-wide linkage analysis and whole-genome sequencing to discover the putative genetic cause for predisposition. A 9-kb homozygous intronic deletion in RP11-259O2.1 in the Iranian family and 2 homozygous variants, 1 in SCUBE2 and the other in CDHR5, in the Israeli family were identified as possible candidates. The presented variants provide a robust starting point for validation in independent samples.

A case of mistaken identity: classic Kaposi sarcoma misdiagnosed as a diabetic foot ulcer in an atypical patient

BackgroundThe presentation of Kaposi sarcoma is divided into four known clinical subtypes. In this case report we describe classic Kaposi sarcoma in an African-American heterosexual, diabetic, seronegative human immunodeficiency virus male. Classic Kaposi sarcoma is rare in this patient demographic and can be easily misdiagnosed.Case presentationThe patient presented with a lesion between the fourth and fifth digits of his right foot which was initially diagnosed as a diabetic foot ulcer. Despite local wound care, the lesion did not resolve. A shave biopsy was performed and histopathology findings were consistent with classic Kaposi sarcoma.ConclusionsThe patient tolerated local radiotherapy well and had complete resolution of his pedal lesion. There have been emerging associations between diabetes and Kaposi sarcoma. As such, clinicians should have a low threshold when considering the biopsy of suspicious pedal lesions in patients with diabetes. The utilization of appropriate biopsy technique may lead to the diagnosis of classic KS tumors in populations outside of the current four widely accepted clinical subtypes.

Kaposi sarcoma in Southern Finland (2006-2018).

Kaposi sarcoma (KS) age-standardized incidence rate is below 0.3 per 100,000 in Nordic countries. Data on KS in Finland have been sparse. A retrospective review of all the patients with KS cases managed in the Helsinki University Central Hospital between 2006 and 2018. Forty patients (median age at diagnosis 45years, 38 males) were included. About 2.5 new cases were diagnosed per year (incidence 0.16 /100,000). The different subtypes of KS were: human immunodeficiency virus (HIV) (65%), classical KS (30%), and immunodepression (5%). Patients with HIV were significantly younger, more likely to have cutaneous lesions of the face, the trunk, and mucosal lesions,and KS withinlymph nodes and inner organs. KS was diagnosed at the same time as HIV in 77% of cases, 28% with CD4-cell level above 300cells/mm3 . Among the patients with classical KS (n=12), 75% were of Finnish origin, 41% had a second primary malignancy diagnosed, and 25% had noninsulin dependent diabetes mellitus. Among HIV patients, 27% had another AIDS-related illness, 7% of the patients developed lymphoproliferative disorders, and 7% a hemophagocytic syndrome. Patients with HIV were always treated with antiviral therapy, with pegylated liposomal doxorubicin in 57% of the cases. Local radiotherapy was the main treatment for other KS types. None of the 5 deaths during follow-up was related to KS. Classical KS (KS-CLA) occurs among native Finns, frequently with other present malignancies. Screening of HIV and other malignancies is warranted in new cases of KS.

Atypical presentation of classic Kaposi's sarcoma

Atypical presentation of classic Kaposi's sarcoma

A phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated Classic Kaposi sarcoma (CKS).

11064 Background: CKS is an angioproliferative mesenchymal neoplasm causatively associated with human herpes virus 8 infection. Though recombinant IFNa is approved for treatment of AIDS-related KS, data is limited regarding the role of immune modulation in CKS therapy. Based on favorable responses in viral-induced cancers, we hypothesized that CTLA-4 and PD-1 blockade can induce tumor regression in CKS. We present pre-planned interim analysis of a phase II study of Nivo/Ipi in previously treated progressive CKS (NCT03219671). Methods: CKS pts with progressive disease after ≥ 1 line of systemic therapy and measurable disease by PET/CT and/or physical exam received nivolumab 240mg d1,15,28 and ipilimumab 1mg/kg d1 q42 days until progression or toxicity. The primary endpoint was overall response rate (ORR), secondary endpoints include 6-months progression free survival rate (PFS) and safety. Correlative studies in tumor and serum samples are ongoing using an NGS panel for DNA and RNA and proteomic staining (Tempus Labs Inc). A pre-planned interim analysis was conducted after the first ten enrolled patients for efficacy and toxicity evaluation. Results: Ten patients were enrolled and evaluable between April2018 and February2019. Median age 72 (61-79), all male. At a median FU of 3.1 months (1.5-8.1) ORR was 50% (4 patients PR, 1 patient CR, 5 patients SD). Median PFS was not reached however no progression of disease was documented so far. The safety profile was as expected with all patients experiencing G1 toxicity and four patients with G2 toxicity (1 ALT/AST increase, 2 asymptomatic lipase increase). One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in one patient (G2 LFT increase. maintaining CR 4 months after treatment discontinuation). Correlative results are pending. Conclusions: The interim analysis in this prospectively designed phase II study of nivolumab and low-dose ipilimumab demonstrate promising activity in progressive CKS, with 50% ORR and no events of progression thus far. We expect to report the updated efficacy and correlative data. Clinical trial information: NCT03219671.

Clinical features of Kaposi's sarcoma: experience from a Taiwanese medical center

Most of the previous reports regarding the clinical features of Kaposi's sarcoma (KS) have been performed in Western and African countries. The clinical characteristics of KS have not been well defined in Han Chinese or Taiwanese patients. In this study, we analyzed the clinical features of KS patients in a Taiwanese medical center. Medical records from Kaohsiung Medical University Hospital over the past 20 years (1996-2016) were comprehensively reviewed. There were 55 patients with KS (50 males and 5 females), including 37 patients (67%) with classic disease, 17 patients (31%) with AIDS-associated disease, and one patient (2%) with immunosuppressive medication-related disease. The average age was 58.7 years (range 20-87 years), and the average age was younger for AIDS patients (33.8 years) compared with non-AIDS patients (69.8 years). Among patients with classic KS, lesions were mostly localized to the lower extremities, whereas AIDS-associated KS patients were more likely to develop disseminated skin lesions, skin lesions on atypical sites (head and neck, trunk), and extracutaneous involvement (particularly oral cavity). The most common underlying diseases were diabetes mellitus (20% of patients) and hepatitis B (15% patients), and 38% of KS patients were smokers. Patients with AIDS-associated KS usually responded well to chemotherapy, whereas only 32% of patients with non-AIDS-associated KS showed complete response to radiotherapy. The findings of the current study will serve as important references for clinicians in the diagnosis of KS and may form the basis for the implementation of KS clinical practice guidelines in Taiwan.

Imiquimod 5% Cream Versus Cryotherapy in Classic Kaposi Sarcoma

Classic Kaposi sarcoma usually remains on the skin and has a slow progression; thus, local treatment methods are preferable. Imiquimod is an immunomodulatory agent with antiviral, antitumoural, and antiangiogenic properties that is expedient against Kaposi sarcoma. We aimed to clarify whether imiquimod is effective on classic Kaposi sarcoma lesions by comparing imiquimod treatment with cryotherapy, which is the most-used treatment method in our department for this disease. Patients with classic Kaposi sarcoma were included. All lesions of each patient were evaluated and measured by the blinded investigator considering infiltration and surface diameters. Then, lesions were categorized into 2 groups by the other investigator (nonblinded), and imiquimod 5% cream was administered 3 times per week without occlusion in 1 group. Cryotherapy was performed every 3 weeks in the other group. All lesions were reevaluated and measured at the end of 12 weeks by the blinded investigator. Initial and last measurements were compared between the treatment methods. Fifty lesions of 8 patients were included in this study. Imiquimod and cryotherapy were applied to 26 and 24 lesions, respectively. At the end of the study, statistically significant decreases were detected in all scores between weeks 0 and 12 with both treatment methods. Mean percentages of change in scores were not significantly different between the methods. Based on a limited number of patients and lesions treated, we believe imiquimod may be a suitable option to use for the treatment of classic Kaposi sarcoma.

K1 gene transformation activities in AIDS-related and classic type Kaposi\u2019s sarcoma: Correlation with clinical presentation

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi’s sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the different clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer.

Classic Kaposi's sarcoma with an initial solitary colon lesion.

Key Clinical MessageKaposi's sarcoma involving the digestive tract in isolated form before the appearance of diffuse skin lesions is very rare in HIV‐negative patients and is a condition requiring watchful waiting.