Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent inducers of interleukin (IL)-1β and IL-18 during inflammation, are large protein complexes typically consisting of a Nod-like receptor (NLR), the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific context. Here we summarize the role of different inflammasome complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro-inflammatory cytokines play in immunity.
Animals ; Carcinoma ; immunology ; pathology ; therapy ; Gastrointestinal Neoplasms ; immunology ; pathology ; therapy ; Humans ; Inflammasomes ; metabolism ; Melanoma ; immunology ; pathology ; therapy ; Neoplasms ; immunology ; pathology ; therapy ; Skin Neoplasms ; immunology ; pathology ; therapy

PURPOSE: Forkhead box p3 (Foxp3) positive T regulatory cells (Tregs) have a functionally immunosuppressive property that prevents effector cells from acting against self in autoimmune diseases or a tumor. It is known that Tregs may be highly relevant in cancer progression. Dendritic cells (DCs) induce cutaneous immune response, however several studies have suggested that DCs are involved in immunosuppression. The aim of this study is to evaluate the prevalence of Tregs and DCs infiltration in cutaneous premalignant and malignant squamous lesions. MATERIALS AND METHODS: We evaluated Tregs and DCs in skin tissue samples obtained from 83 patients with actinic keratosis, Bowen's disease or squamous cell carcinoma by immunohistochemistry. RESULTS: The prevalence of Tregs and DCs was significantly higher in squamous cell carcinoma and Bowen's disease than in actinic keratosis. In addition, the number of DCs was closely correlated with the prevalence of Tregs, and DCs were also located in direct proximity to Tregs. CONCLUSION: Tregs is related to cutaneous squamous tumor progression.
Bowen's Disease/immunology/metabolism/pathology ; Carcinoma, Squamous Cell/immunology/metabolism/pathology ; Dendritic Cells/immunology/metabolism/pathology ; Forkhead Transcription Factors/immunology/*metabolism ; Humans ; Immune Tolerance ; Keratosis, Actinic/immunology/metabolism/pathology ; Skin Neoplasms/*immunology/metabolism/pathology ; T-Lymphocytes, Regulatory/*immunology/metabolism/pathology

Aged, 80 and over ; Antibodies, Monoclonal ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Diagnosis, Differential ; Granuloma ; metabolism ; pathology ; Humans ; Keratins ; immunology ; Male ; Mucin-1 ; metabolism ; Skin Neoplasms ; metabolism ; pathology

Antigens, CD ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Killer Cells, Natural ; pathology ; Leg ; Lymphoma, T-Cell, Cutaneous ; immunology ; pathology ; Middle Aged ; Skin Neoplasms ; immunology ; pathology

OBJECTIVETo study the clinical and pathologic characteristics of poorly differentiated cutaneous angiosarcoma of scalp.

METHODSEight cases of poorly differentiated cutaneous angiosarcoma of scalp were enrolled into this study. The clinical manifestations and histopathologic features were analyzed. Immunohistochemical study for CD31, CD34, factor VIII-related antigen, vimentin, AE1/AE3, CAM5. 2, epithelial membrane antigen and carcinoembryonic antigen was performed.

RESULTSThe mean age of the patients was 69 years. The male-to-female ratio was 5 : 3. The tumor manifested clinically as bruise-like lesion in early phase, indurated erythematous plaque accompanied by nodules, ulcerations and bleeding in advanced phase. Histologically, the tumor was composed of solid sheets of undifferentiated spindle cells which were not easily recognizable as vascular in origin. Nuclear atypia was always present. The tumor cells in all of the 8 cases strongly expressed CD31, factor VIII-related antigen and vimentin. Weak expression of CD34, AE1/AE3 and CAMS. 2 was noted in 2, 4 and 4 cases, respectively. The staining for epithelial membrane antigen, carcinoembryonic antigen and S-100 was negative. Conclusions Angiosarcoma needs to be excluded by histologic examination whenever bruise-like and erythematous lesions occurring on scalp skin of elderly patients. The endothelial origin of the tumor cells can be confirmed with immunostaining for CD31, CD34 and factor VIII-related antigen.

Aged ; Aged, 80 and over ; Antigens, CD34 ; immunology ; Biomarkers, Tumor ; analysis ; Cell Adhesion Molecules ; Cell Differentiation ; Endothelium ; metabolism ; Female ; Hemangiosarcoma ; immunology ; Humans ; Male ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1 ; immunology ; Scalp ; pathology ; Skin Neoplasms ; immunology ; metabolism ; pathology ; Vimentin ; analysis

OBJECTIVETo investigate the correlations among Ki-67 expression, mitosis and other clinicopathological parameters of primary cutaneous malignant melanoma, and search for prognostic factors of malignant melanoma.

METHODSTotally 127 cases of primary cutaneous malignant melanoma were collected from Beijing Cancer Hospital. Immunohistochemical study for Ki-67 was performed, and the mitosis was calculated referring to "hot spot" method recommended by the seventh edition of the American Joint Committee on Cancer (AJCC) melanoma staging system. The correlations of Ki-67 expression, mitosis and other clinicopathological parameters were analyzed, and the survival analysis of all these risk factors including TNM and Clark level was conducted based on follow up data.

RESULTSThe expression level of Ki-67 was associated with necrosis and Breslow thickness (P < 0.05). Mitosis was correlated with Clark level and Ki-67 expression (P < 0.05). Univariate analysis indicated Ki-67 expression level (P = 0.043), mitosis (P = 0.030) and TNM stage (P < 0.001) might influence the survival of patients. However, multivariate analysis showed that the TNM staging was the only independent prognostic factor affecting survival.

CONCLUSIONSThe prognosis of patients with primary cutaneous malignant melanoma was closely related to the TNM staging at the fist examination. Ki-67 expression and mitosis are two important clinicopathological parameters of primary cutaneous malignant melanoma.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cell Proliferation ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Melanoma ; immunology ; pathology ; Middle Aged ; Mitosis ; Neoplasm Grading ; Neoplasm Staging ; Proportional Hazards Models ; Skin Neoplasms ; immunology ; pathology ; Survival Rate ; Young Adult

OBJECTIVETo study the clinicopathologic features and differential diagnosis of myxoid dermafibrosarcoma protuberans (DFSP).

METHODSThe clinical and pathologic features of 16 cases of myxoid DFSP were reviewed.

RESULTSThere were altogether 15 males and 1 female. The age of the patients ranged from 11 to 73 years (mean = 47 years and median = 48 years). The commonest site of involvement was trunk (number = 11), followed by shoulder (number = 2), head and neck (number = 2), and extremity (number = 1). Similar to conventional DFSP, most patients presented with a slowly enlarging subcutaneous nodule which showed a rapid recent growth in some cases. Amongst the 16 cases studied, 12 occurred de novo and 4 represented local recurrence. The tumors ranged from 2 to 10 cm in greatest dimension (mean = 5 cm and median = 4 cm). Histologically, they were poorly circumscribed and located in the dermis, with focal infiltration into the underlying subcutaneous tissue. Seven cases were purely myxoid and composed of spindly and stellate cells with delicate arborizing vascular meshwork. The remaining 9 cases were predominantly myxoid (> 50%), with 5 cases containing cellular areas resembling conventional DFSP and 4 cases showing fibrosarcomatous transformation. In addition, foci of giant cell fibroblastoma-like areas were noted in 1 case. Immunohistochemical study showed that the tumors cells were positive for CD34. The staining was weak in the myxoid areas, as compared with conventional DFSP. Of the 4 recurrent cases, one patient developed lung metastases.

CONCLUSIONSMyxoid DFSP represents a rare variant of DFSP and may pose important diagnostic pitfalls. It is especially so if the tumor purely consists of myxoid element. Familiarity with the histologic features helps to avoid misdiagnosis.

Abdominal Wall ; Adolescent ; Adult ; Aged ; Antigens, CD34 ; metabolism ; Child ; Dermatofibrosarcoma ; diagnostic imaging ; immunology ; pathology ; surgery ; Diagnosis, Differential ; Female ; Head and Neck Neoplasms ; diagnostic imaging ; immunology ; pathology ; surgery ; Humans ; Lung Neoplasms ; secondary ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Radiography ; Shoulder ; Skin Neoplasms ; diagnostic imaging ; immunology ; pathology ; surgery ; Young Adult

OBJECTIVETo study the clinicopathologic features, immunophenotype and prognosis of primary cutaneous anaplastic large cell lymphoma (C-ALCL).

METHODSEight cases of C-ALCL were enrolled into the study. The clinicopathologic features, immunohistochemical findings and results of in-situ hybridization for EBER 1/2 were analyzed.

RESULTSThree of the 8 patients were males and 5 were females. The median age was 49.5 years. C-ALCL often presented with solitary skin nodule, without systemic symptoms. Histologically, the lymphoma cells infiltrated the dermis and subcutis in a sheet-like pattern. They were of large size and showed conspicuous nuclear atypia. Immunohistochemical study showed that more than 75% of the lymphoma cells were positive for CD30. All cases expressed one to three T cell markers (CD3, CD5 or CD45RO) and cytotoxic granule-associated antigens (TIA-1, granzyme B or perforin). The staining for leukocyte common antigen was positive in all cases, while the expression of CD5, CD8, ALK-1 and epithelial membrane antigen was noted in 5, 1, 1 and 3 cases, respectively. The staining for CD15, CD20, CK and HMB45 was negative. In-situ hybridization for EBER 1/2 was also negative in all the cases studied. Follow-up information was available in 6 patients. Five of them were still alive and 1 died of unclear cause.

CONCLUSIONSC-ALCL has distinctive clinicopathologic and immunophenotypic features. It is not Epstein-Barr virus-related and often carries a favorable prognosis.

Adult ; Aged ; CD5 Antigens ; metabolism ; Child ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Immunophenotyping ; In Situ Hybridization ; Ki-1 Antigen ; metabolism ; Leukocyte Common Antigens ; metabolism ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; immunology ; metabolism ; pathology ; therapy ; Male ; Middle Aged ; Prognosis ; RNA, Viral ; metabolism ; Skin Neoplasms ; immunology ; metabolism ; pathology ; therapy ; Young Adult